Foods That Reduce Inflammation

Reduce Inflammation

This eBook from professional trainer and nutritionist Thomas DeLauer and Dr. Mike Brookins shows you all of the secrets to reducing inflammation all through your body. These body hacks are secrets to the way that your body works that you would never have thought of. You will learn the foods that you will need to avoid in order to have a really healthy life. You will learn to reset your body in 7 days or less just by eating organic, really healthy foods. Food affects they way that your body works so much more than people tend to believe. You will learn how to cut through all the nonsense that you will read on the internet and get right to the part that heals your inflammation and other health problems. Inflammation is only a symptom If you are not healthy and eating well, your whole body will suffer. We give you a way to reverse that! Read more...

Organic Health Protocol Overview

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Whats Wrong with Anti Inflammatory Drugs

Should Nonsteroidal Anti-Inflammatory Drugs Be Used to Treat Osteoarthritis Rheumatic Diseases Clinics of North America 19 (1993) 29-44. Shield, M. J. Anti-Inflammatory Drugs and Their Effects on Cartilage Synthesis and Renal Function. European Journal of Rheumatology & Inflammation, 13 (1993) 7-16. Simon, L. S., et al. Anti-Inflammatory and Upper Gastrointestinal Effects of Celecoxib in Rheumatoid Arthritis A Randomized Controlled Trial. JAMA 282 (1999) 1921-1928. Wolfe, M. M., D. R. Lichtenstein, and G. Singh. Gastrointestinal Toxicity of Nonsteroidal Anti-Inflammatory Drugs. New England Journal of Medicine 340 (1999) 1888-1899.

Antiinflammatory mediators

Anti-inflammatory mediators have been identified - IL-4, IL-10, IL-11, IL-13, transforming growth factor-b, TNF receptors and receptor antagonist to IL-1 - the actions of which are opposed to those of the proinflammatory mediators. Unfortunately, their activities and role in sepsis remain unclear as the plasma concentration of some such as the soluble TNF receptors are also elevated in many disease entities not related to sepsis, for example rheumatoid arthritis and systemic lupus, as well as in normal pregnancy. A balance is required between pro-inflammatory and anti-inflammatory mediators to maintain homeostasis and facilitate recovery of the patient. If either response offsets the other, then SIRS with MODS and anergy with infection may occur. In addition to these anti-inflammatory mediators, studies have shown a reduction in antibody production, lack of delayed hypersensitivity and depression of lymphocyte activation following trauma and in the critically ill. This anergy may...

Anti Inflammatory Therapy in the Presence of Active Ulcers

As a general rule, one should substitute non-NSAID analgesics for NSAIDs in the presence of active ulcers. Most NSAID ulcers will heal spontaneously after stopping NSAID therapy but healing is accelerated with antisecretory drug therapy. NSAID ulcers will heal with standard doses of PPIs despite continued NSAID use but the time to complete healing may be prolonged. Thus, patients with active ulcers who cannot discontinue anti-inflammatory therapy should receive the least ulcerogenic NSAID at the lowest effective dose plus cotherapy with a gastroprotective agent, preferably a PPI.

Nonsteroidal Anti Inflammatory Drug Enteropathy

Nonsteroidal antiinflammatory drugs (NSAIDs) cause small bowel inflammation in 50 to 70 of patients on long term conventional NSAIDs. The patients with the enteropa-thy consequentially bleed from the small bowel (2 to 10 mL d) and lose protein (Bjarnason et al, 1992). The bleeding is not by itself sufficiently severe to cause iron deficiency. However if there concomitant overt bleeding (heavy periods), reduced food intake, hypochlorhydria (primary or secondary to acid lowering drugs), and malabsorption of iron, then the small intestinal bleeding does become an important contributing factor to the IDA, which is very common in patients with rheumatoid arthritis. Patients with NSAID-induced enteropathy also lose protein from the inflammatory site. Similar to the blood loss, this only becomes clinically evident in a few patients, because the liver has substantial reserve capacity to produce albumin. Nevertheless about 10 of patients with rheumatoid arthritis who are sufficiently unwell as...

