Employee Relations †Trade Unions Essay

In the early days of capitalism employers, in their struggle for maximum profits, were able to act with almost complete ruthlessness in their treatment of workers. They could take advantage of every rise of unemployment or inflow of immigrant workers to reduce wages to a bare minimum, using the lock-out if necessary to starve workers into submission. They imposed excessive hours of labor and ordered temporary extensions of normal hours without giving overtime pay. They employed workers in overcrowded and unsanitary factories and workshops, and exposed them to frequent accidents from dangerous machinery. They introduced new working processes and machinery at will, often replacing men by lower-paid women and children. Factory discipline was like that of a military force, and workers who ‘mutinied’ could be sacked and, by arrangement with other employers, blacklisted, so that they could not get work elsewhere. Employers accepted no responsibility for payment of wages during sickness, and workers sacked or disabled had to rely on their own resources. Trade unions were formed to resist these pressures. The basic idea was that, by combining together, workers could get better terms, protect individuals against victimization and provide payments out of union funds during strikes or lockouts. As the immediate consequence of successful union action was to reduce the employers’ profits, their reaction was predictable and they did everything they could to crush the unions. They got the government and Parliament to declare the unions illegal for organizations under laws carrying savage penalties. They declared that British industry would be ruined by the unions and the workers would become unemployed. They had the backing of the church and of most economists in their anti-union campaign, yet so desperate was the condition of the workers that unions went on being formed and operating. Unable to suppress them the government finally, in 1824, made them legal. Employers have come to learn that trade unions can be useful to them. Now only a few employers and eccentric capitalists are anti-union. Most employers, especially the bigger ones, including the nationalized industries and the government, accept trade unions as â€Å"social partners† whose joint task it is to see that industry runs smoothly and with a minimum of industrial trouble. Employers have had to come to terms with trade unions and strikes. In return for recognition (sole bargaining rights, compulsory union membership and sometimes the deduction of dues from wages and representation on various joint committees) trade unions are expected to keep their members in order and, if necessary, discipline them: for example, if they interrupt production by going on unofficial strike. Most unions in Britain today are prepared to accept such a deal. The question arises to what extent modern trade unions can still be regarded as democratic organizations, in the sense of being run by and for the workers. That the unions do provide a service for their members cannot be denied. What is relevant in this context is the extent to which trade unions are run by their members. Most unions have formal democratic constitutions which provide for a wide degree of membership participation and democratic control. In practice however, these provisions are sometimes ineffective and actual control of many unions is in the hands of a well-entrenched full-time leadership. It is these leaders who frequently collaborate with the State and employers in the administration of capitalism; who get involved in supporting political parties and governments which act against the interest of the working class. But it would be wrong to write off the unions as anti-working-class organizations. The union has indeed tended to become an institution apart from its members; but the policy of a union is still influenced by the views of its members. A union is only as strong as its members. For without their participation at the place of work, and without their willingness to go on strike or take some other form of industrial action, a union would be in a weakened position with regard to the employer. Although the First International lasted for only a few years it left behind unions in many countries which appreciated the need for international organization, leading in 1901 to the formation of the International Federation of Trade Unions representing for each country national federations like the TUC. At the same time international organizations were formed representing unions in particular industries, such as the miners, the transport workers, engineering workers, etc. The statutory recognition rights provided by the Employment Relations Act 1999 appear to offer substantial new legal support for trade unions in Britain. It is, however, far from clear how substantial this support will prove to be in practice, or how far it will alter the extent and conduct of collective bargaining. There have already been some broad-ranging analyses in anticipation of the legislation (McCarthy, 1999; Wood & Godard, 1999; Towers, 1999). Although the law increasingly acknowledges alternative forms of employee representation, the promotion of collective bargaining through a recognized trade union is ‘still the favored means of advancing the interests of both unions and workers’ (McCarthy, 2000). There are inherent difficulties in using legal sanctions to bring parties to the bargaining table; the 1999 Act, accordingly, holds the threat of statutory recognition in reserve for situations where the parties have failed to make provision for voluntary recognition. This ‘procedural’ emphasis means that, on close inspection, what appears to be a statutory right to recognition is in fact nothing of the sort. The Act is therefore likely to disappoint those who see it as the harbinger of a new right to collective bargaining. The new recognition procedure arguably makes more sense as part of a wider package of measures aimed at advancing ‘partnership’ at work. However, this is not necessarily consistent with the priority given to the recognized trade union as the preferred model of employee representation. The problem is not simply that the new law will have little or no impact on workplaces where union influence, while significant, is nevertheless far below the membership thresholds set for statutory recognition. Even where the union can show majority support within the relevant bargaining unit, the new law does little to promote an active, continuing dialogue between the parties. This is in contrast to the alternative ‘information and consultation’ model of employee representation which is found in various forms in mainland Europe and which has enjoyed, from time to time, the support of the TUC. This approach arguably has the potential to promote partnership based on dialogue in many more workplaces than those which will be affected by the new recognition law, and, indirectly, to widen the range of matters over which bargaining takes place. A natural assumption might be that the act of trade union recognition is clear-cut. A reasonable starting point would be that it is comparable with other acts of legitimation or authorization of status such as the granting of citizenship, or the granting of diplomatic recognition to a foreign government. By such actions governments provide access to a range of rights which are in principle both defined and enforceable and, furthermore, relate to third parties. Employers, however, are very different from governments. The rights that they can grant to trade unions are solely with regard to transactions with themselves, and do not normally bind third parties. As a result, in the context of British labor law, the definition and enforcement of these rights is both more private and more problematic. This elusive character of recognition rights has increased with the decline of industrial agreements in Britain. Forty years ago, the granting of recognition to a union would, for the great majority of workplaces, imply at very least conformity with the appropriate industrial agreement. With this conformity would come not only substantive rights to such things as pay and hours minima, but also procedural rights to union representation, both in individual disciplinary procedures and in collective procedures to vary the agreements. Today, with a few exceptions (such as in the electrical contracting, construction, and knitwear industries) such agreements have largely disappeared. They now cover only a small proportion of the minority of British employees who are still covered by any sort of collective bargaining (Cully & Woodland, 1998). For nearly 70 per cent of all those covered by collective bargaining, and for over 80 per cent of all those covered within the private sector, bargaining is conducted not by sector or industry, but at the level of the individual enterprise, or of some subordinate part of it (Brown et al. 2000). Bargaining at the level of the enterprise does not necessarily precede on the basis of formally defined recognition rights. The law does not require a recognition agreement to be in writing. Formal acknowledgement of a union’s rights often amounts to little more than the specification of its role in a grievance or discipline procedure, or giving it a named role in consultation procedures. There may be no written document indicating that a union has negotiation rights on specified issues. Even where a union plays a substantial role of representation and bargaining within an enterprise, there may be few clues to such an entitlement from anything that has been written down. Whether or not anything is written down, the status granted to a union by an employer is not a black-and-white issue. It is, as we see further below, a matter of degree. The depth of trade union recognition granted by an employer depends, in part, upon the scope of bargaining, which is another way of describing the range of issues on which bargaining is permitted (Clegg, 1976). Other aspects of the depth of recognition include the employer’s predisposition to make concessions during collective bargaining, the facilities that are offered to trade unions, the extent to which the bargaining relationship is formalized, and the extent to which the employer communicates with employees other than through union channels. The mere fact that an employer has granted union recognition tells one little about the practical value of that to the trade union in terms of effective collective bargaining. There are various legal concepts of recognition, the meanings of which depend on the purpose they are meant to serve. Recognition may be a passport not just to collective bargaining but to certain statutory rights. If an employer voluntarily recognizes a union, it comes under a statutory obligation to consult representatives of that union before making certain redundancies; where there is a transfer of the undertaking; before contracting-out of the state earnings-related pension scheme; and in relation to health and safety matters (Deakin & Morris, 2001). Recognition also entitles the union to claim disclosure of information for collective bargaining purposes, and entitles union members to time off for certain activities. In these contexts, ‘recognition’ refers to ‘the recognition of the union by an employer, or two or more associated employers, to any extent, for the purposes of collective bargaining’. Collective bargaining is defined as ‘negotiations relating to or connected with’ a range of matters grouped under seven categories and including, inter alia, terms and conditions of employment; the physical conditions of work; engagement; termination; allocation of work; discipline; trade union membership; trade union facilities; and machinery for negotiation or consultation (Trade Union and Labour Relations (Consolidation) Act 1992, s. 78). It is sufficient that the employer negotiated with a union on any one of these matters for the union to be recognized in this sense. With the passage of the 1999 Act, an additional definition of recognition was needed, one which would identify those matters over which the employer would have a duty to bargain. Essentially, this means that the scope of matters over which statutory recognition arises are narrower than the range of matters which the law associates with the practice of voluntary recognition. Thus, the nature of the power relationship between the employer and the trade union will continue to be highly relevant in determining the scope and extent of bargaining, just as it was prior to the coming into force of the new procedure. There are several other respects in which the new statutory right to recognition is tightly circumscribed. In particular, an application for statutory recognition can only be lodged in respect of bargaining units over which there is not, already, a voluntary recognition agreement. More specifically, a union which is, itself, already recognized over any one of ‘pay, hours or holidays’ (emphasis added) (Trade Union and Labour Relations (Consolidation) Act 1992, Sched. A1, para. 35(2) (b)) is apparently barred from bringing a claim for statutory recognition in respect of the relevant bargaining unit. Nor can a union use the statutory procedures to challenge a rival, incumbent union, unless that union is non-independent, and even then, the procedure for statutory derecognition is highly complex (Trade Union and Labour Relations (Consolidation) Act 1992, Sched.  A1, Part VI). At first sight, the new procedure enshrines a right to recognition over pay, hours and holidays for unions which can show that they have majority support in the relevant bargaining unit. On closer inspection, this right is far from universal since it only arises in respect of bargaining units where either no union is recognized or where the matters over which recognition has been conceded do not cover any part of the statutory core of ‘pay, hours and holidays’. Moreover, it is in essence a right to invoke a procedure rather than a right to achieve a particular outcome. An employer can avoid the imposition of a statutory order by making a voluntary agreement at one of a number of stages within the recognition procedure. If this occurs, the union can hold out for bargaining over the statutory core, knowing that, if it can show majority support in a ballot or otherwise, the CAC must grant it a declaration of statutory recognition. However, the content of statutory recognition is then dependent on the remedies which are made available against a recalcitrant employer.

