Anatomy and Pathophysiology of Gout and Lupus

Anatomy and Pathophysiology of Gout and Lupus Introduction Gout is an acute inflammatory arthritis with the potency to fully destroy the integrity of the joint leading to severe disability. It is termed as a true crystal deposition disease caused by formation of monosodium urate crystals in joints and other tissues. It is the common cause of inflammatory arthritis that has increased in prevalence in recent decades (Roddy and Doherty 2010). Gout normally results from the interaction of genetic, constitutional and environmental risk factors. It is more common in men and strongly age related. Both acute arthritis and chronic arthropathy (tophaceous gout) are considered under the rubric of gout (Mikuls and Saag 2006; Roddy et al. 2007). In a broader term, it can be defined as combination of events involving an increase in the serum urate concentration, acute arthritic attacks with monosodium urate monohydrate crystals demonstrable in synovial fluid leukocytes, and tophi which usually occurs in and around joints of the extremities. These physio-c hemical changes either occur separately or in combination (Terkeltaub 2003; Shai et al. 2010). Gouty arthritis accounts for millions of outpatient visits annually and the prevalence is rising. It affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Rates of gout have approximately doubled between 1990 and 2010. A number of factors have been found to influence rates of gout, including age, race, and the season of the year. In men over the age of 30 and women over the age of 50, prevalence is 2% (Eggebeen 2007). Anatomy and Pathophysiology Gouty arthritis is one of the most painful rheumatic diseases and its incidence increases promptly with advancing age. In 75% of the patients, gouty arthritis initially strikes a single joint which is most commonly the big toe. In women gout develop in increasing numbers after menopause eventually at an incidence rate equal to that of men (Hootman and Helmick 2006). In elderly patients, an occurrence of gout is usually less spectacular than in middle age and often implies an upper extremity poly or mono articular presentation rather than the classic mono articular lower extremity picture commonly displayed by middle-aged men. In older patients, gout can be more likely the clinical picture of osteoarthritis or rheumatoid arthritis (Cassetta and Gorevic 2004). Gouty arthritis can be classified into four stages depending upon level of severity namely; (i) Asymptomatic Hyperuricemia: In this stage, a person has elevated blood uric acid levels but no other symptoms and therefore requires no treatment. (ii) Acute Gouty Arthritis: In this stage, hyperuricemia leads to deposition of uric acid crystals in joint spaces, leading to gouty attacks (iii) Interval / Intercritical: This is the stage between acute gouty attacks with no symptoms and (iv) Chronic Tophaceous Gout: where the disease leads to permanent damage (Bhansing et al. 2010). Pathogenesis of gouty arthritis is critically influenced by sodium urate crystals and inflammatory processes they induce (Wise and Agudelo 1996). An inefficient renal urate excretion which leads to the elevated levels of uric acid above the saturation point for urate crystal formation is a major determinant of the disease. Purine catabolism leads to the formation of metabolic by-product, uric acid. In most mammals like higher primates, many birds and some reptiles, the urate oxidase (uricase) enzyme converts uric acid (relatively insoluble) to allantoin (highly soluble), leading to very low serum uric acid levels. A series of parallel mutations in the genes of uricase in the Miocene period results in the production of the dysfunctional form of uricase that leads to accumulation of relatively higher level of insoluble uric acid and subsequently the development of gouty arthritis (Liote and Ea 2006; Eggebeen 2007). Degradation of purines results in the endogenous production of uric aci d that usually contributes about two-thirds of the body urate pool, the remainder being originated by dietry intake. Of the uric acid formed daily, about 70% is excreted through the kidney while the rest is eliminated into the biliary tract and then converted to allantoin by colonic bacterial uricase. Therefore, in the vast majority gouty patients, hyperuricaemia occurs from reduced efficiency of renal urate clearance (Laubscher et al. 2009; Terkeltaub 2010). Development of the acute and chronic inflammatory gout is facilitated with the deposition of monosodium urate (MSU) crystals in joints. while MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a danger signal released from dying cells, little is known about the molecular mechanisms underlying MSU-induced inflammation (Martinon et al. 2006). For crystal formation n occurrence of gout, the ionic product of sodium and uric acid must be at or above the saturation level at which MSU crystals can form. Uric acid is a weak acid of pKa 5.75 and, it exists mainly in the ionized form as urate at physiological pH of 7.40. MSU has limited solubility under physiological conditions and the saturation level in plasma at a pH of 7.40 is 6.8 mg/dl (408 ÂÂ µmol/l) and when the plasma concentration exceeds this level, crystals may form in the joints and tissues (Terkeltaub 2010). MSU crystals preferentially form within cartilage and fibrous tissues, where they are relatively safer from contact with inflammatory mediators and may dwell for years without causing any defects. However, if shed from these sites of origin into the joint space or bursa, they are highly phlogistic particles that are immediately phagocytosed by monocytes and macrophages, stimulating the NALP3 inflammasome, triggering the release of IL-1 and other cytokines and a subsequent infiltration of neutrophils. Here the white cells release a package of inflammatory mediator substances which, in addition to destroying the crystals, also damage the surrounding tissues (Martinon et al. 2006). This acute inflammation defines the symptoms of an acute flare such as pain, swelling and redness and is typically self-limiting. Continual deposition of large numbers of MSU crystals may also heading out the joint damage through mechanical effects on cartilage and bone (pressure erosion), and probably low-gr ade inflammation. However, these more chronic crystal-tissue interactions still remain elusive and in need of further investigations (VanItallie 2010). Systematic Lupus Erythematosus (SLE) Introduction Lupus is an autoimmune disease which leads to both acute and chronic inflammation of various tissues of the human body. Lupus can be classified into different form depending upon the target tissues and organ system. Defined as Type III hypersensitivity reaction, people with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas such as heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. When internal organs are involved, the condition is referred to as systemic lupus erythematosus (SLE). The disease may be mild or severe and life-threatening (Wallace 2010). The prevalence of lupus ranges from approximately 40 cases per 100,000 persons among Northern Europeans to more than 200 per 100,000 persons among blacks (Johnson et al. 1995). In the United States, the number of patients with lupus exceeds 250,000. The life expectancy of such patients has improved from an approximate 4-year survival rate of 50% in the 1950s to a 15-year survival rate of 80% today (Merrell and Shulman 1955; Abu-Shakra et al. 1995). Even so, a patient in whom lupus is diagnosed at 20 years of age still has a 1 in 6 chance of dying by 35 years of age, most often from lupus or infection. Later, myocardial infarction and stroke become important causes of death (Cervera et al. 2003). Anatomy and Pathophysiology SLE is an inflammatory and multi-systemic autoimmune disorder characterized by an uncontrolled auto-reactivity of B and T lymphocytes. This results in the production of auto antibodies (auto-Abs) against self-directed antigens and causes tissue destruction (Cuchacovich and Gedalia 2009). Pathogenesis of SLE is a multi-factorial event and the exact mechanism of disease development and progression is still unclear. Multiple factors are known to be associated with the development of the disease such as genetic, racial, hormonal, and environmental factors. Defects in apoptosis are one of the proposed mechanisms involved in patho-physiological events of SLE. Imbalance in apoptotic machinery leads to the production of auto-antibodies. These antibodies lack the ability to differentiate between pathogenic and normal host cells and cause increase cell death and abnormalities in immune tolerance (Andrade et al. 2000; Rahman and Isenberg 2008). It is believed that all the major components of