The Latest Advances In Drug Manipulations Of The I Essay Example For Students

The Latest Advances In Drug Manipulations Of The I Essay mmune SystemINTRODUCTIONIn order to provide a detailed analysis of recent pharmacological developments involving the human immune system, it is firstly necessary to introduce the innate and adaptive immune responses . Immunosuppressants and immunomodulators will be differentiated between and a selection of new and often experimental drugs belonging to each category will be provided. Specific drugs will be described including the pharmacokinetics and pharmacodynamics involved with each type. The possible clinical uses will be alluded to along with details from recent research. INNATE IMMUNITYInnate immunity is the first line of defence and comprises physical (skin), biochemical (complement, lysozyme) and cellular (macrophages, neutrophils) mechanisms (Katzung, 1998). All these mechanisms are non-specific, anti-microbial agents which work in conjunction with adaptive immune responses to provide a more effective system (Downie et. al., 1995). ADAPTIVE IMMUNITYThe adaptive immune system is split into two mechanisms: humoral immunity and cell-mediated immunity. A basic understanding of these concepts is necessary for the purpose of understanding the specific effects of different immunopharmacological agents. HUMORAL IMMUNITYHumoral or antibody-mediated immunity is associated with B-lymphocyte cells. Antigens are foreign molecules that initiate an immune response, they have inherent immunogenicity (Tortora Grabowski, 1996). Upon contact with an antigen, B-cells divide to produce a clone of plasma cells capable of the production of antibodies. Antibodies are immunoglobulins, modified blood proteins with a specific action against antigens. Five main sub-types of immunoglobulins have been identified of which IgG is the most abundant in bodily fluids (Hopkins, 1995). Several cells are known to initiate the process of plasma cell differentiation and are known collectively as antigen presenting cells (APCs) (Waller Renwick, 1994 ). We will write a custom essay on The Latest Advances In Drug Manipulations Of The I specifically for you for only $16.38 $13.9/page Order now LymphokinesThe antigen on the surface of the APC triggers TH-cells to produce hormone-like lymphokines (Lessof, 1993). Lymphokines are cytokines, regulators of the immune reactions which are produced by lymphocytes. Examples of these chemicals include interleukins, interferon and tumour necrosis factors. Their action involves the regulation of the proliferation, differentiation and activity of leukocytes (Dale et. al., 1994). The nature of lymphocyte stimulation will determine which class of immunoglobulin will be produced (Waller Renwick, 1994). The role of complement antibody-antigen complexesAntibodies have two distinct functions: to recognise and combine with an antigen, and to activate a defence mechanism for example by activating the complement sequence (Dale et. al., 1994). This sequence involves more than thirty proteins (Mollnes Harboe, 1996) and has the function of the destruction and removal of invading micro-organisms and subcellular debris and to promote clearance of antigen-antibody complexes (Dale et. al., 1994). These functions are achieved mainly via complements ability to attract leukocytes (Lessof, 1993). The interaction of antibody with specific antigen results in the formation of the antibody-antigen complex. This complex has several functions: for instance, to immobilise an antigen therefore preventing attack upon host cells, to block active toxic regions of particular bacteria, and to allow phagocytic attack. Memory cellsOnce the antigens have been destroyed the plasma cells disappear leaving a few as memory cells which enable a swift response upon second exposure to the antigen (Trounce, 1997). Memory cells are the basis of active immunisation against bacteria (Downie et. al., 1994). Humoral immunity is most efficient against antigens dissolved in body fluids, that is extracellular pathogens, primarily bacteria whereas cell-mediated immunity is most effective against intracellular pathogens such as viruses (Tortora ; Grabowski, 1996). CELL-MEDIATED IMMUNITYCell-mediated immunity is mainly concerned with T-lymphocytes. It is this form of immunity that is thought to be responsible for tissue transplantation rejection (Tortora ; Grabowski, 1996). T-cells possess receptors upon their surface which recognise antigens, these receptors are similar to the antibodies released by B-cells. Upon contact with an antigen, T-cells produce memory and effector cells as do the B-cells. However, T-cells produce a variety of effector cells (Downie et. Al., 1995). TC-cells ; TH-cells The cells produced are mainly Cytotoxic cells (TC-Cells or CD8+) or Helper cells (TH-cells, or CD4+). TC-cells recognise and destroy virally infected host cells, hence they are also known as killer-cells (Trounce, 1997). It is also thought that cancerous cells can be destroyed by the same mechanism (Dale et. al. ,1994). TH-cells release lymphokines which activate local macrophages (Waller ; Renwick, 1994). Meaning big eaters macrophages engulf micro-organisms and secrete lysosomal enzymes, complement components and some lymphokines (Dale et, al., 1994). IMMUNOSUPPRESSION IMMUNOMODULATIONBy providing an overview of the adaptive immune responses it becomes apparent that two areas of pharmacological enquiry are of interest: immunosuppression and immunomodulation. The former concept involves developing agents that suppress the immune responses. This area is important in the treatment of organ and tissue transplant rejection and also the treatment for certain diseases resulting from immune system irregularities. The latter area involves agents that augment or alter certain components of the immune system and are therefore important in cancer and AIDS management (Katzung, 1998). NEW IMMUNOSUPPRESSANTSThe prototype immunosuppressant, cyclosporine was discovered in the 1970s Almost three decades later there is much investigation into the development of novel more effective immunosuppressive drugs (Dale et. al., 1994). Traditionally immunosuppressants have been shown