Religious Ethics Essay

In this essay, I will be taking religious ethics to mean the ethical principles of Christianity, i.e. Christian Ethics. This includes the moral decisions based on the teachings of Christianity from such sources as the Bible. The term ‘environmental issues’ covers a broad spectrum of concerns. As far as ethics is concerned, the issue is how far our moral concerns should extend to the environment and how we should live out our responsibility towards it. By environment, the earth and all its living entities are concerned. As our concern for the environment has increased and our general awareness heightened, debates about morality towards the environment have emerged. Issues such as climate change, pollution, global warming and the extinction of species can all be linked to the actions of humans (e.g. CFCs and the burning of fossil fuels). Therefore, as the damage to our environment becomes more problematic, the link between its deterioration and the actions of humans becomes more prominent. Anthropocenctrism, usually attributed to the teachings of Christianity, places humans at the centre of the world and therefore the environment. Aristotle taught that ‘nature has made all things specifically for the sake of man’; he basically states that humans are the only beings on earth that have intrinsic value, and that everything else placed on this earth has instrumental value and is to be used for the benefit of humans. Humanity is placed at the top of Aristotle’s hierarchy due to their possession of reason; animals can move and feel pain so come next; plants who can only grow and reproduce are placed at the bottom; and he appears to place no value on inanimate objects as they don’t even have a vegetative soul. During the late 18th century and the early 19th century, the thinkers of the enlightenment period, also known as ‘the age of reason’, emphasised anthropocentric approaches and concluded that reason is the mark of authority. Scientific discoveries were made that bred confidence in man’s ability and shifted philosophical thought away from the teaching that God and the church are the centre of morality. Capitalism emerged which taught emphasising the success of the individual. Immanuel Kant placed humans at the top of his hierarchy with their intrinsic worth due to their possession of reason. Kant also viewed animals as of no moral concern to humans; the only time it is wrong to hurt an animal is when it could instrumentally harm a human. However, by Kant’s reasoning that we can only have concern for animals if the impact is on humanity, he is contradicting himself as he looks to the consequence, which denotes it as a hypothetical imperative and therefore immoral. He also decides on moral action using formulations of the categorical imperative; 1. universalisability, where no contradictions can occur. Kant did not intend his theory to be used as an environmental ethic as it was not relevant at the time. 2. Kant declares that only moral rational agents need moral consideration as ‘ends in themselves’ and we should exclude animals from moral worth which concludes it to be outdates and unsuitable to be used as an environmental ethic. Therefore, Kant’s ethic is likely to be an unsympathetic approach and would probably lead to damage to the environment. Christian anthropocentrism is mainly derived from the teachings of Genesis. The creation story (Genesis (1:26-28) teaches us to â€Å"fill the earth and subdue it; and have dominion over the fish of the sea and over the birds of the air and over every living thing that moves upon the earth†. This implies that God has made all things for the sake of humans; that the only beings upon this earth that have intrinsic value are humans, and that everything else serves to benefit humanity (instrumental value). The only reason we need to have care for the environment is because our actions may have an impact, sooner or later, upon ourselves. St Thomas Aquinas also held this belief and stated that â€Å"injury to an animals leads to the temporal hurt of man, either the doer of the deed, or of another†. Dr Lynn White suggested that we need to re-examine our attitudes towards nature, which derive from our religious beliefs, in order to successfully address the ecological crises. He said â€Å"Human ecology is deeply conditioned by beliefs about our nature and destiny – that is, by religion†. He develops this suggesting that our destruction and damage to the environment can be traced to the technological advances of the industrial revolution and the enlightenment period which are a result of the despotic interpretation of the Judeo-Christian teachings declaring Western Christianity as â€Å"the most anthropocentric religion the world has seen†. Utilitarianism is another approach towards ecological issues that one can consider when deciding the best approach towards environmental issues. Peter Singer is a preference utilitarian, who doesn’t measure happiness in the measure of extent or duration of happiness but instead on the satisfaction of desires or preferences. Singer measures the importance of an individual or being, not on their possession of a soul or reason, but on their ability to suffer. To Singer, it doesn’t matter whether the being in question is human or not and both humans and sensory non-humans are equally entitled to moral concern. As we can imagine that their preference would be to avoid pain. He accused many moral philosophers and scientists of Speceism; refusing respect to the lives of other species, not just humans, and proposed that we need to include animals in the ‘expanding circle of moral worth’; â€Å"If possessing a higher intelligence does not entitle one human to use another for his own ends, how can it entitle humans to exploit non humans for the same purpose?†. The problem that arises from Singer’s theory is whether or not plants, and lesser life forms and non-life forms are included in the ‘expanding circle of moral worth’ as they are not conscious living entities so we don’t know what their preferences would be. Initially, Singer does not consider lesser life forms to have any moral significance, but in the second edition of his book states â€Å"the argument from intrinsic value of the plants, species or eco systems is at best problematic†. Singer’s utilitarian argument has weaknesses in so far as it has no clear boundaries as to where our moral concern should lie. Unlike Christianity’s anthropocentric approach which clearly places humanity as the centre of our moral concern, Utilitarianism only beholds vague ideas of where our moral concern should extend to. The utilitarian argument has its strength in its positioning of the capability of suffering above the possession of reason. This does bear a more sympathetic approach towards humans of lesser intelligence (i.e. those with special needs) but then suggests that they are on the same level as animals. This would suggest Christianity to be a better approach as it is more compassionate. Biocentrism, proposed by Paul Taylor, extends the circle of moral worth to include all living things and thus declares that humanity is not the centre of existence. Taylor argues that all life forms have intrinsic value which human beings have a duty to respect. We therefore have a moral responsibility towards them which would entail engaging in practices and policies aimed at specific ways of preserving the ecosystems. Taylor holds non-living things such as mountains to only hold instrumental value and therefore they bare no ethical status. Taylor’s argument is fairly balanced as it doesn’t presume that human beings are the only beings with intrinsic value but he fails to introduce any sort of hierarchy and places humans on the same level as bacteria, which seems absurd. He also implies that we should all be vegans, but fails to address this, and doesn’t consider whether a lion is acting immorally if it eats a zebra. Christianity therefore is more logical as it sets a clear hierarchy which allows mowing the lawn and eating meat. Ecocentrism is another approach to environmental issues. It recognises the importance of the ecosphere and the environment with out suggesting that any organism as more important than the other. Aldo Leopold proposed an ecocentric theory; ‘The Land Ethic’ which â€Å"simply enlarges the boundaries of the community to include soil, waters, plants and animals. Or collectively – the land†. He argued that current conservation policies are based on economic motives. He says â€Å"it is inconceivable to me than an ethical relation to land can exist without love, respect, and admiration for land and a high regard for its value. By value, I of course mean something far broader than mere economic value; I mean value in the philosophical sense†. He argues that Christianity’s teachings of ‘dominion’ saw us as conquerors of the land and that if we are to resolve the ecological crises we need to see ourselves as members of the community that also includes the land. Another ecocentric approach is that of ‘deep ecology’ devised by Arne Naess. It was born out of appreciation for non-Christian religions that recognised the sacredness of natural phenomena. This includes the notion of ‘biospheric egalitarianism’ which views that all living things have intrinsic value. Deep ecology views the world as a network of interconnected and interdependent phenomena; a ‘web of life’. These theories fail to determine how lesser life forms could have any moral interest, and how mountains and the like could have any moral interests whatsoever. This weakens it as Christianity. However it does appear to be more sympathetic as it concludes that other life forms have intrinsic value, not just humans. Another ecocentric approach is that of the Gaia Hypothesis proposed by James Lovelock. After discovering that it is the earth’s unique atmosphere that makes life on earth possible, he declared the difference between earth and the other planets was ‘Gaia’. All life forms are part of ‘Gaia’ and he saw the earth as a self regulating living system. In his words Gaia is â€Å"a complex entity involving the Earth’s biosphere, atmosphere, oceans and soil; the totality constituting a feedback or cybernetic system which seeks an optimal physical and chemical environment for life on this planet†. He saw the ecosystems of the earth as intelligently organised, not by God, but by Gaia’s self engineering. He concludes that if humans were taken out of Gaia, it would survive without us; therefore, humanity is not integral to the environment. Lovelock later suggested that as the environmental issues increase, the planet may not be able to recover and we are in the process of killing the earth, which he refers to as matricide. This suggestion that the earth is intelligently organised has much evidence (for example the water cycle, the reproductive system). However, by suggesting that the earth is alive and therefore self regulates these systems is weak as it is hard to prove. For Christians, the intelligent organisation is of course a result of God. The despotic readings of the creation story present Christianity negatively as White argues. Because we are made in the image of God we believe that the world was made for our sake only. However, one must look at other interpretations of Christian teachings that would suggest a more considerate approach to the environment. One could interpret the use of the word ‘dominion’ no as despotic, but as a call for stewardship. God has chosen humanity to regulate the response of the natural world to its creator so we must care and conserve and acts as the director of nature’s obedience to God. This makes Christian teaching more ‘theocentric’ than ‘anthropocentric’ as it suggests that the peak of creation is God. If we used this as a basic principle when approaching environmental issues, then it would be a strong theory, as it allows humanity to care for the land. Aquinas’s Natural Law theory is based on the thinking of Aristotle, that all things in nature are for the good of man. He extends this further to explain how things are not worthless, but valuable because they are what God intended them to be; they fulfil their own Telos. Humans are declared as the most valuable beings due to their creation in ‘imago dei’ and possession of reason but we should follow stewardship rather than despotism. This would however suggest that despite the strengths of being stewards, being a Christian Ethic, one must have a belief in God to conclude this to be a valid approach to environmental issues. Another Christian approach is Joseph Fletcher’s Situation Ethics which emphasises the importance of love in moral decisions, but was never considered an environmental ethic. Fletcher believed in ‘personalism’; that people are placed before the laws, again being anthropocentric in that we are suggested to be able to do what we want. He promoted ‘pragmatism’; that one must do something that would produced the most loving consequences in that situation. This would be a positive approach to the environment as people would be loving towards it. This could perhaps places the environment second to human needs which would be a negative attitude. However, Fletcher’s ethic is too vague to be considered in any depth as we can’t define what is the most loving thing, who it’s for or even what ‘love’ means. Attfield suggests a deeper interpretation of Christian teachings in order to accurately devise an ethical basis towards the environment. He saw that in Job (38:25) for example, God is said to send rain for the plants and uninhabited wilderness. And to have made wilderness for the Ass. Also the proverbs inform us that â€Å"a righteous man regardeth the life of his beast†. This would be the understanding that Jesus would have had, following the Old Testament teachings. There are New Testament teachings that would instruct a more sympathetic attitude to nature such as Jesus’ time in the desert amongst wild beasts after his baptism, and the use of nature and animals in his teachings and parables. However, there are the passages of the Gadarene swine and the cursing of the fig tree that suggest a more inconsiderate attitude is permitted. In Hebrew tradition, Kings were answerable to God, not absolute monarchs in themselves, therefore according to Attfield â€Å"the biblical dominion of man is no despotism†. However, White argues that in medieval times the embrace of Christianity and the rejection of paganism changed the relationship between man and nature. The pagan ideas of living beings having a soul or a spirit (animism) encouraged a positive attitude towards nature, which were corrupted by the growth of Christianity. Attfield however counter argues these claims and says the ecological crises can’t be blamed on ancient traditions as they have happened in more recent times (post 1945). Japan, for example, which is not a Christian country, shares many of the environmental problems that the West has. It is not just paganism and Buddhism that impose a limit on humankind’s use of nature. Attfield then concludes that we needn’t have a new environmental position; we just need to revert to stewardship rather than dominion. Walter H O’Briant proposed a ‘born again Christian’ belief in the rapture; that Christ will return and the bodies and souls of the saved will go to heaven. The earth is, according to O’Briant, a temporary home therefore it doesn’t matter what we do to the earth. After considering the theories discussed and evaluating their strengths and weaknesses I would argue that religious ethics are the best approach to environmental issues, provided we revert to a more ‘stewardship’ attitude, rather than the despotic interpretation.

Upcoming Technological Advances in Nursing Case Study

Upcoming Technological Advances in Nursing - Case Study Example With all these related advances in technology, the professional culture of reflection, profound inquiries, and inter-professional collaborations will gear nursing as a whole towards success by the year 2025. Therefore, the whole field of nursing will be admirable and appreciable by many as patients will also enjoy the technology by getting the knowhow about various diseases, symptoms, causes and effects, drugs and methods of prevention and curing the diseases. Nurses too will enjoy many privileges and favors around. Technology has proven to every fundamental in the health care as a lot is being experienced in nursing. At work, nurses employ technology during care as long as they are within the clinical settings. Such settings where they can employ technology include; primary care, community, acute care, and long-term care so as to improve and come up with their clinical decisions and employ the most viable outcomes for clients they deal with (Huston, 2013). Another great change as far as technology is concerned is the health and wellness records of clients and family. Through technology, they are made to be in a position of reviewing and contributing positively to their health records, hence taking charge of anything that come about with relation to their wellbeing. Technology is very paramount within the nursing fraternity. When we talk about technology, automation comes in whereby computers and other machines are used in nearly everything that takes place. From the year 2025 and beyond a lot would have taken place technologically. Benefits will be experienced in staffing offices, census control, patient care, and determination of patient’s acuity.

