Vitamin D as Hormone Essay Example for Free

Vitamin D as Hormone Essay INTRODUCTION: Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. Vitamin D is thus not a true vitamin, as it can be synthesized in adequate amounts by most mammals exposed to sunlight (cats and dogs cannot synthesize vitamin D and must receive it in their diet). An organic chemical compound (or related set of compounds) is only scientifically called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from their diet. However, as with other compounds commonly called vitamins, vitamin D was discovered in an effort to find the dietry substance that was lacking in a disease, namely, rickets, the childhood form of osteomalacia. ROLE OF VITAMIN D IN REGULATION OF SEVERAL GENES: The vitamin D hormones have essential roles in human health. Vitamin D hormones act by binding to and activating the vitamin D receptor (VDR) to regulate the expression of genes in a tissue-specific manner. Vitamin D hormones regulate blood calcium levels by controlling intestinal absorption of dietary calcium and reabsorption of calcium by the kidneys. Concomitantly, vitamin D hormones also suppress the production of the calcium regulating hormone, parathyroid hormone (PTH), which is produced by the parathyroid glands. The vitamin D hormones also participate in the regulation of cellular differentiation and growth, as well as bone formation and metabolism. Additionally, vitamin D hormones are required for the normal functioning of the musculoskeletal, immune and renin-angiotensin systems. There is a growing body of evidence linking vitamin D insufficiency with cognitive and neural dysfunction. The widespread beneficial effects of vitamin D hormones are continually being elucidated through studies directed to the intracellular VDR and the corresponding networks of VDR-responsive genes in nearly every human tissue. It is becoming evident that vitamin D insufficiency has a widespread and significant impact on a number of key physiological systems. METABOLISM OF VITAMIN D: Both forms of vitamin D undergo identical metabolism . Some evidence indicates that vitamin D2 may be metabolized more rapidly than vitamin D3, but with regular daily intake they can be considered bioequivalent. Both forms of vitamin D are converted to 25-hydroxyvitamin [25(OH)D] in the liver, and the serum level of 25(OH) D is measured to determine the adequacy of vitamin D status. In the kidney, 25(OH)D is hydroxylated to 1, 25-dihydroxyvitamin D [1, 25(OH)2 D], which is the only biologically active form of vitamin D. Acting principally on the duodenum, 1, 25(OH)2 D increases calcium absorption. It also acts on bone cells, both osteoblasts and osteoclasts, to mobilize calcium. The synthesis of 1, 25(OH)2 D is tightly regulated and stimulated primarily by serum parathyroid hormone THE VITAMIN D RECEPTER AND MECHANISM OF ACTION: The vitamin D system is unique in that distinct calcium homeostatic functions and cell growth regulatory activities are mediated through a single ligand, calcitriol, acting through a specific receptor exhibiting ubiquitous tissue expression, the vitamin D receptor (VDR). The VDR is a member of a superfamily of nuclear steroid hormone receptors which regulate gene transcription by interacting with response elements in gene promoters. Structure-function analysis of the VDR protein has defined distinct domains involved in DNA binding, ligand binding, receptor dimerisation and gene transactivation, including a C-terminal activation function domain (AF-2) that is important for cofactor interaction. A model for regulation of gene transcription by the VDR is evolving and proposes VDR interaction with various components of the basal transcriptional machinery, including newly defined coactivators and corepressors, which may act to regulate gene transcription by altering histone acetylation and chromatin structure. This review describes the vitamin D endocrine system and the role of the VDR in regulating this system, including the molecular basis for the diverse actions of synthetic calcitriol analogues in the treatment of autoimmune disease and cancer. ROLE OF VITAMIN D AS HORMONE Vitamin D and Bone Cell Activity: Approximately 60 genes are known to respond to vitamin D. Many of these vitamin D responsive genes are expressed by the bone forming cells (osteoblasts) which include: * type I collagen. * alkaline phosphatase, * osteocalcin * tumour necrosis factor ligand member (RANKL) Tumour necrosis factor ligand member (RANKL) is central to osteoclastogenesis. The bone resorbing cells (osteoclasts) also express vitamin D-responsive genes. It is evident that 1,25(OH)2D plays a major role in controlling osteoclastogenesis and bone resorption through its modulation of the RANKL gene in osteoblasts. Bone mineralization: These types of results are increasing interest in the view that the modulation of vitamin D activity within bone cells, either through the vitamin D receptor or metabolism of vitamin D, has effects on the levels of bone mineral. It is through such a mechanism that higher levels of vitamin D in the elderly may provide protection against hip fractures. Cancer prevention: Role of vitamin D in prostate cancer: Prostate cancer is the second leading cause of cancer deaths in men in the United States. Developing new treatment strategies is critical to improving the health of men. Our research has focused on