Nepafenac Antiinflammatory [5255

Nepafenac, launched last year by Alcon Laboratories, is a topical ophthalmic medication indicated for the treatment of ocular pain and inflammation associated with cataract surgery. Nepafenac is a prodrug of amfenac, which is an NSAID and a potent non-selective inhibitor of COX-1 (IC50 0.25 mM)) and COX-2 (IC50 0.15 mM). Nepefenac itself exhibits only weak activity against COX-1 (IC50 64.3 mM). Amfenac (Fenazox) has been marketed in Japan since 1986 for the treatment of rheumatoid arthritis, post-surgical pain, and inflammation. With most NSAIDs that are currently being used as topical ophthalmic agents, the maximum drug concentration is achieved on the ocular surface, with progressively lower concentrations in the cornea, aqueous humor, vitreous, and retina. Ne-pafenac has been found to have a penetration coefficient that is 4 - 28 times greater than that achieved with conventional NSAIDs such as diclofenac, bromofenac, and ketorolac. In addition, the bioconversion of nepefenac to...

Nonsteroidal Antiinflammatory Drugs

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Naproxen sodium Action Kinetics The antiinflammatory effect is believed to result from the inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. The agents are effective in reducing joint swelling, pain, and morning stiffness, as well as in increasing mobility in individuals with inflammatory disease. They do not alter the course of the disease, however. Their anti-inflammatory activity is comparable to that of aspirin. The analgesic activity is due, in part, to relief of inflammation. Also, the drugs may inhibit lipoxygenase, inhibit synthesis of leuko-trienes, inhibit release of lysosomal enzymes, and inhibit neutrophil aggregation. Rheumatoid factor production may also be inhibited. The antipyretic action occurs by decreasing prostaglandin synthesis in the hypothalamus, resulting in an increase in peripheral blood flow and heat loss as well as promoting sweating. NSAIDs also inhibit miosis induced by...

Nonsteroidal Antiinflammatory Antirheumatic Agents

Anti Inflammatory Antirheumatic Action

At relatively high dosage (> 4 g d), ASA (p. 198) may exert antiinflammatory effects in rheumatic diseases (e.g., rheumatoid arthritis). In this dose range, central nervous signs of overdosage may occur, such as tinnitus, vertigo, drowsiness, etc. The search for better tolerated drugs led to the family of non-steroidal antiinflammatory drugs (NSAIDs). Today, more than 30 substances are available, all of them sharing the organic acid nature of ASA. Structurally, they can be grouped into carbonic acids (e.g., diclofenac, ibuprofen, na-proxene, indomethacin p. 320 ) or enolic acids (e.g., azapropazone, piroxi-cam, as well as the long-known but poorly tolerated phenylbutazone). Like ASA, these substances have analgesic, antipyretic, and antiinflammatory activity. In contrast to ASA, they inhibit cy-clooxygenase in a reversible manner. Moreover, they are not suitable as inhibitors of platelet aggregation. Since their desired effects are similar, the choice between NSAIDs is dictated by...

Antiinflammatory Activity

Celery has been found to have anti-inflammatory activity, with suppression of carrageenan-induced paw oedema observed in rats (Al-Hindawi et al 1989). Several constituents show anti-inflammatory activity, such as apigenin, eugenol, ferulic acid, luteolin and bergapton (Duke 2003). Studies in rats suggest that some celery seed extracts are highly effective in suppressing experimental arthritis without exhibiting any gastrotoxicity (Whitehouse et al 1999). Further in vivo studies suggest that celery seed extracts were gastroprotective for NSAID gastropathy and that this effect is mediated through non-prostaglandin mechanisms (Whitehouse et al 2001).