Assignment Example | Topics and Well Written Essays - 250 words - 380

Assignment Example The thesis has been supported with examples of policies that have been implemented by the government. For example, the government has restricted insurance companies from charging premium prices to the obese people and this is not motivating people to eat healthy. The author is trying to argue against government’s present steps to fight obesity, but the article fails to persuade me because it lacks factual information and only focuses on providing emotional and opinion based information. The article titled as â€Å"Escape From The Western Diet† was authored by Michael Pollan and in this article the author argues that the Western Diet is the main cause of obesity and people should start eating the same way their ancestors used to. The author argues that the causes of obesity that have been identified by researchers are not real and are motivated by personal gains. The thesis of the article is that the western diet is the main cause of obesity and not the individual ingredients in the western diet (Graff 421). The author does not explicitly state the thesis and instead develops it over time. The author is trying to persuade the readers that it is time to change their diet plans and instead of eating a western diet, citizens of US should move back to eating what the ancestors used to consume. In order to pursued the readers, the author has quite well used the ethical appeals of ethos and pathos but the article lacks logos which includes factual information and thus the article lacks

BHS 499 (Senior Capstone Project) Module 1 SLP Essay

BHS 499 (Senior Capstone Project) Module 1 SLP - Essay Example through eliminating healthcare acquired infections and other avoidable accidents. National Health Services (NHS) formulated the Quality Framework in order to achieve the more improve quality of care at the same time support local clinical teams that consist the following: (1) Bring lucidity to quality in terms of access to evidences on best practice; (2) Publication of quality information to make it available to the public; (3) Offering rewards to high quality care givers; (4) Safeguarding basic standards in healthcare setting; (5) Ensuring state-of-the-art medical advances and service design; (6) Distinguishing the role of clinicians as leaders in quality of care (Davis, 2005; p1 par 1). warning systems in therapeutic procedures for cures of progressive diseases such as cystic fibrosis, diseases like cancer and heart disease, implantation procedures of artificial hips and kidneys. Nanoparticles may be very useful to researchers to overcome problems in gene therapy, and treatment of genetically inherited diseases. .Nanoparticles generally used to apply heat to cancer cells so they will be killed.

Intercultural Experience Assignment Essay Example | Topics and Well Written Essays - 1000 words

Intercultural Experience Assignment - Essay Example There are many different subcultures among the Latino population. I decided to try food from restaurant owned and managed by people from the island of Puerto Rico. Puerto Rico is an island located in the Caribbean region. The entire populations of Puerto Rico are actually U.S. citizens due to the fact that Puerto Rico is a territory of the Unites States. Officially the island’s government has a commonwealth political status with the United States. When I entered the restaurant I was greeting by a very nice woman who gave a greeting in Spanish. She was in Spanish â€Å"Bienvenidos a nuestro restaurant† which means welcome to our restaurant. I was given the menu within five minutes of my entrance. When the waitress gave me the menu she also brought some vegetables, bread, and water. I told the waitress that I was very hungry, but I did not know what to order due to the fact that I had never eaten puertorican food before. I explained to her that I was visiting their establ ishment as part of a class project in which I had to evaluate the food that I ate from an international location. She told me that I was very lucky because I had picked the right place to enjoy an exotic meal. The meal that I ended up ordering is called in Spanish â€Å"Mofongo con carne frita y caldo† which can translate to fried plantain with fried pork meat and fish or chicken stew. The meal was amazing. The fried plantain was the best part of the meal. It tasted absolutely delicious. Since the plantain it’s a bit hard it has to be dripped with the stew to make it softer to eat. The fried pork meat is a tremendous compliment to the plantain. The food was great and the price was right on the money. The meal only costs me $9.95 plus taxes and tip and it included the drink. I gave the waitress a $5 tip which represents a 50% tip for her services. Now that I had visited and eaten a unique cuisine meal from the Puertorican culture it was time for me to learn more about P uerto Rico. To achieve this task I decided to interview and old friend of mine who was born in Puerto Rico. In the following three paragraphs I am going to describe the different things I learned about the Puertorican culture based on my interview. Puerto Rico is a small island in the Caribbean Sea whose dimensions are 100 miles in length by 35 miles in width. The island with a population of 4 million inhabitants is considered one of the most populated regions in the world per square miles. The United States won a war with the Spaniard in 1898 which gave them control of Puerto Rico. Ever since 1917 the people of Puerto Rico have been US citizens. Puertorican have sacrificed a lot over the years with thousands of military solders being recruited from Puerto Rico. The official language of Puerto Rico is Spanish, but English is taught since elementary school to all the children. The educational system provides school for 12 years with the bilingual teaching of English. Most young adult s after finishing high school go to college. The college participation among the youth in Puerto Rico is higher than in the United States. A college education in Puerto Rico is much cheaper than in the United States. Puerto Rico imports that majority of its consumer products from the United States. The US marine is used to import merchandise into the United States. The Unites States and Puerto Rico shared a common military. The official currency of Puerto Rico is the US dollar. The island is poor in comparison with the United States with an income per capital of approximately $17,000 which

Employee Performance Appraisal Systems Essay Example | Topics and Well Written Essays - 3250 words

Employee Performance Appraisal Systems - Essay Example This essay declares that there are various benefits of these techniques; however, they are not without some limitations. Below, the paper is going to highlight the importance of employee appraisals, the reason why they are important, the benefits and banes of performance appraisals and more importantly, the legal implication of employee appraisals wrapping up the paper with a conclusive statement. This paper makes a conclusion that there are various researches conducted on the subject of employee performance appraisal. The basic concept is that employee appraisal has always been considered the task of the employer rather than considering in the element of a 360 degree evaluation. A 360 degree appraisal has several benefits that can be summed by saying that the evaluation works on all levels and provides a more comprehensive, well rounded approach to performance appraisals. Some researchers propose that self appraisals be made part of the appraisal process to evaluate work performance. Self appraisals however, are also studied to be more lenient, less variable and less discriminant with less halo effect as well. This is probably because the employee knows the amount of work they have done, how much effort they have put in, but leniency arises when employees consider themselves on an easier scale and project themselves positively than normal. However, problem areas of self appra isals become magnified in areas where decision making capability needs to be evaluated, along with identifying training need and applied criteria of elevation in terms of tasks and processes. (Murphy and Margulies, 1980) The research also points out that employee self appraisal is a method that falls in the same category as employer appraisal as it helps develop the employee's motivation and helps him or her participate in management. Murphy

Safety management Assignment Example | Topics and Well Written Essays - 750 words - 1

Safety management - Assignment Example Directing is a function of management that involves leadership. The people chosen to perform particular tasks need supervision and direction on how to perform their duties. The management of an organization does this supervision and leadership through directing. It involves more than merely giving directions to one’s juniors on what to do. The directing duty also involves motivating one’s team members to perform optimum towards achieving the set goals and objectives. Staffing, on the other hand involves assessing and evaluating of suitable individuals to take over positions in an organization, and placing them in the positions they most qualify to serve. The management determines the requirements of the job, makes advertisements on the available vacancies and takes the responsibility to hire the best candidate. This is usually after interviews. Thereafter, the management does orientation of the new staff member, trains him and places him. It also involves checking the progress of the new employee as far as performance of his duties is concerned. Controlling involves determining whether or not the resources available for operations of a company are used effectively. It has a close link with planning since it entails checking if the allocated resources have been utilized properly. Tools such as auditing could be employed to control the use of resources in an organization. 2) Safety incentive programs are essential in ensuring organizations are lured into practicing safe methods of production. This is essentially important in the manufacturing industry that produces a lot of wastes in form of gases and solid debris. Incentives that promote the use of methods that reduce production of poisonous gases are necessary to reduce illnesses and environmental degradation. Although the overall burden is borne by the tax payers who have to pay more to cover for the incentives, the

Porters 5 Forces Essay Example for Free

Porters 5 Forces Essay 1) New Business / Threat of New Entrants Changing Conditions in PESTEL, Product, Service differences, brand identity, access to distribution, necessary resources, learning curve, inertia of existing markets. Expected retaliation, switching requirements, scale economics and experiences. Capital requirements. Example: Upcoming smartphone known as the OnePlus One from a completely new firm. Cheaper than other firms such as Samsung, Apple and HTC but the quality is just as good, if not better. http://www.cnet.com//oneplus-one-to-hit-general/ 2 + 3) Bargaining Power of Suppliers and Customers Concentration Number of Buyers, Switching costs esp Relationships, Control of information, Forward and backward integration, threat of Vertical integration, availability of substitutes. Importance to others performance. Brand identity, marketing and purchasing incentives. Alliances, relationships and expectations. The ability of suppliers to change the firms performance. Eg Samsung has increased costs now that their suppliers went on strike. http://www.clb.org.hk//workers-samsung-supplier-china Likewise the same thing refers to consumers, but I cant of an example off the top of my head. 4) Threat of Substitutes Sideways competition, Comparative price/performance, backing by rich competitor. Comparative technological life cycle. Benefits no product features. Theres tons of substitute products in the smartphone industry of all ranges in price and quality, so that one is self explanatory. 5) Rivalry amongst Competitors Aside from the other four forces, the nature of rivals also determine the intensity and degree of rivalry. Competitors with different values, vision,  mission, strategy and operational effectiveness, combined with different perceptions and abilities of their senior managers will influence not only the degree of competition but also its patterns. The intensity of competition is also elevated when; there are severally equally strong players such as Samsung vs Apple Few chances for differentiation They all know whats coming up and they all copy each other. Galaxy Gear, Moto 360, Apple iWatch (Rumored)