immune system are involved in SLE progression at various levels. Mostly proteins present in cell nucleus are targeted by the immune system. The likely environmental triggers for SLE include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. It is observed that in patients suffering from SLE, there is increased cell death in monocytes and keratinocytes and hyper expression of Fas protein by B and T cells of the immune system. Tingibl e body macrophages (TBMs) are large phagocytic cells present in the germinal centers of secondary lymph nodes. They express CD68 protein. These cells normally engulf B cells which have undergone apoptosis after somatic hypermutation. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells (Gaipl et al. 2006). Monocytes isolated from whole blood of SLE sufferers show reduced expression of CD44 surface molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBM), which are found in the germinal centres of lymph nodes, even show a definitely different morphology; they are smaller or scarce and die earlier. Serum components like complement factors, CRP, and some glycoproteins are, furthermore, decisively important for an efficiently operating phagocytosis. With SLE, these components are often missing, diminished, or inefficient. References Abu-Shakra M, Urowitz MB, Gladman DD, Gough J (1995) Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality. J Rheumatol 22:1265-1270 Andrade F, Casciola-Rosen L, Rosen A (2000) Apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 26:215-227, v Bhansing KJ, van Bon L, Janssen M, Radstake TR (2010) Gout: a clinical syndrome illustrated and discussed. Neth J Med 68:352-359 Cassetta M, Gorevic PD (2004) Crystal arthritis. Gout and pseudogout in the geriatric patient. Geriatrics 59:25-30; quiz 31 Cervera R et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82:299-308 doi: 10.1097/01.md.0000091181.93122.55 Cuchacovich R, Gedalia A (2009) Pathophysiology and clinical spectrum of infections in systemic lupus erythematosus. Rheum Dis Clin North Am 35:75-93 doi: S0889-857X(09)00004-0 [pii] 10.1016/j.rdc.2009.03.003 Eggebeen AT (2007) Gout: an update. Am Fam Physician 76:801-808 Gaipl US et al. (2006) Clearance of apoptotic cells in human SLE. Curr Dir Autoimmun 9:173-187 doi: 10.1159/000090781 [pii]Â   10.1159/000090781 Hootman JM, Helmick CG (2006) Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum 54:226-229 doi: 10.1002/art.21562 Johnson AE, Gordon C, Palmer RG, Bacon PA (1995) The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum 38:551-558 Laubscher T, Dumont Z, Regier L, Jensen B (2009) Taking the stress out of managing gout. Can Fam Physician 55:1209-1212 doi: 55/12/1209 [pii] Liote F, Ea HK (2006) Gout: update on some pathogenic and clinical aspects. Rheum Dis Clin North Am 32:295-311, vi doi: S0889-857X(06)00024-X [pii] 10.1016/j.rdc.2006.03.001 Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237-241 doi: nature04516 [pii] 10.1038/nature04516 Merrell M, Shulman LE (1955) Determination of prognosis in chronic disease, illustrated by systemic lupus erythematosus. J Chronic Dis 1:12-32 Mikuls TR, Saag KG (2006) New insights into gout epidemiology. Curr Opin Rheumatol 18:199-203 doi: 10.1097/01.bor.0000209435.89720.7c 00002281-200603000-00014 [pii] Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929-939 doi: 358/9/929 [pii] 10.1056/NEJMra071297 Roddy E, Doherty M (2010) Gout. Epidemiology of gout. Arthritis Res Ther 12:223 doi: ar3199 [pii] 10.1186/ar3199 Roddy E, Zhang W, Doherty M (2007) The changing epidemiology of gout. Nat Clin Pract Rheumatol 3:443-449 doi: ncprheum0556 [pii] 10.1038/ncprheum0556 Shai A, Rimar D, Rozenbaum M, Wolfovitz E, Rosner I (2010) Gout in young migrant Filipino women in Israel: a changing epidemiology. Case reports and review of the literature. Rheumatol Int 30:1685-1687 doi: 10.1007/s00296-009-1198-7 Terkeltaub R (2010) Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 6:30-38 doi: nrrheum.2009.236 [pii] 10.1038/nrrheum.2009.236 Terkeltaub RA (2003) Gout. New England Journal of Medicine 349:1647-1655 doi: doi:10.1056/NEJMcp030733 VanItallie TB (2010) Gout: epitome of painful arthritis. Metabolism 59 Suppl 1:S32-36 doi: S0026-0495(10)00229-5 [pii] 10.1016/j.metabol.2010.07.009 Wallace DJ (2010) Advances in drug therapy for systemic lupus erythematosus. BMC Med 8:77 doi: 1741-7015-8-77 [pii] 10.1186/1741-7015-8-77 Wise CM, Agudelo CA (1996) Gouty arthritis and uric acid metabolism. Curr Opin Rheumatol 8:248-254