four areas in which we have pursued the possible use of 1alpha,25(OH)(2)D(3) and its analogs to treat prostate cancer.The results of a clinical trial of 1alpha,25(OH)(2)D(3) treatment of patients with early recurrent prostate cancer. We provide preliminary evidence that 1alpha,25(OH)(2)D(3) may be effective in slowing the rate of PSA rise in selected cases of prostate cancer. In conclusion, we believe that 1alpha,25(OH)(2)D(3) has a role in thetreatment and/or prevention strategies being developed for prostate cancer. However, to increase antiproliferative potency without increasing side-effects, the use of less calcemic analogs appears to be the most reasonable approach. Role of vitamin D in breast cancer: In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention. Role of vitamin D in auto immune diseases: Vitamin D and its prohormones have been the focus of a growing number of studies in past years, demonstrating their function not only in calcium metabolism and bone formation, but also their interaction with the immune system, which is not surprising, since vitamin D receptors are expressed in different tissues, such as brain, heart, skin, bowel, gonads, prostate, breasts, and immune cells, as well as bones, kidneys, and parathyroid glands.Current studies have related vitamin D deficiency with several autoimmune disorders, including insulindependent diabetes mellitus (IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). In view of those associations, it has been suggested that vitamin D is an extrinsic factor capable of affecting the prevalence of autoimmune diseases. Vitamin D seems to interact with the immune system through its actions on the regulation and differentiation of cells like lymphocytes, macrophages, and natural killer cells (NK), besides interfering in the in vivo and in vitro production of cytokines. Among the immunomodulatory effects demonstrated we should mention: a reduction in the production of interleukin-2 (IL-2), gamma interferon (INFÃŽ ³), and tumor necrosis factor (TNF); inhibition of the expression of IL-6; and inhibition of the secretion and production of autoantibodies by B lymphocytes. Vitamin D modulation of immune responses: Dendritic cells (DCs) are primary targets for the immunomodulatory activity of 1, 25(OH)2D3, as indicated by inhibited DC differentiation and maturation, leading to downregulated expression of MHC-II, costimulatory molecules (CD40, CD80 and CD86) and decreased production of IL-12. Moreover, 1, 25(OH)2D3 enhances IL-10 production and promotes DC apoptosis. Together, these effects of 1, 25(OH)2D3 inhibit DC-dependent T-cell activation. In particular, the active synthesis of 1, 25(OH)2D3 seems to exert an autoregulatory function by inhibiting the differentiation of monocyte precursors into immature DCs and the subsequent ability of the immature DCs to undergo terminal differentiation in response to maturation stimuli. FIG. Mechanisms involved in vitamin D modulation of the immune responses. DCs are primary targetsfor the immunomodulatory activity of 1, 25(OH)2D3, as indicated by inhibited DC differentiation and maturation, together with inhibition of differentiation of monocyte precursors into immature DCs. 1, 25(OH)2D3 suppresses Th1 (and Th17)driven cytokine responses, induces Treg cells, induces IL-4 production (Th2) and enhances NKTcell function. Differentiation and maturation of B cells is also inhibited. Th are CD4+ helper cell subsets (Th1, Th2, Th3-Treg, Th17) originating from naÄ ±ve T cell (Th0). Thin arrows (left) indicate cytokines that induce differentiation of Th0 cells and thicker arrows (right) indicate cytokines produced by activated Th cell subsets. All T cells that have been tested express the VDR. B cells and NKT cells are also reported.The yellow circles indicate the cytokines/activities inhibited by vitamin D.On the contrary, the green circles indicate the cytokines enhanced by vitaminD. Conclusions: Knowledge of the physiology and pathology of vitamin D is currently increasing at a rapid rate. The realisation that vitamin D can act in a paracrine and autocrine manner in addition to its well-described endocrine action opens up considerable opportunities for the development of new understanding of the requirement for an adequate vitamin D status for optimal health. It is encouraging that the relatively simple and cheap practice of maintaining an adequate vitamin D status has the potential to provide health benefits in a number of areas, which afflict an increasing proportion of the population, as well as consume an increasing proportion of the healthcare budget to provide treatment. The reduction of the risk of hip fracture in the elderly is one such area. A high priority of research must be to identify the critical 25OHD values required to maintain a healthy skeleton in the elderly. As well research must determine whether a low vitamin D status influences the development of cancer, whether it increases the absolute risk of cancer or whether it modulates the growth or invasiveness of cancers. Clinical laboratory professionals have a responsibility to improve the precision and accuracy of current 25OHD assays in clinical use. This work will require the collaboration between the profession and instrument and reagent manufacturers. The International Federation of Clinical Chemistry and Laboratory Medicine is in an optimal position to coordinate such a project.