Operation Management Essay Example for Free

Operation Management Essay 1.Operation Management For the success of an organization, the management crew plays a major role. An organizational structure is based on different operational parameters and in order to perform all the operations, it is mandatory to scrutinize every major aspect related to the organizational strategy. Keeping the significance of operation management under consideration, different authors have developed different concepts and hence promulgated all of them in order to indicate all the major aspects that can define what the operation management is and how it helps an organization in achieving high level of success. This paper is basically about how proper operation management helps an organization in performing different tasks strategically. For this purpose, the analysis is done from different perspectives. The first part of the paper gives an overview of what is operation management and for this purpose; different definitions promulgated by different authors have been cited as evidence. The second part of the paper throws light upon the role of an operational manager and what strategic efforts enables him to perform his duty effectively. The third part of the paper identifies the relationship of operation management with other core functions and for this purpose, the case studies of Heathrow International Airport and Nestlà © UK Chocolate Factory have been elaborated. Hence, the entire paper indicates how effective operation management affects the progress graph of the company in one way or other. However, before elaborating how the manager performs  his job, it is mandatory to throw 1.1.Definition of operation management Operation management can be considered as one of the most significant factors responsible for any country’s economic growth. As service sector has observed mass development and changes, the very concept of operation management emerged with a focus on economic efficacy in manufacturing. The traditional concept of manufacturing was otherwise limited to concept of production management only. The manufacturing capabilities have been advanced through innovative procedures and techniques, new materials and facilities as numerous challenges and opportunities have been posed by rapid development in technology sector. It thus gave rise to development and management of a service system which could effectively resolve major challenges for global competitive environment (Heizer, Jay H. and Render, Barry, 2008). Around the world, operation management has now been considered as major business procedure for productivity and improvement. Organisations have become more vigilant in acquiring operation management procedures and techniques to achieve their objectives with minimum resources and efforts. (R. Pannerselvam, 2004) defined operation management as a system which an organisation employs within its framework to transform a wide range of inputs into the desired outputs (services) by achieving its requisite level of quality. Operation management transforms by combining several resources which are being used in organisation’s operation subsystem into value added products and services. Undoubtedly this has to be a controlled process and it should follow the policies of organisation, therefore the whole concept of operation management works as integrated and interrelated management activities. These management activities are sometimes limited to manufacturing of certain products which is called production management, but when the same idea is extended to effective service management, then resultant sum of manag ement procedures is called as operation management. Resources, transformation, systems and value addition activities are some key factors which represents a broader picture of operation management within an organisation. Resources are material, capital and human inputs to the process of production. Material resources include materials and physical facilities such as inventories, supplies and plant equipment etc. capital resources include bonds, stock and/or taxes which can  be used to regulate flow of associated resources. Human resource is sum of intellectual capabilities of managers, technical and non-technical staff and is considered as most vital asset of the organisation. Transformation is basically the process of combining resources for obtaining higher value goods and services than original inputs under controlled conditions. Systems depict an arrangement of multiple components developed to obtain require objectives of the plan. Business systems contain personal, finance, engineering and operation, functioning altogether for integrity of organisation. Value addition activities ensure to increase organisations’ productivity ratio and give more value to the products (Waters, C. D. J. (1991). After reviewing different definitions promulgated by different experts, the next part of the paper will analyze the role of an operational manager in an organization. 1.2.The role of Operation Manager Operation managers of any organisation are concerned with planning, systemizing and controlling the action which impact human behaviour with the help of models. Planning helps in establishing action plan for the organisation and provide future-decision making. It is thus duty of operation manager to define the objectives and goals for the operations and it’s subsystems of the organisation. They need to design procedures and policies in order to achieve those objectives. This stage embraces the clarification of role and focus of certain operations into organisation’s overall strategy. Product and services planning conversion process and facility designing are also included in the planning. The establishment of authority and tasks and other related activities fall under the head of organizing. The flow of information and structure of roles are being established by the operation managers within operation subsystems. It is their responsibility to determine the attributes es sential for goals achievement and they need to assign the responsibility and authority to carry them out (Joseph, G. Monks, 2004). Other prime responsibilities of operation managers include transforming inputs into the outputs. To devise an effective production plan, say, which employs capacity, knowledge of production facility and materials is prime responsibility of an operation manager. They are supposed to schedule and control the system demands in order to retain require services and/or produce desired goods. They need to  evaluate quality inventory levels, cost etc. to maintain the quality associated with goods and services. They are obliged to regulation of systems and resources within the organisation thus maintaining transformation and effective value addition activities. Operation managers are required to observe parameters which may affect the human behaviors. They need to evaluate models and frameworks of an effective operation management within an organisation (Slack et al). As operation management is primarily concerned with the accomplishment of both resource utilization and satisfactory customer services, operation managers are supposed to maximize both and maintain an overall satisfactory performance of the organisation. Sometimes there is improvement in customer satisfaction while deterioration in resource utilization. To overcome any such activity, operation managers are trained to tackle such conflicts and they need to find and implement a balance for the organisation in order to achieve its basic objectives. The principle customer service objective is strongly dependent upon services of an en enthusiastic and able operation manager (S. Anil Kumar, N. Suresh, 2008). The next part of the paper will discuss the relationship of operation management with the core functionalities of the organization. 1.3.Relationship of operation management with other core functions One of the most significant functions that operation management plays in an organisation that it defines the ways for strategic planning of an organisation. As strategic planning is concerned with organisation’s decisions and remedies for certain environmental and business conditions, operation management provides road map for strategic planning for the organisation and eases the way with help of fundamental concepts. The scope of operation management is not limited to transformation of inputs into the outputs by utilising physical resources thus achieving successful customer satisfaction along with efficiency, development and adoptability for the organisation, but it is deeply associated with other core functions of an organisation such as marketing, finance, personnel etc. It also include product design, quality control, maintenance management, location of  facilities, materials management, planning and product control, process design and many other core and support functions. The modern concept of operation management is very dynamic and promising and it evidently brings outstanding results for an organisation working under controlled environment (Dilworth, James B., 1999). 2.Case Studies Following are two cases studies that indicate how proper operation management strategy helps the organization in achieving its ultimate objectives. In this regard, the Heathrow International Airport and Nestle UK Chocolate Factory have been taken a evidence. 2.1.Heathrow International Airport Heathrow International Airport is the UK’s only hub airport. Around 5,500 people have been employed by the BAA at Heathrow of which 25% employees perform operational, customer service and maintenance roles. Other 75% are in security and head office functions. In addition, BAA has some 65% interest and it operates the Naples Airport. These figures show the need and significance of operation management within framework of Heathrow International Airport. An insight into Heathrow’s planning and preparation and its outstanding level of services and commitment will explain operation management practices being observed by the organisation. For example, winter resilience enquiry recently examined and implemented by operation management ensures its ability to provide excellent services and support given to passengers and employees during severe weather conditions, (Heathrow, 2011). The winter resilience initiative was carried out by operation management teams through expert peer review and extensive quality assurance. Teams studied and learned from Dallas Fort Worth, Madrid and Minneapolis-St. Paul airports which possess strong reputation for passenger welfare, airport operations and the clearance of snow. The devised plan for Heathrow was being examined and peer reviews helped it to carry out one of the most effective operation management tasks. For this, Heathrow had invested marvelously in acquiring innovative equipment which could effectively clear the airfield in reduced time. The equipment included taxiways, airside roads, runways, stands etc. and were used for the disposal of collected ice  and snow. This one task brought the Heathrow airport to fully operational status. It in fact appointed a full-time operations manager for winter that is responsible for Airport’s winter readiness controlled. The regular refinement and review of organisationâ €™s plans distinguishes it from other leading airports all over the world, (Heathrow, 2011). 2.2.Nestlà © UK Chocolate Factory Nestlà ©Ã¢â‚¬â„¢s brand and product portfolio ranges from local favorites to global icons. The products are supported by vigorous research and development facility, focused driving renovation and innovation, and with clear priorities which is attractive and relevant for consumers. Nestlà ©Ã¢â‚¬â„¢s desire in becoming a leader of renovation and innovation, whether of systems, processes or products define the role of governing operation management body which gives its product an entire new and refreshing aspect. From brand effectiveness to effective supply chain, from farm to the fork, nestle UK chocolate factory ensured best production and operation management. Best raw materials are being used in the preparation of chocolate and other products. For operations needs, nestle has set four pillars for effective operation management which include; increasing effectiveness and efficiency, operational efficiency, improved quality and elimination of waste. For continuous excellence and to make most innovative and appreciated products in most efficient way, nestle has implemented these four pillars into its operational management structure. The product and operational excellence has been given utmost importance all because Nestle ensures to provide its consumers with delightful products whenever and wherever they need them. Customer satisfaction is undoubtedly complimentary in consumer product market and Nestle has significantly earned it through continuous planning and operational excellence besides giving its products the desired and unmatched taste and nutrition, (Nestle, 2011). 3.Major Understandings of the study Major understandings of the study suggest that operation management is, by far, one of the most significant aspects of any organisation’s development and economic growth. It provides enormous value to the resources of the organisation and adds value to them. The resources and investments of any  organisation need to be utilized in more effective way for on-going progress. Furthermore, strategic planning division works hand-in-hand with operation management as it provides sustainable grounds for effective and efficacious planning and preparation. Indeed no organisation can survive without future plans and policies that define its objectives and goals and its overall competitive market value. Operation management thus promises sustainable future for the organisations and procures enormous economic growth under controlled conditions (Everett, E. Adam, Jr.Ronald J.Ebert, 1994). Another great aspect of operation management is its ability of giving added value to products and services of the organisation. It is aimed at increasing the efficiency of the products and services by minimizing the circumstances that may prevent organisations to achieve great market value for their products and services. As it is clear as crystal that today’s competitive environment demands higher level of excellence and efficiency from manufacturers and service providers, organisations should concentrate more and more on improving their standards. This can only be done through sustainable operation management plans and procedures. Furthermore, operation management not only serves as great tool in improving standards and adding value to goods and services, it has been proved as cost reduction tool within the framework of organisations. Great amount of capital and resources could be saved by implementing a resourceful and sustainable operation management plan which will ultimately turn the organisation into leading brand. To earn a competitive advantage in business sector, one needs to overlook every aspect that could affect it either positively or negatively. Only then unmatched products and excellent services can be manufactured and being provided (Hill, Terry, 1993). 4.Conclusions Operation management works in combination to several support and core functions of the organisation. It also increases the potential and performance of those areas where strategic and effective operation handling is essential. The scope of operation management is never dying and it embraces internal and external factors associated with business of any organisation. From manufacturing to supply, from marketing to customer satisfaction, from financing to human resource, operation management has its deep roots in the organisation’s framework (S. Anil Kumar, N. Suresh, 2008). Two case studies helped in understanding the role of operation management and how it can be utilized in improving overall performance of the organisations. Heathrow Airport is among world’s leading organisations that provide its customers with excellent services and it managed to sustain that position through years by effective operation management procedures. It has assigned one fourth of its employees to operational tasks which ensures greatest level of quality service. On the other hand, Nestlà ©Ã¢â‚¬â„¢ employed a tremendous operation management task force to maintain its brand value. It is evident of the fact why nestle consumers prefer its products over other brands. It has successfully achieved a competitive advantage over other foods and beverage companies operating all over the world through systemic and devoted operation management and planning. Concluding, the most significant role operation management plays is ensuring greater levels of customer satisfaction for the organisations for their brands, products and services. Customer satisfaction is utmost objective of any organisation and it will require that organisation to develop, implement and manage a sustainable operation management plan that could work in vicinity of other necessary activities and operations. Operation managers at organisations have the utmost responsibility in promising desired levels of satisfaction among consumers and customers thus fulfilling requirements for achieving basic objectives for the organisation. Their role in economic development is as essential as organisation’s survival in the competitive environment (Chambers et al, 2007) References †¢Chambers, Stuart, Johnston, Robert and Slack, Nigel (2007) Operations management (5th ed) †¢Dilworth, James B. (1999) Operations management : providing value in goods and services. (3rd ed) †¢Everett, E. Adam, Jr.Ronald J.Ebert, 1994. â€Å"Production and Operations Management†, Prentice-Hall of India Private Limited, 5th Edition †¢Heathrow, 2011. â€Å"Heathrow Winter Resilience Programme†, [online] Available at: [Accessed: 03rd December 2012] †¢Heizer, Jay H. and Render, Barry (2008) Operations management (9th ed) †¢Hill, Terry (1993) The essence of operations management †¢Joseph, G. Monks, 2004. â€Å"Theory and Problems of Operations Management†, Tata McGraw-Hill Publishing Company Limited, 2nd Edition †¢Joseph, G. Monks, â€Å"Operations Management†, McGraw-Hill International Edition, 3rd Edition. †¢Nestle, 2011, â€Å"Annual Report 2011†, [Online] Available at: [Accessed: 03rd December 2012] †¢R. Pannerselvam, 2004, â€Å"Production and Operations Management†, Prentice-Hall of India Private Limited, 9th print †¢S. Anil Kumar, N. Suresh, 2008, â€Å"Production and Operations Management, New Age International (P) Limited Publishers, 2nd Edition †¢Slack et al, Operations Management 4th Edition online version †¢Slack et al, Operations Management 6th edition online version †¢Waters, C. D. J. (1991) An introduction to operations management