to be important in prolonging the life of transplanted organs. However, purely by their nature they greatly weaken the patients defence mechanism and therefore increase the risk of infection by opportunistic pathogens (Downie et. al., 1995). Traditional thinking advocates these drugs in the treatment of autoimmune diseases where the immune system produces antibodies against various self tissues (Trounce, 1997). However, new approaches (to be discussed later) prefer the use of immunomodulators to treat these disorders. Unfortunately many immunosuppressants are non-specific and lead to therapeutic inconsistencies that produce a wide range of pharmacokinetic and pharmacodynamic variations between diff erent individuals (Kahan, 1999). Thus the latest drugs are being developed with more specificity in mind. A selection of these new drugs including mycophenalate mofetil, thalidomide, sirolimus and 15-deoxyspregualin, will be provided and their mechanisms of action, when understood, described. Mycophenolate mofetilMycophenolate Mofetil (MM) is a newly developed immunosuppressant which has been proven to be promising in the management of organ transplantation. Introduced in 1997, MM has been mainly utilised in kidney transplantation treatments in conjunction with cyclosporine and corticosteroids (Hoffman Jones-Reeder, 1998). When used in the combination described, MM has substantially reduced the incidence of kidney rejection within the first six months following transplantation (Nutley, 1995). This new drug has also been the subject of studies involving liver transplantation where it proved to reduce the incidence of rejection when combined with tacrolimus and steroids without increasing the risk of secondary infections (Jain et. al., 1997). In comparative trials with azathioprine, MM has proved to be more selective and effectively decreases episodes of rejection in renal transplant patients (Barron, 1996). In animal studies MM has been used successfully for heart and pan creatic cell transplantation but further trials are needed to prove efficacy before use on human patients. (Saltiel, 1994). Other recent studies involve the use of MM to treat autoimmune diseases such as rheumatoid arthritis (Dureza et. al., 1999). Isolated from the mould penicillum glaucum (Katzung, 1998), MM, brand name cellcept, has greatly improved the ratio of immunosuppressive activity versus side effects (Hoffman Jones-Reeder, 1998). Administered orally, MM is hydrolysed to the active metabolite mycophenolic acid in the liver and gastro-intestinal tract and excreted by the kidney in urine. (Barron, 1996). By inhibiting nucleic acid synthesis via only the de nova pathway, MM can selectively inhibit T and B-cell activity (Saltiel, 1994). The result of this action leads to the prevention of T and B-cell proliferation, the inhibition of antibody formation, and the reduction of leukocyte migration to inflammatory sites common in graft rejection. .u02a677be4e8f657e20d3ba3c25e8c6be , .u02a677be4e8f657e20d3ba3c25e8c6be .postImageUrl , .u02a677be4e8f657e20d3ba3c25e8c6be .centered-text-area { min-height: 80px; position: relative; } .u02a677be4e8f657e20d3ba3c25e8c6be , .u02a677be4e8f657e20d3ba3c25e8c6be:hover , .u02a677be4e8f657e20d3ba3c25e8c6be:visited , .u02a677be4e8f657e20d3ba3c25e8c6be:active { border:0!important; } .u02a677be4e8f657e20d3ba3c25e8c6be .clearfix:after { content: ""; display: table; clear: both; } .u02a677be4e8f657e20d3ba3c25e8c6be { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u02a677be4e8f657e20d3ba3c25e8c6be:active , .u02a677be4e8f657e20d3ba3c25e8c6be:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u02a677be4e8f657e20d3ba3c25e8c6be .centered-text-area { width: 100%; position: relative ; } .u02a677be4e8f657e20d3ba3c25e8c6be .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u02a677be4e8f657e20d3ba3c25e8c6be .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u02a677be4e8f657e20d3ba3c25e8c6be .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u02a677be4e8f657e20d3ba3c25e8c6be:hover .ctaButton { background-color: #34495E!important; } .u02a677be4e8f657e20d3ba3c25e8c6be .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u02a677be4e8f657e20d3ba3c25e8c6be .u02a677be4e8f657e20d3ba3c25e8c6be-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u02a677be4e8f657e20d3ba3c25e8c6be:after { content: ""; display: block; clear: both; } READ: Alice's Journey to Find Her Identity EssayThe adverse effects associated with MM are mainly gastro-intestinal and include nausea, diarrhoea and vomiting (Barron, 1996) thus use in patients with known gastro-intestinal complaints should be carefully considered. As with all immunosuppressants, there may be an increased risk of secondary infection but MM does not appear to be a greater threat in this regard compared to the older more conventional drugs. It is as yet unknown if MM may be teratogenic in humans as it has been in some animal studies thus use in pregnancy is ill advised unless the potential benefit to the mother outweighs the risk to the unborn child (Barron, 1996 ). It has also been noted that there is an increased risk of the development of lymphoma and other malignancies with MM treatment which is again common with many of the immunosuppressants (Nutley, 1995). This new drug certainly appears to present less side-effects when compared to traditional immunosuppressive agents. The major drawback associated with MM is the high cost: almost five times that of the traditional immunosuppressant azathioprine. However, considering that one half of kidney transplant patients experience acute episodes of rejection during the first year after transplantation (Nutley, 1995) it would appear that the cost could be well spent in terms of the saving of lives and prevention of suffering. 