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The world is a puzzle and we're two pieces that fit perfectly together. Within you, I lose myself, without you, I find myself, searching to be lost again Love is like an hourglass with the heart filling up as the brain empties Immature love says: "I love you because I need you." Mature love says: "I need you because I love you." I don't need to be wanted, I want to be needed. Love is when you've ran out of excuses for hating someone. When a young man complains that a young woman has no heart, it is a pretty sure sign that she has his Love is like pizza, when it's good, it's really good. When it's bad, It's still pretty good. Absence sharpens love, but presence strengthens it Devil, don't you know you are as beautiful as an Angel? G. Leopardi In any relationship in which two people become one, the end result is two half people If you're sweet and sincere, I'll call you my dear. If you're kind and funny, I'll call you my honey. If you're caring and smart, I'll call you my sweetheart. If you posess all of the above, then you are my true love. It's easy to fall in love, but it's hard to find someone to catch you Im sweet like suger, soft like suade, but unlike nintendo i never get played Why shed tears in the pond of life when you can make a splash? Thou art to me a delicious torment. My heart is ever at your service Kiss me and you will see stars; love me and I will give them to you. Bitterness imprisons life; love releases it. Bitterness paralyzes life; love empowers it. Bitterness sours life; love sweetens it. Bitterness sickens life; love heals it. Bitterness blinds life; love anoints its eyes. It is impossible to repent of love. The sin of love does not exist. I'm in the mood for love Simply because you're near me. Funny, but when you're near me I'm in the mood for love. A kiss is something you cannot give without taking and cannot take without giving. "Where should one use perfume?" a young woman asked. "Wherever one wants to be kissed," I said.-- Coco Chanel Where one drop of blood drains a castle of life, so one kiss can bring it alive again. Some people grumble because roses have thorns. I am thankful that thorns have roses. We are each of us angels with only one wing. And we can only fly embracing each other

Making decisions Essay

Written by Bernard Malamud, â€Å"The Natural† title does place a key meaning to the term, â€Å"the natural† as it is an inspiring baseball story that places a good read. The author discusses several character traits as well as interesting characters that are found in real life. Therefore, â€Å"The Natural† represents its meaning in such a way that it portrays the natural real life characters of America. Furthermore, â€Å"The Natural† by Bernard Malamud is a work different from the rest of the literature he has written. â€Å"The Natural† is a title that portrays â€Å"the natural† baseball craze of Americans; this is something that is very â€Å"natural† in this literature because the game of baseball places a â€Å"natural† exciting feeling within the American public. The craze of the game is absolutely â€Å"natural† and therefore, the author reflects many characteristics and story plots throughout the novel. Therefore, this can be one of the reasons why the title term, â€Å"The Natural† would place the same meaning as, â€Å"the natural. † After reading through Bernard Malamud’s novel, â€Å"The Natural,† I also felt that there were mixed natural feelings of loss and victory associated with the natural life pattern. Malamud highlights on natural traits of man’s emotions throughout the novel where we experience heightened love, sense of victory as well as loss. The beginning of the novel is strange but the story slowly picks up after a span of 15 years where we see the coaches desperately trying to win the baseball game slot. At this particular stance, we sense the â€Å"naturalness† displayed in the story by the author when Roy takes a straight hit at his first ball throw that makes Roy seem very â€Å"natural† at his game. By â€Å"natural† here, we mean Roy’s fluent attempt at his game that makes him the hero of the novel. Though the psychiatrist tries to messes with his mind, a â€Å"natural† instinct is always followed by a sense that shows familiarity as well as fluency with the task that Roy is trying to accomplish. Roy is not a trained baseball player and that is the reason why we would state that Roy’s â€Å"naturalness† in his game is an attribute he has from within. The title, â€Å"The Natural† can also be related to love or infatuation that Roy develops for Memo Paris since his arrival at Knights. Love or infatuation is truly a â€Å"natural† feeling and again, the author maintains the theme of his title that precisely corresponds to the story he is narrating to his audience. Apart from the natural skill of Roy that Bernard Malamud displays in his character, we also come across the natural feeling of love in the story. â€Å"The Natural† truly places an emphasis on its title and the Bernard Malamud knows his choice of the title. â€Å"The Natural† not only displays the realistic aspects of feelings but also skills that the character in the novel is fluent in. â€Å"The Natural† as stated earlier, also displays several characters that show a natural resemblance to real life characters. It is evident to come