Openess Trade and Growth Essay -- Economic Development, Trade Liberali

The economic growth story is as long as the history of economic thought. Since the early classics like Adam Smith, David Ricardo and Thomas Malthus studied the issue of growth or introduced fundamental concepts such as diminishing returns and their relationship with the accumulation of physical or human capital, the relationship between technological progress and labor specialization or focus competitive analysis tool dynamic equilibrium. As part of these theories appears arises that relationship between trade openness and economic growth is positive. These theories between trade openness and economic growth can be located more than 200 years, with the mercantilist theories. Under these concepts, International trade benefited a nation only if the other was impaired. In 1776, Adam Smith broke with this theory stating that if two nations trade voluntarily with one another, both benefit. This is based on "absolute advantage." Later, David Ricardo (1817) said that while a nation was less efficient than another in production of both goods, it is still likely to trade in a mutually beneficial. This essay attempts to show what is the relationship between trade openness and economic growth and explain their implications for Paraguay. There are many conceptions about the relationship between economic growth and trade but all the authors implies that there is a beneficial situation. For example, Yuhong Li,, Zhongwen Chen, Xiaoyin Wang (2010) Conclude that In open economies, development of foreign trade greatly impacts on GDP growth. According Douglas K. Agbetsiafa â€Å"Openness of the economy to international trade promotes economic development and growth while growth itself brings about associated increase in openness to trade† (p.... ...ee of trade openness has been a topic of debate in the literature in recent years for its effect on the growth of countries. Some authors argue that trade openness is positive because to diversify the supply and provision of goods and services to a emergency. The other position assumes that trade liberalization does not imply any benefit as all internalize external shock quickly. Trade openness is related to the agricultural export structure and dependence on imported products. Paraguay has to make ever-increasing efforts to receive the same amount of income whereas the increase in the volume of exports was higher than the value. Much of the current discussion on the impact of trade on growth is relevant to Paraguay considering that there has been trade liberalization, but public policies are needed to support the development of related institutional factors.

Ex Memo Essay

Subject: Improvement on written refusals I am writing today to provide all employees with some useful tips on how to compose a customer refusal letter. While the example letter to Mr. Largo is factual, there are some things that could be presented much better. Presentation of facts could determine if we are able to retain customers and reflect the credibility of the company. Some key elements that I want to focus on are: †¢ Tone †¢ Punctuation and Grammar †¢ Professionalism The best way to begin a refusal is by setting an apologetic tone. You do not want to point blame at the customer, even if you feel they are wrong. Show empathy, and see if you can help them in anyway possible. Remember when writing a refusal all that’s representing our company are the words on the page; so we must use correct grammar and punctuation. Thank you for your attention and your time. I encourage our department to utilize these factors when writing a refusal letter. I want all refusals emailed to me, before mailing them. If there are any questions, problems or concerns you can reach me by email (twhitmore@mainappliance. com). MAIN STREET APPLIANCES 576 Main Street Gainesville, FL 33312 To: John Largo From: John Wright, Customer Relations Supervisor Date: July 20, 2009 Subject:$50 discount voucher Dear Mr. Largo, We apologize for not being able to grant your request for a replacement refrigerator. Main Street Appliances values you as a preferred customer, and would like to offer you a $50 discount voucher, to put towards a new refrigerator, with a 1year warranty. The voucher can only be used at the local Main Street location and expires on August 17, 2009. We apologize, again, for any inconvenience this issue may have caused. In the event that we may be of any further assistance, please call our customer service hotline (800-MAIN-STREET ext. 112) or by email (twhitmore@mainappliance. com). Sincerely, John Wright Customer Service