Analysis of SAMe as an Antidepressant

Analysis of SAMe as an Antidepressant S-Adenosyl-Methionine (SAMe) And Improved Methylation Offer A Serious Alternative To Orthodox Medications Can S-Adenosyl-Methionine (SAMe) and improved methylation offer a serious alternative to orthodox medications in the treatment of depression? Abstract In this dissertation we consider the issues surrounding the use of SAMe as an antidepressant. There are many different aspects to this consideration. We start by a consideration of exactly what depression is on a clinical basis and examine the psychological and physiological changes that characterise the condition. We then consider and examine the evolution of the current forms of antidepressant medication. We explore the fields of neurochemistry and pathophysiology of depressive states with particular emphasis on the chemistry of the methylation reaction and its relevance to the SAMe compound. Consideration is then given to SAMe specifically as a medication and the evidence that there is to support its apparent beneficial effect in depression. This is then expanded with a review of the chemistry of SAMe and its interactions with other biologically active entities. We conclude the exploration with a critical review of the published literature that is relevant to the role of SAMe as an antidepressant agent. Introduction In order to investigate the full extent of the question at the heart of this dissertation we must examine a number of background issues in some detail first. Depression is a complex clinical state. It has been said that there are as many theories about the aetiology and treatments for depression as there are clinicians thinking about the problem. (LeDoux, J. 1996). A brief examination of the literature on the subject tells us that this comment, although clearly intended to be flippant, may not actually be so very far from the truth. Perhaps it is because of the plethora of hypotheses, ideas and theories on the issue that there are also a considerable number of forms of treatment that are commonly employed. It has to be admitted that some are rational and some appear to be completely irrational. In this dissertation we shall examine some of the more rational forms of psychopharmacology in order to understand the place of SAMe in the therapeutic pharmacopoeia. Depression is a commonly occurring illness. It will significantly affect between 10-25% of women and approximately half that number of men during their lifetimes. Approximately 5 million people in the UK will experience significant depression in any given year. (Breggin 1994) If you suffer from an acute or chronic illness you are even more likely to suffer from depressive states with frequencies ranging from 30-50% depending upon the nature and severity of the illness. (Robertson et al 1997) What is depression ? There are many definitions of clinical depression and indeed many different rating scales which purport to try to quantify it. It is important to distinguish between clinical depression and simply feeling down or miserable. Depressive illness typically occurs in episodes although in some cases it can actually last for many months or even years. (Skolnick, P. 1999). One severe depressive episode is a major independent risk factor for getting further episodes. In other words, having had depression once you are statistically considerably more likely to have another attack. (Post RM. 1992). For our purposes we shall consider a practical overview of the nine classic symptoms that characterise classical depression 1. Depressed mood for most of the day 2. Disturbed appetite or change in weight 3. Disturbed sleep 4. Psychomotor retardation or agitation 5. Loss of interest in previously pleasurable activities; inability to enjoy usual hobbies or activities 6. Fatigue or loss of energy 7. Feelings of worthlessness; excessive and/or inappropriate guilt 8. Difficulty in concentrating or thinking clearly 9. Morbid or suicidal thoughts or actions. (After Zuess 2003) The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) states that in order to merit a diagnosis of clinical depression you need to demonstrate at least five of these symptoms and that they represent a change in your life. Mood alterations are commonplace in depressive states. The depressed patient will classically feel despair or sadness. Pleasure becomes an alien emotion as they tend to progressively loose interest in activities that they would have previously enjoyed. Mood swings can also occur although they are more commonly found in bipolar states (manic depression). Subjective feelings of tension or irritability are often described as well as just sadness. (Duman et al 1997) In addition to mood changes, depression can also produce changes in the emotional state as well. Feelings of worthlessness and guilt are perhaps the commonest emotions in the clinical spectrum. This is closely followed by both ineptitude and lack of confidence in ones own abilities or capabilities. It is common for depressed people to take action that avoids them having to take responsibility because of an overwhelming fear of failure. (Altar CA 1999) Somatic manifestations of depression are perhaps easier to quantify as they have a qualitative characteristic about them as opposed to the purely subjective. Changes in appetite are commonly found. Generally it is an anorexic change with a decrease in appetite and a loss of interest in food generally. Less frequently, the converse is observed with a voracious increase in appetite (comfort eating) which is normally associated with weight gain. This weight gain can be quite substantial in extreme cases. Sleep disturbances are commonplace. Insomnia and early waking are perhaps the commonest of this type of symptom. This can occur despite severe subjective symptoms of somatic tiredness and fatigue. Some people will find that fatigue is a prominent symptom and may find that this is translated into excessive sleeping and motor retardation generally. Fatigue is actually more difficult to quantify, but it is commonly experienced by the depressed patient. It can either be an overwhelming tiredness (lack of energy) or perhaps lack of stamina (tiring too easily). Associated with this is often a reduction in libido and, if severe, impotence can also occur. It is not unusual to find sexual avoidance behaviours developing in these circumstances. (Janicak et al 1989) Concentration is commonly impaired. Generally speaking the greater the degree of depression, the greater is the degree of concentration impairment. Thinking and reasoning processes slow down and the attention span is often markedly reduced. Students find they can have an inability to study and if severe, patients report an inability to even sit and watch television. (Bazin et al 1994) Somatic symptoms can occur without the psychological elements of the depression being apparent or obvious. This is a common clinical dilemma. Patients may enter a phase of denial or minimisation where they will not accept that they are actually depressed. They can try to rationalise their physical symptomatology into other disease processes. This can be mistaken for hypochondriasis. (De Vanna et al 1992) If depression is severe (or occasionally part of a symptom complex of another underlying pathology), then psychosis can be found. Delusional states are not uncommon in severe depression. Hallucinations can occur, but they are comparatively unusual. Patients can state that they hear voices telling them that they are worthless or perhaps instructing them to kill themselves. Although this is consistent with a depressive diagnosis, one should note that other illnesses such as schizophrenia must clearly be considered and excluded before a confident diagnosis of depression can be made. The actual basis or specific triggering factors for depression are not yet clearly defined but we do know that a number of different biological factors are relevant. Environmental factors, together with both genetic and neurobiological elements are all capable of influencing the overall clinical picture. (Kendler KS, 1998). Depression is broadly divided into endogenous and reactive types. In general terms endogenous depression is thought to be influenced the genetic and neurobiological factors whereas reactive depression may well have environmental factors as being relevant. This has considerable implications in our considerations of the possible actions of SAMe. (Gold et al 1988) Pharmacology of depression This is a vast subject and is generally considered to be a sub-speciality in its own right. It has long been recognised that certain substances appear to be able to exert a mood elevating effect. The advent of modern psychopharmacology allowed us to develop an understanding into just how some of these substances work. The drugs and medicines that are in common use today are the result of a process of evolution that, arguably, began with the uses of herbs at the beginning of recorded history and progressed to the chemically and biologically sophisticated compounds that are in use today. (Peinell and Smith 2003) In order to put the SAMe compounds into their appropriate place in the continuum we need to look at some of the evolutionary developments in the field. Most of the currently used antidepressants work by interfering in some way with the actions of the various neurotransmitters in the brain. Many work by slowing down the biological processes of degradation or destruction of these neurotransmitters. In purely simplistic terms, this results in a greater concentration of the neurotransmitter at the critical synaptic interfaces within the brain. (Levine et al 1998) The first real breakthrough with what could be considered to be a major therapeutic agent for depressive states came with the discovery of the MAOI (Monoamine Oxidse Inhibitors), group of drugs. Three were commonly used in clinical practice isocarboxazid, phemelzine and tranlcypromine. For a while they were used extensively but it became obvious that they had serious drawbacks including some potentially fatal side effects. (Saarelainen et al 2003), Headaches dizziness and tremor were not unusual accompaniments of the drug. They also had the ability to interact with other medications and certain types of food (tyrosine containing foods such as cheese could cause hypertensive crises). Despite these drawbacks, many patients were willing to take them because they indisputably worked. (Skolnick 1999) In time, the MAOis were superseded by the Tricyclic group of drugs. There were four in common use, namely amitriptyline, desipramine, imipramine and nortriptyline. These were generally speaking, marginally more effective than the MAOIs but they were without the worst of the side effects. Despite that, they were still able to cause dry mouth and blurred vision in some people. Constipation and drowsiness were not unusual and they were not commonly used if a person also had hypertension. The pharmaceutical industry then produced a number of different categories of medication in fairly quick succession. SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin and norepinephrine reuptake inhibitors) and NDRIs (Norepinephrine and dopamine reuptake inhibitors) all emerged into the market place. (Smith et al 2004) It is probably fair to say that they all had their niches in the therapeutic spectrum but the SSRIs were seen to corner the biggest share of the clinical market with citalopram, escitalopram, fluoxetine, paroxetine and sertraline as examples of the group. Fluoxetine was probably the most widely used and its trade name, Prozac was accepted almost as a household word. The side effect profile of this particular group was certainly less significant than their predecessors, but nausea and headaches were not uncommon. (Stewart et al 2000), The SNRIs fell into disuse largely because of their reputation in raising cholesterol levels and the NDRIs were found to cause unacceptable agitation in certain groups. There was then an emergence of a group of drugs which not only blocked the mechanisms that removed the trophic neurotransmitters from the synapse they also had an effect which effectively enhanced their action by blocking the action of the inhibitory neurotransmitters at the same time. There are several types of medication in this category, but perhaps the best known is maprotilene. Like most of the other types of effective medication, it is not without side effects. Drowsiness, nausea, dizziness and a dry mouth are common accompanying symptoms of a therapeutic dose of this medication. (Harmer et al 2003) Neurochemistry and pathophysiology of depression So far we have take a brief and admittedly comparatively simplistic tour of the nature and pharmacology of depression. We shall now look at the neurochemistry and pathophysiology of certain relevant aspects of the subject in more detail. In general terms, stress and antidepressants appear to have reciprocal actions on neuronal growth and to some extent, on their activity (see on). This appears to be through the mediation of various neurotrophins and the action of synaptic plasticity mainly in the region of the hippocampus and some other brain structures (Reid et al 2001). Various stresses appear to disturb and disrupt the activity, both of individual neurones and also larger functional groups, or networks of neurones whereas antidepressants appear to antagonise this disruptive ability. (Henke 1990) There is a large body of opinion which agrees with the hypothesis that regulation of synaptic activity is a major key to the pathophysiology of depression and related disorders. (Drevets et al 1997) The discovery of the MAOI group of drugs (above) led researchers to speculate that the monoamine group of neurotransmitters were central to the aetiology of depression. As more research is done it is becoming apparent that this may not actually be the case. It is now considered more likely that the fundamental problems lie further along the metabolic cascade from the monoamine oxidase activity. It is also considered likely that the pathology may well not be just a chemical imbalance, but may well involve other functions of neural tissue such as various cellular changes in physiology, genetic factors and the ability of neuronal network to change their characteristics. (Czyrak et al 1992) Observational studies have suggested that early life experiences, the impact of stress and the presence or absence of social support or interactions all have an influence on the development of a depressive state. (Gould et al 1998).Consideration of the monoamine chemistry clearly does not account for all of these factors although it is clearly acknowledged that it does play an important contributory role. Some recent work relating to the chronic use of different classes of antidepressants (Duman et al 1997), has appeared to show that they all are able to increase the production of the neuroprotective groups of proteins which, amongst other actions, play a central role in the plasticity of neurones. Current thinking is that this may well be a common function of a number of different pathways that the different antidepressants exploit. It is known that increases in monoamine levels in the synaptic region result (by a number of different mechanisms) and are associated with the induction of enzyme systems that control gene expression within the neurone. This can be inferred from the finding of increases in the levels of messenger RNA which codes for the cAMP response element binding protein (CREB). These levels slowly increase with chronicity of administration of antidepressants and this mechanism may well account therefore for the commonly observed slow and progressive onset of action of most of the antidepressant drugs. It is proposed that