15-deoxyspergualin15-Deoxyspergualin (DSG) is isolated from bacillus laterosporus and has been successful in the prevention of renal transplant rejection, and may also be beneficial in heart and pancreatic transplantations (Katzung, 1998). Recent studies have shown DSG to have a unique ability among immunosuppressive drugs to reduce long-term survival and functional tolerance of discordant islet xenografts (Thomas et. al., 1995). The potential of DSG as a treatment for autoimmune diseases is also being investigated (Tepper et. al., 1995). Indeed, DSG is proving more effective than tacrolimus (Grebenau, 1999) and less toxic than aziathropine (Thomas, 1995). The mechanisms of action are not entirely understood but appear to result from the suppression of both the humoral and cell-mediated immune responses (Tepper et. al., 1995). It appears that this new drug needs further rigorous testing but possible future applications particularly in xenografts seem to be encouraging. SirolimusSirolimus (rapamycin) is relatively similar to the more traditional immunosuppressants: tacrolimus and cyclosporine. However, it is much more potent and has distinct uses in the management of kidney and heart allografts (Katzung, 1998). Again, the possibilities of sirolimus as treatment for autoimmune diseases is currently being investigated (Grebenau, 1999) and the drug is currently in phase three trials. The mechanism of action is through cytokine signals which are required for T-cell proliferation (Valantine Schroeder, 1995), that is, Sirolimus acts as a T-cell inhibitor when used in combination with cyclosporine and steroids (Bertolatus, 2000). Major side effects include increased blood cholesterol and triglyceride levels, leukopenia (decreased white blood cell count) and thrombocytopeania (decreased platelet count) (Kelly, et. al., 1997). ThalidomideThalidomide has a problematic history as it produced severe teratogenic effects when used to alleviate diarrhoea and nausea in pregnant women. However, it has since emerged as an immunosuppressant particularly useful in treatments to prevent lung transplant rejection (Katzung, 1998). Thalidomide may also prove beneficial in the treatment of HIV patients particularly those suffering from chronic weight loss as it increases the immune chemical, tumour necrosis factor-alpha (Kahan, 1999).However, mechanisms of action are not further understood and may involve a change of T-cell response to antigens (Katzung, 1998). Treatment of leukaemia is another area of possible thalidomide use (Grebenau, 1999). Obviously, this drug must not be used in the treatment of pregnant women and may also cause side-effects such as drowsiness and skin rashes (Kahan, 1999). Antibodies as immunosuppressantsMilstein and Kohler increased the pharmacological use of antibodies as immunosuppressants via hybridoma technology. This concept involves the fusing of antibody-forming and plasmacytoma cells to produce the required antibody for cloning (Katzung, 1998). The implications of such technology are far-reaching as specificity will be greatly increased using these monoclonal antibodies. As yet studies into treatments for multiple sclerosis using this technology have been inconclusive but appear to be fraught with unintended side effects (Panitch, 1996). Antilymphocyte antibodies have been utilised early after organ transplantation and have had beneficial short term effects but the long term outcomes have been disappointing (Valantine ; Schroeder, 1995). IMMUNOMODULATIONThe immunomodulation branch of pharmacology involves boosting the immune system rather than suppressing it, by using agents to augment the immune response. The potential uses of immunomodulation include the treatment of immunodeficiency disorders, chronic infectious diseases, cancer and AIDS (Katzung 1998). Many cancer patients do not die directly from their cancer but from a secondary infection. It has also been discovered that in the United States of America sixty-five million people suffer from a dysfunctional immune system which can lead to chronic viral infections, AIDS, cancer and autoimmune diseases (Beardsley, 1997)Immmunomodulation ; autoimmune diseaseTraditionally, it has been thought that stimulating the immune system will be harmful for sufferers of autoimmune disorders as it will exacerbate the bodys attack upon self cells. However, recent research suggests that autoimmune diseases maybe due to the dysregulation of the immune system, and that poor thymus functioning results in T4Helper cells losing control of humoral immunity so that antibodies lose their specificity and attack host cells (Beardsley, 1997). Thus immunomodulation in this area could be highly effective. It must be stated that this is merely a theory and that extensive testing is still needed in this area before such drugs can be used safely to treat these disorders. It would appear that immunomodulation is a new and exciting area to be explored with many potential benefits. A selection of these new drugs including levamisole, thymic peptides, roquinimex, and cyclophosphamide will be described in more detail. LevamisoleLevamisole (eramisole) is an immunomodulating agent administered orally with the effect of increasing the number of T-cells. It has been shown to be effective in the treatment of Hodgkins disease, and is approved by the FDA for the treatment of colorectal cancer after surgery. Recently, levamisole has been tested in the treatment of rheumatoid arthritis with some efficacy. The side effects involved include mild nausea, stomach pain, dizziness, headache and fatigue (Katzung, 1998). It would appear that there is insufficient research concerning this drug, thus the likelihood that it will be marketed for clinical use in the near future is markedly reduced. Thymosin other thymic peptidesThymic activity is critical to T cell maturation, only mature cells can effectively combat cancer cells and infectious agents. Thymosin conveys specificity to immature lymphoid stem cells and therefore increases the number of active T-cells (Katzung, 1998). However, it has not been yet approved by the FDA (Beardsley, 1997) despite its successes in trials in treatment of diseases of T-cell deficiency such as DiGeorges syndrome (Katzung, 1998). Thymic protein A has proved beneficial in the treatment of hepatitis C, cancer and certain immune disorders via the stimulation of the cell mediated immune system (Beardsley, 1997). Thymopentin and Thymic humoral factor have also been used to treat AIDS as well as cancer and hepatitis. However, other trials suggest that thymosin may stimulate the pituitary-adrenal system, resulting in an