across beautiful and wicked women in real life and thus, what we read in â€Å"The Natural† too relates to the natural life. Bernard Malamud discusses the several factors that are associated with the natural aspects of one’s life by narrating Roy’s story. Bernard has been extremely entertaining in providing a perfect baseball story that is of â€Å"natural† interest for its readers and the readers comprise of millions of American baseball fans due to the fact that American baseball is the national sport of the country. We further witness how Bernard Malamud tackles the several issues of Roy’s life naturally where victory is definitely a part of one picture and another picture that Malamud represents at the end of the story is the loss. â€Å"Nature† or â€Å"Natural† has different meanings, of which Bernard Malamud has attempted to cover most of the meanings that have been portrayed in the story. Mostly, it is the realism stance of the story that counts in the Bernard Malamud’s narration. The stance of growth and advancement, as in real life, is another sign of â€Å"naturalness† in Bernard Malamud’s text, â€Å"The Natural. † The real â€Å"natural† life also accounts for the good and the bad. We witnessed characters that came from good backgrounds as well as bad backgrounds. Therefore, the realistic â€Å"naturalism† in the novel plays a vital role in giving an insight into the title; that is â€Å"The Natural. † Overall, the themes that can be found in â€Å"The Natural† placed a natural feeling in the heart of the readers. We saw how victory takes place and how the character in the story, Roy faces defeat as well. We also come across the sense of greed that leads Roy to accepting the bribe that made his team lose. The story serves as a valuable lesson for the readers to take the actions and consequences act into account as for every action, there is a consequence. If the action is good, the consequence is good and if the action is bad, the consequence will also be the same. With regards to the title of the novel, â€Å"The Natural†, I agree with it due to its coinciding incidences with the realism of life. The author successfully draws a sense of naturalness in the entire novel thereby making the title, the perfect match for it. Including the themes of love and infatuation, Bernard Malamud completes his story by highlighting on every aspect of human emotions. Bernard Malamud’s style of presenting the story in a realistic manner pertaining to the game of baseball as well as several characters draws a tremendous interest for the readers to look into the realistic factual characters presented by him in the novel. â€Å"The Natural† is a perfect title that applauds victory and sheds light on failure; love and infatuation; the good and the bad as well as choices. This characteristic feature of the novel makes it distinct and unique, the themes of which are truly â€Å"natural† in every sense†¦ LESSON 2: TROY AND ROY COMPARISON Troy and Roy are characters that are similar as well as differ from each other in many ways. Roy had clearly been an achiever in his life, till the â€Å"almost† end. In case of Troy, we don’t see that coming in his life except before he was jailed. Instead, Troy’s life revolves much around his own family and his own past and his own emotional drama. Roy had his love and his piece of infatuation, victory, failure as well as growth throughout the story. We see the same happening in Troy’s case but with a much different note. The only similarity I found through both the characters was their aim to become a baseball player of which, Roy had achieved a permanent status of a â€Å"natural† baseball player while Troy had given up on baseball based on his age. However, in Troy’s case, we didn’t see this aim in his life. Yes- he wanted to become a baseball player, he became the best baseball player but never returned back. He lost the opportunity when he was provided with one. Roy, however, is wise while making his decisions though at the end of the story, he too loses himself towards greed. That is another part of the story. I agree that both the characters have faced setbacks and triumphs in their own way in their respective stories but they cannot be stated as the â€Å"black and white† versions of the same kind of American male. Troy is more of a confused personality who loses opportunities while Roy is an achiever and the only moment he failed was when he was presented a lofty sum by Judge to lose the game or else, it was clear that Roy would have had led Knights to the path of victory. Troy revolves much around his personal life where he is involved with his sons, Cory and Lyons with his wife Rose and his girlfriend, Alberta. His brother Gabriel has a small role to play but Troy’s feelings towards his brother Gabriel where he holds himself responsible for his misfortunes shows Troy’s naive attitude towards understanding issues. Unlike Roy (whose game and success came naturally to him), Troy has an abusive childhood who was abused by his father. Eventually, the same influence and history was repeated by Troy on his other two sons. There is no change of heart throughout the story. We also sense that though there is a considerable time lapse between the lives of Troy and Roy, age didn’t deter Roy from playing baseball again while Troy easily gave up his game. The other similarity that I can