CREB triggers the production of BDNF (Brain Derived Neurotrophic Factor). This is significant since other work has shown that stress antagonises the levels of BDNF which is opposed by the actions of the antidepressant drugs. (Smith et al 1995). Further credence is given to this theory with the discovery that placing BDNF directly into the brain of experimental animals appeared to relieve many of the behaviour patterns that are associated with depression (Siuciak et al 1997) Some authors have suggested that depression may represent a particularly subtle form of neural degenerative disorder as it has been shown that the hippocampus becomes progressively atrophic in chronic depressive states. This is particularly significant as BDNF is thought to reverse such findings. (Shah et al 1998). There is associated supporting evidence in the form of a study by Vaidya (et al 1999) which shows that ECT treatment (which was always assumed to be detrimental to the neural structure and physiology) is associated with both increased levels of BDNF and trophic changes in the hippocampal neurones. A paper by Czyrak (et al 1992) looked at the antidepressant activity of SAMe in mice and rats in a way that clearly is not possible in humans. It is not always possible to directly extrapolate findings from animals to humans, but there are some pieces of evidence in this work which strongly implicate SAMe in the pathogenesis of depression. The paper itself is extremely long and complex but the relevant parts to our considerations here are the fact that normal geographical exploratory behaviour in rodents tends to diminish if a depressive state is induced. To some extent, exploratory behaviour is therefore considered a marker for the depressive state. It was found that SAMe tended to increase exploratory activity in mice. This, and other more sophisticated testing of the pharmacological interactions of SAMe showed that it tended to have the same psychopharmacological profile as many of the mainstream antidepressants. Many of the neurotransmitters and for that matter some neuroactive hormones have been variously implicated in the aetiology of depression (eg thyroid hormones and noradrenaline). (Nemeroff, 1998). Modern research has most consistently found that alterations in the levels of serotonin (5-HT) (Melzter H, 1989), system and the chemicals of the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. (Kathol et al 1989), as the most consistently implicated mechanisms that appear to be associated with the control of the mood stabilising and regulating mechanisms. It is in fact very likely that both these mechanisms are in some way interlinked as part of the regulatory mechanism of mood. We have already referred to the role of stress in the aetiology of depression. We know that the adrenal glucocorticoid hormones subtly interact with the 5-HT system and these are produced in direct response to stress. (Lopez et al 1999) (I). We also know that the glucocorticoids have a number of direct effects on the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. It may be that this is the mechanism by which stress antagonises the changes brought about by SAMe. (Lopez et al 1999) (II) We do not need to consider the effects of the corticoids on the LHPA axis in detail as it is only of peripheral relevance to our considerations here. The important consideration in this regard is that the LHPA axis is intimately connected to the hippocampus. It is this structure that is the intermediate step and connection between the bodys hormonal response to stress and the response of the higher functions of the brain. (Dallman et al 1987). The immediate relevance of all this to the actions of SAMe are that hyperactivity of both the hippocampus and the LHPA axis are both well documented in cases of clinical depression. This has been shown to also be associated with high levels of corticosteroid production (Kalin et al 1987), but one study has shown that in suicide cases who have had profound depression the hippocampus has fewer corticosteroid receptor sites than one might normally expect (Lopez et al 1998). One further piece of clinical evidence in the role of the corticosteroids in depression is that patients with Cushings disease have a high incidence of depression. This incidence returns to normal when their hormonal over-activity is treated and returned back to physiological levels. (Murphy 1991) SAMe as a medication SAMe was discovered in Italy in 1952 during research into the chemistry of neurotransmitters. It was not, however, introduced in a useable form for patient benefit until 1974 (as SAMe sulphate-paratoluene-sulphonate). It is for this reason that the majority of the early papers and work on the subject are almost exclusively Italian in origin. (De Vanna et al 1992) SAMe has been used clinically in a number of conditions including cholestasis, osteoarthritis and depression. (Carney et al 1987) Although there is a wealth of literature on the first two elements it is not relevant to our considerations here. We shall therefore restrict this discussion to the spectrum of its use in the field of depression. A number of studies have shown that SAMe has useful activity in depressive illness. Studies that have compared it to placebo have found that it can consistently produce about a 6 point increase on the Hamilton rating scale after about three weeks of optimum treatment. This finding is approximately in line with the results that are found with most of the other clinically effective antidepressant medications. (Cooper et al 1999) (De Vanna et al 1992) Some studies have found that using SAMe in a large dose has produced an unusually rapid onset of beneficial effects (Kagan 1990) One could argue that, because it is a naturally occurring substance, it would not be likely to have a high side-effect profile. Although these two statements do not always follow, it is generally true. A study by Bressa (1994) on the issue showed that it did have a particularly low side-effect profile, particularly when compared to the other antidepressants (Tricyclics). To demonstrate this point further, we can point to the study by Caruso (et al 1987) where there were a greater number of patient withdrawals due to the side effects of the placebo than withdrew because of the SAMe drug. For the record, that particular trial was in its use as an antiarthritic rather than an antidepressant, but the point is made. The two major unwanted clinical effects are nausea and hypomania. The nausea is not a local effect on the gut lining but appears to be a centrally mediated effect and is possibly caused by the same phenomenon of over-stimulation of the neuronal networks which causes the other major clinical manifestation of hypomania. For this reason it is generally not used in cases of bipolar disorder. (De Vanna et al 1992) It is probably not strictly accurate to refer to SAMe as a drug as it is normally found in the cellular matrix. It has been found to be effective in patients who have been unable to tolerate other forms of antidepressants or, for that matter, have had minimal response to them. (Reynolds et al, 1984) Young (1993) produced a particularly interesting review of dietary treatments for depression. A lot of his article is not relevant to our considerations here, but he makes a number of interesting and relevant observations. Low serotonin levels are known to be associated with depression even though low levels on their own do not appear to cause the condition. It appears that it needs to be in combination with a low level of folic acid. We know that low levels of folic acid are also often found in combination with depressive illness and that low levels of folate are often associated with low levels of SAMe. The evidence points to the fact that the low levels of serotonin are more likely to be a result of the low SAMe levels in neural tissue and that this is more likely to be nearer to the root of the main anomaly that causes depression. Pregnancy is known to be associated with low levels of folate and post natal depression is a well recognised clinical entity. Salmaggi (et al 1993) considered the effects of SAMe in the postnatal period. This was a well considered and constructed study. It was a double blind placebo controlled trial over a 30 day period and had an entry cohort of 80 women. The degree of depression was assessed before, during and after the trial on the Hamilton Scale. The results showed a statistically significant improvement in the SAMe group when compared to the placebo group. The authors comment that there were no significant side effects of the medication encountered. Because we know that any beneficial effect that SAMe is likely to have on a patient tends to be seen more quickly than with the other antidepressants, and also, by virtue of what we suspect about its probable mode of action in the hippocampus and elsewhere in the brain, it seems a logical step for someone to look into the effects of giving SAMe alongside a conventional antidepressants to see if there is either any synergistic effect or possibly a speeding up of the clinical onset of the secondary medication. The study by Berlanga (et al 1992) did exactly that. Unfortunately the trial was not particularly rigorous in its design as although it was double blind, it was not placebo controlled, which would appear to have been the method of choice in this type of investigation. Its other problem as that it only had an entry cohort of 40 patients. Despite these limitations it was indeed shown that depressed patients who took SAMe in conjunction with other antidepressant medication found that the depressive symptoms resolved faster with the SAMe added to their normal treatment regime. There are one or two other less important papers which we shall only mention in passing. Kagan (et al 1990) ran a small trial on 15 inpatients (with very severe depression) and found SAMe to be a safe, effective antidepressant with few side effects and a rapid onset of action. This particular trial is notable as it was the first to report the side effect of mania in a patient who didnt have a previous history. Another is the trial by Rosenbaum (et al 1990). This particular trial is notable for the demonstration of the fact that about 20% of other treatment resistant patients experienced benefit with SAMe. Faya (et al 1990) (II) considered the fact that SAMe is thought to exert its effect through its action in increasing dopamine levels in the synaptic cleft. It is known that dopamine inhibits the production of both Thyroid stimulating hormone (TSH) and Prolactin from the pituitary gland. Faya considered measuring the levels of both TSH and Prolactin during treatment with SAMe. His findings constituted something of a surprise insofar as in the men in the trial group had their levels of TSH and Prolactin reduced which is consistent with the hypothesis that SAMe increases the dopamine levels in the brain. Much to everybodys surprise, this effect was not seen in the female group. The authors do not offer any explanation of this fact. For the record, there is another trial (Thomas et al 1987), which obviously considered the same phenomenon and their trial did not show any sex linked difference in the suppression of the Prolactin levels With regards to efficacy, a trial by Carney (et al 1986) suggests that the beneficial action of SAMe is restricted to endogenous depression and it does not appear to have any action above placebo on reactive depression. As far as we can ascertain, this is the only trial published that has made this suggestion, although from a first principles basis, one can see the biochemical rationale for believing that it might well be the case. On a purely empirical grounds, some authors have recommended (on the basis of scant hard evidence), that SAMes action can be maximised by the addition of B12, B6 and folic acid. It is known that SAMe is required to convert these agents into their active form as a coenzyme. (Morrison et al, 1996). The same author also recommends the simultaneous adminstration of Trimethylglycine (TMG) which is necessary for the intracellular conversion of methionine into SAMe by the provision of the necessary methyl- groups. Comment has to be made that again, this appears to be a completely empirical (and logical) suggestion, but we cannot find any hard evidence to substantiate its clinical use. Chemistry SAMe is a basic component of cellular biochemistry. It occurs in every living cell and is second in importance only to ATP in both the number variety and significance of the reactions in which it serves as a cofactor. (Stramentinoli 1987). It is central in the chemistry of the transmethylation reactions. In essence its cellular function is to transfer the active methyl group form carrier molecules to a multitude of other molecules. In general terms, this methylation makes inert molecules biologically active. In addition to the transmethylation reactions it also plays a central role in transsulfuration and aminopropylation reactions It is involved in the synthesis of proteins including the nucleic acids, fatty acids, lipids and phospholipids, porphyrins and polysaccharides. In terms of our considerations here, perhaps the most significant reaction type that SAMe is involved in is the generation of the neurotransmitter amines. In this regard it is considered to be the most biologically significant provider of methyl groups within the cell. (Baldessarini 1987). Significantly it is also involved in the pathways to produce a number of other neurologically active compounds such as adrenaline, the neuronutrients acetyl l-carnitine and phosphatidyl choline (Mathews et al 1990) It is also to be found in the metabolic pathways of both serotonin and dopamine. Oral administration has been shown to increase the metabolites of these compounds in the CSF (implying increased turnover). It is thought to exert its antidepressive effect partly through the mechanism of increasing the levels of both dopamine and serotonin as neurotransmitters, but it also appears to have some form of trophic action on some of the neurones in the brain cortex. (Baldessarini 1987) It has been demonstrated that the tissue levels of SAMe tend to diminish with age and blood levels are also found to be low in some cases of clinical depression (Baldessarini 1987) A methyl group (CH3) is a group of three hydrogen atoms bound to one carbon atom. It does not exist in a stable isolated form and is transported between molecules by intermediaries such as SAMe. Methylation is the process by which this group is transferred from the methyl donor molecule to the recipient molecule. In general terms this process is central to the control of many of the intracellular pathways. Giving a methyl group to an enzyme is often the key to activating it, and thereby beginning a synthesis or degradation process elsewhere in the cell. Equally removing the methyl group will render the enzyme inactive and stop that particular pathway. Similar mechanisms are involved in the expression of genes and therefore the production of proteins within the cell. Some specific methylation reactions include the methylation of phenols which detoxify them and thereby aid in their excretion. (Stramentinoli 1987) In the context of this dissertation, methylation is also central to the metabolic chemistry of serotonin (and therefore also melatonin). The activity of both these compounds is effectively regulated by the presence of a methyl group. SAMe is synthesised from methionine, a naturally occurring amino acid. As the name implies (METH-ionine), it contains a methyl group. By utilising the energy supplied by ATP and in the presence of magnesium, it is converted into SAMe. The process is catalysed by the intervention of the enzyme MAT (methionine adenosyl