increase of serum corticosteroids and the decrease of thymic hormone production. Therefore the impairment of the immune functioni ng will result from thymic treatments rather than the intended increase of the immune response (Bard et. al., 1990) Such new immunomodulators certainly need extensive research before a more suitable form can be identified. CyclophosphamideCyclophosphamide (cytoxan, neosar) is traditionally an immunosuppressant used to suppress a variety of humoral and cell-mediated immune functions (Dale et. al., 1994). However, new developments have proved the immunomodulating function of the drug. Low doses given prior to immunisation with a tumour vaccine can augment the immune response (Katzung, 1998). As such, cyclophosphamide can be used to treat Hodgkins disease, lymphomas, leukemias and other tumours. Rheumatoid arthritis can also be treated by the immunomodulating features of this drug which can be achieved at higher doses than are necessary for immunosuppression (Shorthouse, 1996). Recently, this drug has been used in trials to treat chronic -progressive multiple sclerosis. However, the be nefits proved to be inadequate in balance with the side-effects which included hair loss, fever, oral ulcers (Panitch, 1996), nausea, vomiting, thrombocytopenia, leukopenia and anorexia (Shorthouse, 1996). Teratogenic effects make the drug unsuitable for pregnant or breast feeding women and long term toxicities include bladder cancer and acute nonlymphocytic leukemia (Panitsh, 1996). In conclusion it appears cyclophosphamide may have some benefit in short-term immunomodulation, particularly as a cytotoxic agent, but long term, high doses will produce a plethora of side effects. .u497a498383f6eb84b93ea35fd8c41c4b , .u497a498383f6eb84b93ea35fd8c41c4b .postImageUrl , .u497a498383f6eb84b93ea35fd8c41c4b .centered-text-area { min-height: 80px; position: relative; } .u497a498383f6eb84b93ea35fd8c41c4b , .u497a498383f6eb84b93ea35fd8c41c4b:hover , .u497a498383f6eb84b93ea35fd8c41c4b:visited , .u497a498383f6eb84b93ea35fd8c41c4b:active { border:0!important; } .u497a498383f6eb84b93ea35fd8c41c4b .clearfix:after { content: ""; display: table; clear: both; } .u497a498383f6eb84b93ea35fd8c41c4b { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u497a498383f6eb84b93ea35fd8c41c4b:active , .u497a498383f6eb84b93ea35fd8c41c4b:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u497a498383f6eb84b93ea35fd8c41c4b .centered-text-area { width: 100%; position: relative ; } .u497a498383f6eb84b93ea35fd8c41c4b .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u497a498383f6eb84b93ea35fd8c41c4b .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u497a498383f6eb84b93ea35fd8c41c4b .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u497a498383f6eb84b93ea35fd8c41c4b:hover .ctaButton { background-color: #34495E!important; } .u497a498383f6eb84b93ea35fd8c41c4b .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u497a498383f6eb84b93ea35fd8c41c4b .u497a498383f6eb84b93ea35fd8c41c4b-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u497a498383f6eb84b93ea35fd8c41c4b:after { content: ""; display: block; clear: both; } READ: Observation Report of A Child At Elementary School EssayTHC marijuanaTrials in the United States of America in 1995 have tested the use of marijuana in immunomodulation. THC is the component of interest in marijuana which has been demonstrated to enhance the production and release of pro-inflammatory cytokines from macrophages. The study has also found impairment of immunological functions in persistent marijuana smokers. However, the conclusion is that THC is an excellent tool for studying the mechanisms of immunomodulation, especially altered susceptibility to microbial infection (Friedman et. al., 1995) but further intensive study is needed. RoquinimexRoquinimex (linomide) is not an immunosuppressant, it activates lymphocyte and natural killer cells, therefore acting as an immunomodulator (Panitch, 1996). By stimulating a variety of B and T-cell functions it has been used to treat acute and chronic relapsing multiple sclerosis, with a marked reduction in relapses, disease activity and progression (Katzung, 1998). Although the mechanisms of action themselves are not fully understood it is thought that via activating T-cells these drugs stimulates the production of regulatory cytokines that suppress inflammation and prevent myelin deterioration (Panitch, 1996). Trials in prostate tumour treatment have proved that roquinimex is the most effective drug with a sixty-nine percent inhibition of tumour growth (Joseph ; Isaccs, 1998). Thus roquinimex is emerging as a promising new treatment for cancer and multiple sclerosis. CONCLUSIONTo conclude, recent literature suggests that research into immunosuppression is more wide spread than in the area of immunomodulation. This newer concept certainly needs further investigation but has many potential benefits especially in the treatment of AIDS. Many other agents such as new vaccines and alternatives to antibiotics are being developed, unfortunately due to certain constraints they are beyond the scope of this review. As understanding of natural immune mechanisms is increased, further manipulation of the immune system will be possible. As the millennium begins it appears that the future of immunopharmacology is promising. REFERENCESBard, D.R; Knight, C.G. ; Page-Thomas, D.P. (1990) A Chelating Derivative of Alpha-Melanocyte Stimulating Hormone As A Potential Imaging Agent For Malignant Melanoma AT ;a href=http://www.Biosyna.com/patent.htm;http://www.Biosyna.com/patent.htmBarron, K. (1996) Mycophenalate Mofetil (Cellcept) A New Immunosuppressant Agent AT ;a href=http://dacc.bsd.uchicago.edu/drug/bulletins/No196.html;http://dacc.bsd.uchicago.edu/drug/bulletins/No19 6.htmlBeardsley, T. R; Pierschbacher, M. ; Wetzel, G.D. (1997) Thymic Protein A: Its Development May Signal A New Tool For Rejuvenating Immune Function AT ;a href=http://www.lef.org/magazine/mag97/july_report97.html;http://www.lef.org/magazine/mag97/july_report97.htmlBertolatus, A. 