state in both the characters is the sense of moral weakness. Troy and Roy are morally weak. Troy cheated on his wife by involving himself with another woman while Roy gives himself in to the bribe by the Judge. Roy’s character is exhibited less emotionally except when he involved himself in love and infatuation. Troy’s character is more on an emotional stance where he has his life and feelings in dilemma since the beginning. Though, both the characters face their actions and their consequences in their own manner, both the stories end with a sad note; Roy with his failure and Troy with his death. However, Troy’s daughter, Raynell does seem like an angel in the story. Troy had imaginarily built fences around his relationships wanting to keep death away from those he loved and those he hated as well. He had built his own boundaries and thus, was an unsuccessful father and even an unsuccessful husband (as he cheats on his wife). Roy’s weakness lies mainly with money and love as he too had a poor childhood and therefore aimed to become a baseball star. Troy is a fifty-three year old man who has built imaginary fences around himself from everyone in his life, including his own wife and therefore cheated on her. Roy, on the other hand, didn’t cheat on him and thus, Troy and Roy cannot be regarded as the black and white versions of the same American protagonist displayed by the two authors. Troy and Roy are similar, but in a smaller sense with each other. They come across misfortunes and in the end, have a sad ending to their lives. Their emotional stance on the events they faced in their lives is different. In both the novel stories, we come across a time lapse that had passed between the characters. Roy, as I believe, is sincere in his motives and is only confused about certain issues in his life. Troy, on the other hand, does not understand the essence of life at all and proceeds with life as it is, without willing to make any changes. Roy, a personality mostly not guided and mistaken, is underestimated though he has had a few bad hits in the baseball game, based on the story. Troy has faced a long hurdle of hardships throughout, especially when he quit his career as a baseball player after going to the prison. We also witness discrimination, apartheid in August Wilson’s play, â€Å"Fences† where Troy is Black and is not promoted for a long time to the position of the driver based on his skin color. We come across no such issue of discrimination in Roy’s case but further, Roy’s foolishness to achieve the woman he wants. Roy is willing to do anything for her and therefore, blindly accepts what Judge offers and thus, lands in a situation where he is a loser. He could have been victorious only if he had used his senses in a stronger way while making decisions (and by not letting his emotional part overtake him). Troy, on the other hand, has his life in a completely irreversible state where Troy’s confidence is completely shattered by the term he spent in prison. Therefore, he couldn’t change what already happened in his life and therefore, didn’t have sufficient confidence to go back to his previous life. Troy and Roy both differ in a great respect but share only some similarities.

Techniques For Evaluating A Successful Customer Service...

1. Techniques for evaluating a successful customer service operation are as follows:- i. Commitment to Quality – ETA has set a specific standard to ensure complete customer satisfaction by reducing, eliminating many customer’s callbacks or recalls. With the help of surveys conducted and logs kept by individuals companies, the standards of the company can be revised to a level that accurately measures and improves upon customer satisfaction which can only be achieved by the data taken from tests and measurement tools that are converted into specific procedures to resolve problem and improve customer request response. The preferred response time in responding to and resolving a customer request should not be more than 24 hours. ii. Focused†¦show more content†¦Monthly or biweekly discussion groups, meetings, or seminars on performance of products or services could provide the ideas and strategies required to power the continuous improvement cycle. v. Integrity – It requires the authority and empowerment to make decisions and carry out tasks without requiring a superior’s seal of approval. The customer service agent should be able to authorize refunds, exchanges, repairs or upgrades based in established principles. This not only speeds up customer service response time, but also empowers and engages the specialist in the integral running and success of company. 2. The three distinct groups of customer service functions are – i. General Customer Support – Staffed primarily by generalists and non-technical personnel. They also provide front line assistance such as â€Å"walking† the customer through the owner’s manual, assessing the nature of interest-technical or non-technical, and responding to literature requests and other general issues. ii. Technical Customer Support – Staffed by technicians and engineers that provide technical assistance in the areas of application,installation,on-site repair and maintainance,user information, site repair and customer assistance. iii. Customer Satisfaction Monitoring – This includes surveys and asks for feedback