Analysis of SAMe as an Antidepressant Analysis of SAMe as an Antidepressant S-Adenosyl-Methionine (SAMe) And Improved Methylation Offer A Serious Alternative To Orthodox Medications Can S-Adenosyl-Methionine (SAMe) and improved methylation offer a serious alternative to orthodox medications in the treatment of depression? Abstract In this dissertation we consider the issues surrounding the use of SAMe as an antidepressant. There are many different aspects to this consideration. We start by a consideration of exactly what depression is on a clinical basis and examine the psychological and physiological changes that characterise the condition. We then consider and examine the evolution of the current forms of antidepressant medication. We explore the fields of neurochemistry and pathophysiology of depressive states with particular emphasis on the chemistry of the methylation reaction and its relevance to the SAMe compound. Consideration is then given to SAMe specifically as a medication and the evidence that there is to support its apparent beneficial effect in depression. This is then expanded with a review of the chemistry of SAMe and its interactions with other biologically active entities. We conclude the exploration with a critical review of the published literature that is relevant to the role of SAMe as an antidepressant agent. Introduction In order to investigate the full extent of the question at the heart of this dissertation we must examine a number of background issues in some detail first. Depression is a complex clinical state. It has been said that there are as many theories about the aetiology and treatments for depression as there are clinicians thinking about the problem. (LeDoux, J. 1996). A brief examination of the literature on the subject tells us that this comment, although clearly intended to be flippant, may not actually be so very far from the truth. Perhaps it is because of the plethora of hypotheses, ideas and theories on the issue that there are also a considerable number of forms of treatment that are commonly employed. It has to be admitted that some are rational and some appear to be completely irrational. In this dissertation we shall examine some of the more rational forms of psychopharmacology in order to understand the place of SAMe in the therapeutic pharmacopoeia. Depression is a commonly occurring illness. It will significantly affect between 10-25% of women and approximately half that number of men during their lifetimes. Approximately 5 million people in the UK will experience significant depression in any given year. (Breggin 1994) If you suffer from an acute or chronic illness you are even more likely to suffer from depressive states with frequencies ranging from 30-50% depending upon the nature and severity of the illness. (Robertson et al 1997) What is depression ? There are many definitions of clinical depression and indeed many different rating scales which purport to try to quantify it. It is important to distinguish between clinical depression and simply feeling down or miserable. Depressive illness typically occurs in episodes although in some cases it can actually last for many months or even years. (Skolnick, P. 1999). One severe depressive episode is a major independent risk factor for getting further episodes. In other words, having had depression once you are statistically considerably more likely to have another attack. (Post RM. 1992). For our purposes we shall consider a practical overview of the nine classic symptoms that characterise classical depression 1. Depressed mood for most of the day 2. Disturbed appetite or change in weight 3. Disturbed sleep 4. Psychomotor retardation or agitation 5. Loss of interest in previously pleasurable activities; inability to enjoy usual hobbies or activities 6. Fatigue or loss of energy 7. Feelings of worthlessness; excessive and/or inappropriate guilt 8. Difficulty in concentrating or thinking clearly 9. Morbid or suicidal thoughts or actions. (After Zuess 2003) The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) states that in order to merit a diagnosis of clinical depression you need to demonstrate at least five of these symptoms and that they represent a change in your life. Mood alterations are commonplace in depressive states. The depressed patient will classically feel despair or sadness. Pleasure becomes an alien emotion as they tend to progressively loose interest in activities that they would have previously enjoyed. Mood swings can also occur although they are more commonly found in bipolar states (manic depression). Subjective feelings of tension or irritability are often described as well as just sadness. (Duman et al 1997) In addition to mood changes, depression can also produce changes in the emotional state as well. Feelings of worthlessness and guilt are perhaps the commonest emotions in the clinical spectrum. This is closely followed by both ineptitude and lack of confidence in ones own abilities or capabilities. It is common for depressed people to take action that avoids them having to take responsibility because of an overwhelming fear of failure. (Altar CA 1999) Somatic manifestations of depression are perhaps easier to quantify as they have a qualitative characteristic about them as opposed to the purely subjective. Changes in appetite are commonly found. Generally it is an anorexic change with a decrease in appetite and a loss of interest in food generally. Less frequently, the converse is observed with a voracious increase in appetite (comfort eating) which is normally associated with weight gain. This weight gain can be quite substantial in extreme cases. Sleep disturbances are commonplace. Insomnia and early waking are perhaps the commonest of this type of symptom. This can occur despite severe subjective symptoms of somatic tiredness and fatigue. Some people will find that fatigue is a prominent symptom and may find that this is translated into excessive sleeping and motor retardation generally. Fatigue is actually more difficult to quantify, but it is commonly experienced by the depressed patient. It can either be an overwhelming tiredness (lack of energy) or perhaps lack of stamina (tiring too easily). Associated with this is often a reduction in libido and, if severe, impotence can also occur. It is not unusual to find sexual avoidance behaviours developing in these circumstances. (Janicak et al 1989) Concentration is commonly impaired. Generally speaking the greater the degree of depression, the greater is the degree of concentration impairment. Thinking and reasoning processes slow down and the attention span is often markedly reduced. Students find they can have an inability to study and if severe, patients report an inability to even sit and watch television. (Bazin et al 1994) Somatic symptoms can occur without the psychological elements of the depression being apparent or obvious. This is a common clinical dilemma. Patients may enter a phase of denial or minimisation where they will not accept that they are actually depressed. They can try to rationalise their physical symptomatology into other disease processes. This can be mistaken for hypochondriasis. (De Vanna et al 1992) If depression is severe (or occasionally part of a symptom complex of another underlying pathology), then psychosis can be found. Delusional states are not uncommon in severe depression. Hallucinations can occur, but they are comparatively unusual. Patients can state that they hear voices telling them that they are worthless or perhaps instructing them to kill themselves. Although this is consistent with a depressive diagnosis, one should note that other illnesses such as schizophrenia must clearly be considered and excluded before a confident diagnosis of depression can be made. The actual basis or specific triggering factors for depression are not yet clearly defined but we do know that a number of different biological factors are relevant. Environmental factors, together with both genetic and neurobiological elements are all capable of influencing the overall clinical picture. (Kendler KS, 1998). Depression is broadly divided into endogenous and reactive types. In general terms endogenous depression is thought to be influenced the genetic and neurobiological factors whereas reactive depression may well have environmental factors as being relevant. This has considerable implications in our considerations of the possible actions of SAMe. (Gold et al 1988) Pharmacology of depression This is a vast subject and is generally considered to be a sub-speciality in its own right. It has long been recognised that certain substances appear to be able to exert a mood elevating effect. The advent of modern psychopharmacology allowed us to develop an understanding into just how some of these substances work. The drugs and medicines that are in common use today are the result of a process of evolution that, arguably, began with the uses of herbs at the beginning of recorded history and progressed to the chemically and biologically sophisticated compounds that are in use today. (Peinell and Smith 2003) In order to put the SAMe compounds into their appropriate place in the continuum we need to look at some of the evolutionary developments in the field. Most of the currently used antidepressants work by interfering in some way with the actions of the various neurotransmitters in the brain. Many work by slowing down the biological processes of degradation or destruction of these neurotransmitters. In purely simplistic terms, this results in a greater concentration of the neurotransmitter at the critical synaptic interfaces within the brain. (Levine et al 1998) The first real breakthrough with what could be considered to be a major therapeutic agent for depressive states came with the discovery of the MAOI (Monoamine Oxidse Inhibitors), group of drugs. Three were commonly used in clinical practice isocarboxazid, phemelzine and tranlcypromine. For a while they were used extensively but it became obvious that they had serious drawbacks including some potentially fatal side effects. (Saarelainen et al 2003), Headaches dizziness and tremor were not unusual accompaniments of the drug. They also had the ability to interact with other medications and certain types of food (tyrosine containing foods such as cheese could cause hypertensive crises). Despite these drawbacks, many patients were willing to take them because they indisputably worked. (Skolnick 1999) In time, the MAOis were superseded by the Tricyclic group of drugs. There were four in common use, namely amitriptyline, desipramine, imipramine and nortriptyline. These were generally speaking, marginally more effective than the MAOIs but they were without the worst of the side effects. Despite that, they were still able to cause dry mouth and blurred vision in some people. Constipation and drowsiness were not unusual and they were not commonly used if a person also had hypertension. The pharmaceutical industry then produced a number of different categories of medication in fairly quick succession. SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin and norepinephrine reuptake inhibitors) and NDRIs (Norepinephrine and dopamine reuptake inhibitors) all emerged into the market place. (Smith et al 2004) It is probably fair to say that they all had their niches in the therapeutic spectrum but the SSRIs were seen to corner the biggest share of the clinical market with citalopram, escitalopram, fluoxetine, paroxetine and sertraline as examples of the group. Fluoxetine was probably the most widely used and its trade name, Prozac was accepted almost as a household word. The side effect profile of this particular group was certainly less significant than their predecessors, but nausea and headaches were not uncommon. (Stewart et al 2000), The SNRIs fell into disuse largely because of their reputation in raising cholesterol levels and the NDRIs were found to cause unacceptable agitation in certain groups. There was then an emergence of a group of drugs which not only blocked the mechanisms that removed the trophic neurotransmitters from the synapse they also had an effect which effectively enhanced their action by blocking the action of the inhibitory neurotransmitters at the same time. There are several types of medication in this category, but perhaps the best known is maprotilene. Like most of the other types of effective medication, it is not without side effects. Drowsiness, nausea, dizziness and a dry mouth are common accompanying symptoms of a therapeutic dose of this medication. (Harmer et al 2003) Neurochemistry and pathophysiology of depression So far we have take a brief and admittedly comparatively simplistic tour of the nature and pharmacology of depression. We shall now look at the neurochemistry and pathophysiology of certain relevant aspects of the subject in more detail. In general terms, stress and antidepressants appear to have reciprocal actions on neuronal growth and to some extent, on their activity (see on). This appears to be through the mediation of various neurotrophins and the action of synaptic plasticity mainly in the region of the hippocampus and some other brain structures (Reid et al 2001). Various stresses appear to disturb and disrupt the activity, both of individual neurones and also larger functional groups, or networks of neurones whereas antidepressants appear to antagonise this disruptive ability. (Henke 1990) There is a large body of opinion which agrees with the hypothesis that regulation of synaptic activity is a major key to the pathophysiology of depression and related disorders. (Drevets et al 1997) The discovery of the MAOI group of drugs (above) led researchers to speculate that the monoamine group of neurotransmitters were central to the aetiology of depression. As more research is done it is becoming apparent that this may not actually be the case. It is now considered more likely that the fundamental problems lie further along the metabolic cascade from the monoamine oxidase activity. It is also considered likely that the pathology may well not be just a chemical imbalance, but may well involve other functions of neural tissue such as various cellular changes in physiology, genetic factors and the ability of neuronal network to change their characteristics. (Czyrak et al 1992) Observational studies have suggested that early life experiences, the impact of stress and the presence or absence of social support or interactions all have an influence on the development of a depressive state. (Gould et al 1998).Consideration of the monoamine chemistry clearly does not account for all of these factors although it is clearly acknowledged that it does play an important contributory role. Some recent work relating to the chronic use of different classes of antidepressants (Duman et al 1997), has appeared to show that they all are able to increase the production of the neuroprotective groups of proteins which, amongst other actions, play a central role in the plasticity of neurones. Current thinking is that this may well be a common function of a number of different pathways that the different antidepressants exploit. It is known that increases in monoamine levels in the synaptic region result (by a number of different mechanisms) and are associated with the induction of enzyme systems that control gene expression within the neurone. This can be inferred from the finding of increases in the levels of messenger RNA which codes for the cAMP response element binding protein (CREB). These levels slowly increase with chronicity of administration of antidepressants and this mechanism may well account therefore for the commonly observed slow and progressive onset of action of most of the antidepressant drugs. It is proposed that