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(1994) New Immunosuppressive Drugs: Focus On Mycophenolate Mofetil AT ;a href=http://www.centerspan.org/pubs/news/sp94h.htm;http://www.centerspan.org/pubs/news/sp94h.htmShorthouse, R. (1996) Cyclophosphamide (cytoxan, neosar) AT ;a href=http://www.aidsinfonyc.org/network/access/drugs/cyclop.html;http://www.aidsinfo nyc.org/network/access/drugs/cyclop.htmlTepper, M.A; Nadler, S.G; Esselstyn, J.M. ; Sterbenz, K.G. (1995) Deoxyspergualin Inhibits Kappa Light Chain Expression in 707/3 Pre-B Cells by Blocking Lipopolysaccharide-induced NT-Kappa_Beta Activation IN Journal of Immunology Vol.155, No.05, pp2427-2436. Thomas, F; Pittman, K; Ljung, T. ; Cekada, E. (1995) Deoxyspergualin is a Unique Immunosuppressive Agent With Selective Utility in Inducing Intolerance to Pancreas Islet Xenografts. AT ;a href=http://www.insulinfree.org/immunabstracts/ecarolin2.htm;http://www.insulinfree.org/immunabstracts/ecarolin2.htmTortora, G.J. ; Grabowski, S.R. (1996) Principles of Anatomy ; Physiology (8th ed.) Harper Collins: New YorkTrounce, J. (1997) Clinical Pharmacology For Nurses (15th ed.) Churchill Livingstone: EdinburghValantine, H.A; Schroeder, J.S. (1995) Ten Recent Advances in Cardiac Transplantation AT ;a href=http://www.nejm.org/content/1995/0333/0010/0660.asp;http://www.nejm.org/content/1995/0333/0010/0660.aspWaller, D. ; Renwick, A. (1994) Principles of Medical Pharmacology. Bailliere Tindall: LondonBIBLIOGRAPHYBirchall, N; Orlow, S.G; Kupper, T. ; Pawelek, J. (1991) Interactions Between Ultraviolet Light ; Interleukin-1 On MSH Binding in Both Mouse Melanoma ; human Squamous Carcinoma Cells AT ;a href=http://www.biosyna.com/patent.htm;http://www.biosyna.com/patent.htmBrazelton, T.R; Shorthouse, R; Huang, X. ; Morris, R.F. (1997) Efficacy of Immunosuppressive Agents Corresponds to their Ability to Maintain Graft Donor Phenotype in a Model of Chronic Lung Rejection :a Novel Mechanism of Immunosuppressive Drug Action? AT ;a href=http://www.astp.org/abstracts97/ph556623.htm;http://www.astp.org/abstracts97/ph556623.htmDuvaux-Miret, O; Stefano, G.B; Smith, E.M; Dissous, C. ; Capron, A. (1992) Immunosuppression In The Definitive ; Intermediate Hosts of the Human Parasite Schistosoma Mansoni by Release of Immunoactive Neuropeptides AT ;a href=http://www.biosyna.com/patent.htm;http://www.biosyna.com/patent.htmGhanem, G; Verstegen, J; Libert, A; Arnould, R. ; Lejeune, F. (1989) Alpha-Melanocyte-Stimulating Hormone Immunoreactivity in Human Melanoma Metastases Extracts AT ;a href=http://www.biosyna.com/patent.htm;http://www.biosyna.com/patent.htmGore, M. ; Riches, P. (Eds) (1996) Im munotherapy in Cancer. Wiley: ChichesterHolman, M.J; Ahsan, N; Dhillon, S; OBrien, B. Yang, H.C. (1997) A Randomised, Prospective, Comparative Study of Tacrolimus Mycophenalate Mofetil Neoral Mycophenalate Mofetil in Kidney Transplantation AT a href=http://www.a-s-t.org/abstract97/ph281378.htmhttp://www.a-s-t.org/abstract97/ph281378.htmJoyce, D. Pederson, K. (1998) Immunopharmacology: Proposed Honours Prospects for 1998 AT a href=http://www.pharm.uwa.edu.au/aussie/honours/himmun.htmlhttp://www.pharm.uwa.edu.au/aussie/honours/himmun.htmlKahan, B. D. (1998) History of Immunosuppression AT a href=http://surgery.uth.tmc.edu/organ_transplant/historyimmu.htmlhttp://surgery.uth.tmc.edu/organ_transplant/historyimmu.htmlNijkamp, F.P. Parnham, M. J. (1999) Principles of Immunopharmacology AT a href=http://www.springer_ny.com/catalog/np/mar99np/3-7643-5780-0.htmlhttp://www.springer_ny.com/catalog/np/mar99np/3-7643-5780-0.htmlSchultze, J. Johnson, P. (1999) A Stimulating New Target for C ancer Immunotherapy IN The Lancet vol. 354, Oct. 9, 1999, pp1225-1226Stadtlander Drug Distribution Co. 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Management of Operations Supply Chain Management in Nintendo

Management of Operations Supply Chain Management in Nintendo Executive Summary In every organization operations management processes play a pivotal role in promoting the effectiveness of every activity in the firm. This study gives an analysis of the management operations in Nintendo. This is a company which is involved in the manufacture and sale of entertainment products all over the world.Advertising We will write a custom essay sample on Management of Operations: Supply Chain Management in Nintendo specifically for you for only $16.05 $11/page Learn More The company’s effective operations management has significantly contributed to its success. In this case, the study will concentrate particularly on the supply chain operations involved in the company. This study begins with a brief overview of the company in question. This is followed by a critical analysis of the supply chain processes involved in the company. Finally, the study concentrates on the literature on the topic. Introduction Operations manageme nt refers to the management process associated with effective management of the activities which are involved in the production of goods and services in an organization. In every organization, the operations management managers play a very important role in facilitating the effectiveness of the organization. The major roles in operations management involve management and designing business processes and activities that are involved in production of the goods and services. In addition, operations management is also involved in management of materials, information, people and all the equipments which a business needs in production and delivering of the goods and services. One of the main operations aspects is the supply chain management. Supply chain management can be viewed as the network of the facilities and distribution options that are involved in the material procurement processes, conversion of the same to finished goods as well as distribution of these products in the market s o as to reach the customers at the right time, place, and form. In every organisation, the effectiveness of the supply chain management plays a very important role in facilitating the success of an organization. Strategic Goals and Objectives Nintendo has several objectives on which its future success is based. One of the main objectives of the company in the chain management is to reach as many people as possible in the near future without using the middle men in these operations. The company also intends to saturate its market with distribution centres where customers will be able to access the products without necessarily going through the middlemen. The last main objective of the company is to supply in the market price competitive products.Advertising Looking for essay on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Company Overview Nintendo is one of the most successful multinational companies involved in the manufacture and sale of the entertainment products. Nintendo Company was founded by Yamauchi in 1889. Since then, this company has been dealing with manufacturing and marketing of entertainment products (Cohen 2009: 57). Nintendo is the longest running company in the industry of video game market (Anonymous, not dated par 2). The company has also dominated the market for a long period.  