Essay on Susan Glaspells Trifles Men vs. Women - 872 Words

Susan Glaspell’s one-act play, Trifles, weaves a tale of an intriguing murder investigation to determine who did it. Mrs. Wright is suspected of strangling her husband to death. During the investigation the sheriff and squad of detectives are clueless and unable to find any evidence or motive to directly tie Mrs. Wright to the murder. They are baffled as to how he was strangled by a rope while they were supposedly asleep side by side. Glaspell artfully explores gender differences between men and women and the roles they each fulfill in society by focusing on their physicality, their methods of communication and vital to the plot of the play, their powers of observation. In simple terms, the play suggests that men tend to be assertive,†¦show more content†¦While each proses a serve of justice and determination to do the right thing; the men approach the crime scene emotionless, indifferent and determined to go in and get to the bottom of the mystery as quick as possib le, and push aside the little details. Little do they know that the things they are putting off could be very essential to their case? For example, in a conversation between the attorney and Mr. Hale who remarks, â€Å"..I said to Harry that I didn’t know as what his wife wanted made such a difference to John..† who was interrupted by the attorney in mid conversation and interjects, â€Å"Let’s talk about that later, Mr. Hale. I do want to talk about that, but tell now just what happened when you got to the house.† (1127) Meanwhile, while the men are out on their hunt for clues, the women stay in the kitchen to look through Mrs. Wright’s things and discuss a motive for why she killed her husband. Glaspell proposes a plan that by looking deeper into circumstances, you may in turn fully understand its true meaning; leaving no stone left unturned. Glaspells suggests that men tend to assume that nothing of importance occurs in the kitchen, where the wo men are at work, and this can be related to their negative attitudes towards women. For example, the attorney says, â€Å"I guess well go upstairs first and then out to the barn and around there. Youre convinced that there was nothing important here nothing that would point to anyShow MoreRelatedSusan Glaspell’s One-Act Play, Trifles: Men Vs Women1190 Words   |  5 Pagesliterature is Susan Glaspell’s one-act play â€Å"Trifles.† Some see it as an example of early feminist drama, others the idea of the way small towns deal with issues like murder, still others the gender differences in both the interpretation and analysis of facts surrounding a mysterious crime. In general, the play is based on the murder of a Mr. Wright, and the title of the play comes from the critique from the men of the town, who berate the women for spending time â€Å"worrying over trifles† (Glaspell 918)Read MoreCritical Analysis Of Trifles By Susan Glaspell1016 Words   |  5 PagesPerspective: Readers Response Criticism to â€Å"Trifles† by Susan Glaspell The play written by Susan Glaspell in 1916 is based on the murder of John Wright where the prime suspect is his spouse; Minnie Foster. â€Å"Trifles† is fixated on the investigation of the social division realized by the strict gender roles that enable the two men and women to have contending points of view on practically every issue. This is found in the way the men view the kitchen as they consider it as not having anything of significantRead MoreSusan Glaspell s Trifles : Gender Differences And Stereotyping Explored2016 Words   |  9 PagesSusan Glaspell’s Trifles: Gender Differences and Stereotyping Explored Susan Glaspell’s Trifles is a dramatic play with satirical content that points out gender differences and how stereotyping affects perceptions of duty, justice, and law. Glaspell wrote Trifles in 1916, a time in America where women were consistently expected to be housewives and nothing more. Women’s limitations were clearly a spark of inspiration and reason for Glaspell to write Trifles, criticizing society with feministic intelligence