CREB triggers the production of BDNF (Brain Derived Neurotrophic Factor). This is significant since other work has shown that stress antagonises the levels of BDNF which is opposed by the actions of the antidepressant drugs. (Smith et al 1995). Further credence is given to this theory with the discovery that placing BDNF directly into the brain of experimental animals appeared to relieve many of the behaviour patterns that are associated with depression (Siuciak et al 1997) Some authors have suggested that depression may represent a particularly subtle form of neural degenerative disorder as it has been shown that the hippocampus becomes progressively atrophic in chronic depressive states. This is particularly significant as BDNF is thought to reverse such findings. (Shah et al 1998). There is associated supporting evidence in the form of a study by Vaidya (et al 1999) which shows that ECT treatment (which was always assumed to be detrimental to the neural structure and physiology) is associated with both increased levels of BDNF and trophic changes in the hippocampal neurones. A paper by Czyrak (et al 1992) looked at the antidepressant activity of SAMe in mice and rats in a way that clearly is not possible in humans. It is not always possible to directly extrapolate findings from animals to humans, but there are some pieces of evidence in this work which strongly implicate SAMe in the pathogenesis of depression. The paper itself is extremely long and complex but the relevant parts to our considerations here are the fact that normal geographical exploratory behaviour in rodents tends to diminish if a depressive state is induced. To some extent, exploratory behaviour is therefore considered a marker for the depressive state. It was found that SAMe tended to increase exploratory activity in mice. This, and other more sophisticated testing of the pharmacological interactions of SAMe showed that it tended to have the same psychopharmacological profile as many of the mainstream antidepressants. Many of the neurotransmitters and for that matter some neuroactive hormones have been variously implicated in the aetiology of depression (eg thyroid hormones and noradrenaline). (Nemeroff, 1998). Modern research has most consistently found that alterations in the levels of serotonin (5-HT) (Melzter H, 1989), system and the chemicals of the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. (Kathol et al 1989), as the most consistently implicated mechanisms that appear to be associated with the control of the mood stabilising and regulating mechanisms. It is in fact very likely that both these mechanisms are in some way interlinked as part of the regulatory mechanism of mood. We have already referred to the role of stress in the aetiology of depression. We know that the adrenal glucocorticoid hormones subtly interact with the 5-HT system and these are produced in direct response to stress. (Lopez et al 1999) (I). We also know that the glucocorticoids have a number of direct effects on the Limbic Hypothalamic-Pituitary-Adrenal (LHPA) axis. It may be that this is the mechanism by which stress antagonises the changes brought about by SAMe. (Lopez et al 1999) (II) We do not need to consider the effects of the corticoids on the LHPA axis in detail as it is only of peripheral relevance to our considerations here. The important consideration in this regard is that the LHPA axis is intimately connected to the hippocampus. It is this structure that is the intermediate step and connection between the bodys hormonal response to stress and the response of the higher functions of the brain. (Dallman et al 1987). The immediate relevance of all this to the actions of SAMe are that hyperactivity of both the hippocampus and the LHPA axis are both well documented in cases of clinical depression. This has been shown to also be associated with high levels of corticosteroid production (Kalin et al 1987), but one study has shown that in suicide cases who have had profound depression the hippocampus has fewer corticosteroid receptor sites than one might normally expect (Lopez et al 1998). One further piece of clinical evidence in the role of the corticosteroids in depression is that patients with Cushings disease have a high incidence of depression. This incidence returns to normal when their hormonal over-activity is treated and returned back to physiological levels. (Murphy 1991) SAMe as a medication SAMe was discovered in Italy in 1952 during research into the chemistry of neurotransmitters. It was not, however, introduced in a useable form for patient benefit until 1974 (as SAMe sulphate-paratoluene-sulphonate). It is for this reason that the majority of the early papers and work on the subject are almost exclusively Italian in origin. (De Vanna et al 1992) SAMe has been used clinically in a number of conditions including cholestasis, osteoarthritis and depression. (Carney et al 1987) Although there is a wealth of literature on the first two elements it is not relevant to our considerations here. We shall therefore restrict this discussion to the spectrum of its use in the field of depression. A number of studies have shown that SAMe has useful activity in depressive illness. Studies that have compared it to placebo have found that it can consistently produce about a 6 point increase on the Hamilton rating scale after about three weeks of optimum treatment. This finding is approximately in line with the results that are found with most of the other clinically effective antidepressant medications. (Cooper et al 1999) (De Vanna et al 1992) Some studies have found that using SAMe in a large dose has produced an unusually rapid onset of beneficial effects (Kagan 1990) One could argue that, because it is a naturally occurring substance, it would not be likely to have a high side-effect profile. Although these two statements do not always follow, it is generally true. A study by Bressa (1994) on the issue showed that it did have a particularly low side-effect profile, particularly when compared to the other antidepressants (Tricyclics). To demonstrate this point further, we can point to the study by Caruso (et al 1987) where there were a greater number of patient withdrawals due to the side effects of the placebo than withdrew because of the SAMe drug. For the record, that particular trial was in its use as an antiarthritic rather than an antidepressant, but the point is made. The two major unwanted clinical effects are nausea and hypomania. The nausea is not a local effect on the gut lining but appears to be a centrally mediated effect and is possibly caused by the same phenomenon of over-stimulation of the neuronal networks which causes the other major clinical manifestation of hypomania. For this reason it is generally not used in cases of bipolar disorder. (De Vanna et al 1992) It is probably not strictly accurate to refer to SAMe as a drug as it is normally found in the cellular matrix. It has been found to be effective in patients who have been unable to tolerate other forms of antidepressants or, for that matter, have had minimal response to them. (Reynolds et al, 1984) Young (1993) produced a particularly interesting review of dietary treatments for depression. A lot of his article is not relevant to our considerations here, but he makes a number of interesting and relevant observations. Low serotonin levels are known to be associated with depression even though low levels on their own do not appear to cause the condition. It appears that it needs to be in combination with a low level of folic acid. We know that low levels of folic acid are also often found in combination with depressive illness and that low levels of folate are often associated with low levels of SAMe. The evidence points to the fact that the low levels of serotonin are more likely to be a result of the low SAMe levels in neural tissue and that this is more likely to be nearer to the root of the main anomaly that causes depression. Pregnancy is known to be associated with low levels of folate and post natal depression is a well recognised clinical entity. Salmaggi (et al 1993) considered the effects of SAMe in the postnatal period. This was a well considered and constructed study. It was a double blind placebo controlled trial over a 30 day period and had an entry cohort of 80 women. The degree of depression was assessed before, during and after the trial on the Hamilton Scale. The results showed a statistically significant improvement in the SAMe group when compared to the placebo group. The authors comment that there were no significant side effects of the medication encountered. Because we know that any beneficial effect that SAMe is likely to have on a patient tends to be seen more quickly than with the other antidepressants, and also, by virtue of what we suspect about its probable mode of action in the hippocampus and elsewhere in the brain, it seems a logical step for someone to look into the effects of giving SAMe alongside a conventional antidepressants to see if there is either any synergistic effect or possibly a speeding up of the clinical onset of the secondary medication. The study by Berlanga (et al 1992) did exactly that. Unfortunately the trial was not particularly rigorous in its design as although it was double blind, it was not placebo controlled, which would appear to have been the method of choice in this type of investigation. Its other problem as that it only had an entry cohort of 40 patients. Despite these limitations it was indeed shown that depressed patients who took SAMe in conjunction with other antidepressant medication found that the depressive symptoms resolved faster with the SAMe added to their normal treatment regime. There are one or two other less important papers which we shall only mention in passing. Kagan (et al 1990) ran a small trial on 15 inpatients (with very severe depression) and found SAMe to be a safe, effective antidepressant with few side effects and a rapid onset of action. This particular trial is notable as it was the first to report the side effect of mania in a patient who didnt have a previous history. Another is the trial by Rosenbaum (et al 1990). This particular trial is notable for the demonstration of the fact that about 20% of other treatment resistant patients experienced benefit with SAMe. Faya (et al 1990) (II) considered the fact that SAMe is thought to exert its effect through its action in increasing dopamine levels in the synaptic cleft. It is known that dopamine inhibits the production of both Thyroid stimulating hormone (TSH) and Prolactin from the pituitary gland. Faya considered measuring the levels of both TSH and Prolactin during treatment with SAMe. His findings constituted something of a surprise insofar as in the men in the trial group had their levels of TSH and Prolactin reduced which is consistent with the hypothesis that SAMe increases the dopamine levels in the brain. Much to everybodys surprise, this effect was not seen in the female group. The authors do not offer any explanation of this fact. For the record, there is another trial (Thomas et al 1987), which obviously considered the same phenomenon and their trial did not show any sex linked difference in the suppression of the Prolactin levels With regards to efficacy, a trial by Carney (et al 1986) suggests that the beneficial action of SAMe is restricted to endogenous depression and it does not appear to have any action above placebo on reactive depression. As far as we can ascertain, this is the only trial published that has made this suggestion, although from a first principles basis, one can see the biochemical rationale for believing that it might well be the case. On a purely empirical grounds, some authors have recommended (on the basis of scant hard evidence), that SAMes action can be maximised by the addition of B12, B6 and folic acid. It is known that SAMe is required to convert these agents into their active form as a coenzyme. (Morrison et al, 1996). The same author also recommends the simultaneous adminstration of Trimethylglycine (TMG) which is necessary for the intracellular conversion of methionine into SAMe by the provision of the necessary methyl- groups. Comment has to be made that again, this appears to be a completely empirical (and logical) suggestion, but we cannot find any hard evidence to substantiate its clinical use. Chemistry SAMe is a basic component of cellular biochemistry. It occurs in every living cell and is second in importance only to ATP in both the number variety and significance of the reactions in which it serves as a cofactor. (Stramentinoli 1987). It is central in the chemistry of the transmethylation reactions. In essence its cellular function is to transfer the active methyl group form carrier molecules to a multitude of other molecules. In general terms, this methylation makes inert molecules biologically active. In addition to the transmethylation reactions it also plays a central role in transsulfuration and aminopropylation reactions It is involved in the synthesis of proteins including the nucleic acids, fatty acids, lipids and phospholipids, porphyrins and polysaccharides. In terms of our considerations here, perhaps the most significant reaction type that SAMe is involved in is the generation of the neurotransmitter amines. In this regard it is considered to be the most biologically significant provider of methyl groups within the cell. (Baldessarini 1987). Significantly it is also involved in the pathways to produce a number of other neurologically active compounds such as adrenaline, the neuronutrients acetyl l-carnitine and phosphatidyl choline (Mathews et al 1990) It is also to be found in the metabolic pathways of both serotonin and dopamine. Oral administration has been shown to increase the metabolites of these compounds in the CSF (implying increased turnover). It is thought to exert its antidepressive effect partly through the mechanism of increasing the levels of both dopamine and serotonin as neurotransmitters, but it also appears to have some form of trophic action on some of the neurones in the brain cortex. (Baldessarini 1987) It has been demonstrated that the tissue levels of SAMe tend to diminish with age and blood levels are also found to be low in some cases of clinical depression (Baldessarini 1987) A methyl group (CH3) is a group of three hydrogen atoms bound to one carbon atom. It does not exist in a stable isolated form and is transported between molecules by intermediaries such as SAMe. Methylation is the process by which this group is transferred from the methyl donor molecule to the recipient molecule. In general terms this process is central to the control of many of the intracellular pathways. Giving a methyl group to an enzyme is often the key to activating it, and thereby beginning a synthesis or degradation process elsewhere in the cell. Equally removing the methyl group will render the enzyme inactive and stop that particular pathway. Similar mechanisms are involved in the expression of genes and therefore the production of proteins within the cell. Some specific methylation reactions include the methylation of phenols which detoxify them and thereby aid in their excretion. (Stramentinoli 1987) In the context of this dissertation, methylation is also central to the metabolic chemistry of serotonin (and therefore also melatonin). The activity of both these compounds is effectively regulated by the presence of a methyl group. SAMe is synthesised from methionine, a naturally occurring amino acid. As the name implies (METH-ionine), it contains a methyl group. By utilising the energy supplied by ATP and in the presence of magnesium, it is converted into SAMe. The process is catalysed by the intervention of the enzyme MAT (methionine adenosyl