The company covers a significant market area in the world. It plays a significant role in maintaining economic stability. This is through employment creation and philanthropic activities. Over the past, this company has recorded a recommendable performance in terms of return. For instance, the company recorded revenue of 9.9 % increase in the year 2009 (Research Markets 2010: par 3). This was equivalent to an increase of 8.5% in profits. Nintendo’s Supply Chain As already noted, the supply chain is very important in any organization. Nintendo has a clear supply chain which has contrib uted to the company’s success. The organization of the supply chain operations plays a pivotal role in determining the success of an organization. Although the company has not exhaustively covered the global market, it has several centres in different countries which act as the centres of distribution in various countries. In America, the distribution centre is located in the North Bend (Jeff 2010, par 2). This is one of the most successful distribution centres for the company. The facility has been installed with the modern technology equipments, which has significantly increased its efficiency. Production activities take place at Japan after which the products are passed to various distribution centres. It is from these centres where the products are distributed to various parts to reach the customers.  In the chain distribution, the company’s distribution centres have the responsibility of ensuring that there is no variation between the orders and inventories. In other words, the distribution plays a major role in prediction of demand so that there is no excess or shortage in the supply chain. Wrong demand prediction can cause a company great losses through stock accumulation. Shortages can also lead to loss of customers.  Due to the company’s modernized distribution centres, it has been awarded as the best ware house of the year (Jeff, 2010: par 5). The company was recognized as one of the best performing in terms of customer satisfaction and services.Advertising We will write a custom essay sample on Management of Operations: Supply Chain Management in Nintendo specifically for you for only $16.05 $11/page Learn More This was characterized by high level of communication which eased the interaction between the customers and the suppliers. This ensured a clear supply chain process, which led to maximum consumer satisfaction. Over the past, the company has made several changes in the distribution process in an attempt to improve its services to the public. The Ordering Process The ordering process at Nintendo has improved drastically over the past. The company has adopted an automation of the ordering process. The automation of the ordering process in particular has increased the efficiency of the ordering process, which has enormously reduced the ordering costs. Nintendo America is one of the company’s centres which have recorded a recommendable performance in this field. This ware house has been completely automated, a thing that has eliminated the paperwork in the ordering process hence increasing the level of efficiency (Jeff 2010, par 6). Internet in Supply Chain In the contemporary business world, the internet has played a pivotal role in promoting the effectiveness of operations. Nintendo has integrated internet technology in the distribution chain. This has significantly contributed to improvement of the supply chain. Integration of internet in the supply chain operation s has a significant implication in reducing inventory requirements. Embracing the modern technology and internet in the supply has led to improvement of the supply chain in the company through various ways. First, the company has an opportunity to build a strong collaboration between the company and the members in the channel. We will also be able to reach our customers directly by eliminating the middlemen. Market Analysis Over the past, this company has been struggling to extend its services as wide as possible. One of the major steps which this company has ever taken in its efforts to diversify its market was in 1980 when it developed new markets for its products in United States. At the United States, the company launched subsidiary Nintendo of America Inc. in New York where the company recorded large sales.Advertising Looking for essay on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Meanwhile, the company made another innovation by introducing a portable video game (Jorg: 2029, 2009). This boosted the rate of development of its new market in U.S. From this point, Nintendo Company continued to expand in the global market, the fact which encouraged the company to invent more in the entertainment industry. Weaknesses in the Supply Chain Although the company has recorded a recommendable performance in terms of innovativeness, it has failed to satisfy its market. For instance, people have been complaining of shortages of Wii in some parts of the world. Although it has recorded several achievements, the company has some areas of weaknesses. These weaknesses have to some extent affected the company’s efforts to move forward. The first weakness of the company is its poor performance in handling online games where the competitors have recorded a better performance (Nick, 2010). This has undermined the reputation of the company in this field. We will try to improv e our supply chain efficiency on a continuous basis. We will collaborate with our suppliers to design new products and to reduce the time it takes to get new products into the production.  One of the main threats of the company is the presence of their competitors. In 1994, Sony’s entry in the market posed a great threat to our company. Soon after its entry into the market, Sony introduced a console which was more advanced than ours. This product posed a threat to the survival of our product in this field. Achievements of Nintendo in the Supply Chain Operations One of the main strengths of this company is its innovativeness (Popular Science, 2004, par 3). Over the past, the company has managed to eliminate monotony through frequent introduction of new products in the market. For instance, we recorded tremendous increase in sales after introducing Wii in the market. This high rate of innovations has been facilitated by intensive research. Our company has enjoyed various thin gs in the video games market over the past. One of the main opportunities of our company is its ability to detecting business opportunities (Diana: 56, 2010). For instance, rather than production of video games only, the company once attempted to conduct a taxi business and a hotel. The company pays much attention on new opportunities. This has contributed significantly to the success of the company.  We as a company has realized the necessity of paying more attention to the part of the population which does not use pour games. This opportunity has helped the company to increase the total sales significantly. Many companies have been making the mistake of overemphasizing on the maintenance of existing customers but paying little attention in the efforts to find new customers. In other words, our company has done enormously well in terms of market expansion. This attribute has played a major role in defeating our competitors. Literature Review The supply chain can be seen as a seri es of cycles which involves communication between the buyer and the seller (Chopra Meindl, not dated: par 7). The supply chain can be viewed in terms of their main processes. These include the Customer order cycle, Replenishment cycle, and the Manufacturing cycle. In the contemporary business world, the supply chain operations have undergone significant changes through technological developments. However, several companies have dipped into problems by adopting the new technology without making necessary arrangements, the fact which has made them to incur huge losses (Epiq, 2010: par 2). For instance, several companies have ended up spending more buy adoption of some of the procurement software due to ignorance (Epiq, 2010: par 2). However, these negative impacts can be overcome by adoption of these new methods slowly rather than just abruptly. This will enable an organization to make the necessary changes. A cycle view is very important while viewing the company’s supply cha in operations. The cycle view of the company’s supply chain helps an organization to define the processes involved in production and the owners of each process (Anonymous, 2011: par 9). The processes involved in the customer order cycle engrosses the customer arrival among others. Customer arrival implies that the customer reaches the location where they can access the choices available. In this case, the customer makes the necessary choice of the products they want. For Nintendo, this step involves selection of the entertainment product which is available from the distribution centres. In the customer order entry process, the customer informs the seller of the goods they want to purchase. This process also involves allocation of the products to the consumers. In case of the Nintendo Company, the customers receive the entertainment products from the distribution centres depending on what they have ordered and their location. The last step in this process is customer order rec eiving. It involves the delivery of the product to the customer. The cycle view of the company’s supply chain is very important especially when making decisions concerning the operations of an organization. However, this process may need some changes depending on the changes in the supply chain. For instance, the company is supposed to make appropriate changes in case the level of demand increases in order to satisfy new demand. Overview of the Models of Supply Chain Management Level one of the Supply Chain Operations Reference (SCOR) model, involves the planning and management of demand and supply. At this level, this company establishes the relationship between the resources and what is required. This aims at finding whether the two are equal. This helps in planning the demand and supply chain. This also includes management of the business rules. For instance, the increase in the demand in this company will disturb the equilibrium between the resources and demand. Demand wi ll exceed the resources. In some cases, the company may be required to make changes in terms of its product design and sales and support. For instance, more efficient ways may be employed in the sales support. This increases the ability of the organization to deliver more products within a short time. This will help in meeting the increased level of demand. The SCOR framework focuses on the implementation of the cross-sectional processes in the supply chain management (Lambert, 2008: 313). DCOR model on the other hand involves research, design, integrate and amend. DCOR concentrates on the organization of the operational steps for the product development (Lambert, 2008: 313). This contributes towards the provision of quality competitive goods in the market. Supply Chain and the Company’s Competitive Advantage The supply chain operations have significantly helped Nintendo in developing its competitiveness. Through the use of the modern technology, the company has managed to re duce the expenses involved in the ordering process. When paperwork is reduced in the transaction, this saves a lot of time and financial cost reduces. This has significantly helped the company in reducing the overall operational expenses.  Through clear supply management operations, the company has also managed to satisfy its customers. This has developed a competitive advantage over the other companies which has not adopted the necessary technology on their operations. Nintendo has also maintained a high level of innovation in its production operations. This has helped the company in maintaining a high level of performance. Conclusion From the above discussion, it can clearly be seen that the operations management plays a pivotal role in every organization. The success of every activity in an organization depends on the effectiveness of the operations involved. The success of any organization will largely be determined by the effectiveness of the operations management involved. A s already seen, one of the most important operations management operations in an organization is the supply chain management. However, the company still has some room for improvement on its operations involved in its supply chain operations. The company can improve its level of technology in various fields. For instance, it can also embrace the recent technological developments to improve production as well as the supply operations. These include reduction of the paperwork by computerizing the process of sending orders. This can significantly contribute to maintaining high level of performance in its operations. Reference List Anonymous. Not dated. Nintendo: Company Profile. [Online] Available at: http: //wii.nintendolife.com/companies/Nintendo. Anonymous, 2011. Supply Chain Management. [Online] Available at: scribd.com/doc/13821319/Notes-on-Supply-Chain-Management. Chopra, S. and Meindl, P. Not dated. Supply Chain Management. [Online] Available at: princesoft.ro/wiki.aspx?title=sup ply%20chain%20management . Cohen, D. 2009. Classic Video Games Blog. [Online] Available at: http://classicgames.about.com/b/2009/01/20/nintendos-founder-fusajiro-yamauchi-and-375-years-of-breaking-records.htm. Diana, D. 2010. The Right Sensory Mix: Targeting Consumer Product Development Scientifically. Netherlands: Springer Epiq. 2010. Supply Chain Operations. [Online] Available at: http: //www.epiqtech.com/supply_chain-Operations.htm. Jeff, H. 2010. Supply chain update: state-of-the-art direct distribution at Nintendo of America. [Online] Available at: bus.wisc.edu/grainger/newsletter/pdfs/may2001.pdf. Jà ¶rg, Z. 2009. Wii Innovate How Nintendo Created a New Market Through the Strategic Innovation Wii. Germany: GRIN Verlag. Lambert, D. 2008. Supply chain management: processes, partnerships, performance. USA: Supply Chain Management Inst. Nick, S. 2010. Nintendos Online Weakness Is a Big Turn-Off for Developers. [Online] Available at: businessinsider.com/nintendos-online-weakness- is-a-big- turn-off-for-developers-2010-1. Popular Science, 2004. Top 100 tech innovations 2004, Vol. 265, No. 6, ISSN 0161-7370, Bonnier Corporation. [Online] Available at: https://books.google.com/books?id=fwAAAAAAMBAJdq=Weaknesses:+Nintendo+Co.,+Ltd.source=gbs_navlinks_s. Research and Markets, 2010. Nintendo co., ltd. -SWOT analysis. [Online] Available at: researchandmarkets.com/reports/570207/ . Slack, N. 2004. Operations Management. (U.K.): Pearson Education, Limited,

IMPACT OF MORE ACCOUNTING INFORMATION Essay Example | Topics and Well Written Essays - 3000 words

IMPACT OF MORE ACCOUNTING INFORMATION - Essay Example The impact of more accounting information will be discussed in relation to the users of the financial statements such as the shareholders, suppliers, customers and creditors. Likewise, the impact of more accounting information when used by the competitors (Molloy and Molloy, 1996) or employees will also be discussed. Considerations of future situations tend to affect conventional accounting, although using elements of the future forms an essential component of the accounting structure. The financial standard of decision relevancy of accounting (Weston and Brigham, 1993), generally agreed to be a primary factor that gives societal value to accounting, may be weakened by the search for a more trustworthy accounting procedure. One of the best techniques in accounting would be to incorporate aspects of future values without leaving too many degrees of freedom for manipulating the data. The aim is thus to keep accounting credible, and yet predictable and even if more accounting informatio n becomes available, all aspects of the information will have to be considered, before any final conclusion is drawn on the advantages or disadvantages of the accounting information. ... The financial statements are audited by external auditors (Whittington and Pany, 1995) either chartered accountants or certified public accountants in order to give credibility to the statements. All companies are required to give financial statements to its shareholders, suppliers, creditors, employees, managers, board of directors, government regulating bodies and the like in order to ensure that the company does not violate any corporate laws and that they remain accountable to their stakeholders and financiers. The financial statements are important tools for decision making and determine company management policies and thus accounting forms the basis of any corporate management decision making. There have been arguments on incorporating additional estimates or forecasts of the future into financial statements and providing estimates of future cash flows. This may in turn be considered alongside some sensational corporate scandals, for companies located in the US, which have been focused on reducing the power of managers which could engage in fraudulent behavior and accounting manipulation of assets, liabilities and capital. A more reliable and validated or trustworthy figures on the balance sheet is expected and income statement accounts have been implemented by new and more complicated monitoring and inspection processes. As to how far this can be achieved can be studied by using market values in accounting reports. The Generally Accepted Accounting Principles (GAAPs) in a number of countries contain elements of the market values of assets and liabilities. To illustrate, International Accounting Standards (IAS), U.K., and U.S. GAAPs require financial investments that are not long-term investments,