Harpagophytum procumbens Traditional Antiinflammatory Herbal Drug with Broad Therapeutic Potential

Abstract Harpagophytumprocumbens (Devil's Claw) is a traditional African herbal drug used by the natives of the Kalahari and Savannah desert regions to treat a variety of ailments. In Europe, the anti-inflammatory properties of Harpagophytum procumbens extracts (Hp) have been the basis for its popular use in the treatment of inflammatory disorders of the musculoskeletal system and of low back pain. This is the subject of a draft monograph recently issued by the European drug authorities (EMEA). There is good clinical evidence for Hp's use in treating painful osteoarthri-tis, but more evidence (such as from phase-III trials) is needed before Hp can be considered a standard treatment of osteoarthritis and other chronic inflammatory diseases. Here, the published evidence is reviewed that reveal the anti-inflammatory effects of Hp including inhibition of key mediators and promoters of inflammation. The relevance of these effects for the therapeutic use of Hp in osteoarthritis is...

Nonsteroidal antiinflammatory drugs NSAIDs

A class of drugs that is anti-inflammatory and analgesic. Although NSAIDs effectively reduce pain and inflammation, they do not affect the overall outcome or progression of arthritis. Therefore, to treat rheumatoid arthritis, NSAIDs are often combined with disease-modifying drugs (DMARDs). NSAIDs inhibit cyclooxygenase (COX) enzymes and thus decrease the production of prostaglandins. There are two COX enzymes, COX-1 and COX-2, that differ in their function. COX-1 is found in many tissues at a low level of activity and has important effects in promoting platelet aggregation and protecting against peptic ulcers. COX-2 is often present only in cells that have been stimulated, a process known as induction. COX-2 is induced in response to inflammation. Drugs that inhibit COX-2 decrease the formation of prostaglandins in cells where their production has been stimulated and are therefore anti-inflammatory. Drugs that inhibit COX-1 have two important effects. First, they decrease the...

Anti Inflammatory Effects

Organic and aqueous feverfew powdered leaf extracts were found to inhibit IL-1-induced prostaglandin E2 release from synovial cells, IL-2-induced thymidine uptake by lymphoblasts, and mitogen-induced uptake of thymidine by peripheral blood mononuclear cells (PBMCs) (23). Parthenolide also inhibited thymidine uptake by PBMCs. Both parthenolide and the extracts were cytotoxic to the PBMCs and synovial cells thus, the anti-inflammatory effects of feverfew may be secondary to cytotoxicity. These results reflect those of previous researchers who found parthenolide and other sesquiter-pene lactones to be cytotoxic to cultures of human fibroblasts, human laryngeal carcinoma cells, and human cells transformed with simian virus 40 (24). The anti-inflammatory effect of dried powdered feverfew leaf was compared to placebo in the treatment of rheumatoid arthritis (RA) (25). This double-blind, randomized study used dried powdered feverfew leaf 70-86 mg (mean 76 mg), equivalent to 2-3 mol of...

The Steroidal Antiinflammatory Agents

Anti-inflammatory action of one of these, cortisone, revolutionalized the treatment of rheumatoid arthritis. This stimulated a great deal of research in the 1950s and 1960s leading to useful steroidal anti-inflammatory agents. Steroid therapy can produce significant improvements in many inflammatory diseases but there can be adverse side effects. The mineral-corticoid activity of these compounds can lead to water retention. Hence, there have been structural variations to increase the gluco-corticoid anti-inflammatory activity and to diminish the mineral-corticoid activity and thus to reduce the amount of steroid required for treatment. Prednisolone 5.74 is the most widely used steroid for the treatment of inflammatory and allergic diseases. Betamethasone 5.75, dexamethasone 5.76, triamcinolone 5.77 and synalar 5.78 are other examples. Where it is necessary to transport the drug across fat barriers, for example, in topical creams that are used to treat local inflammation, the steroid...

Anti Inflammatory Activity

The antiinflammatory effects of ginger oil on arthritic rats were studied (29). A 0.05-mL suspension of heat-killed Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg mL) was injected into the knees and paws to induce arthritis in treatment rats. Rats were randomized to receive 33 mg kg of ingwerol (ginger oil obtained by steam distillation of dried ginger root), 33 mg kg of eugenol (a component of clove oil purported to have antiinflam-matory activity), or normal saline orally for 26 days, beginning just prior to the induction of arthritis. Compared to normal saline, both treatments were effective in decreasing both knee and paw swelling.

Anti Inflammatory Agents

Bromelain's primary active component is a sulfhydryl proteolytic fraction, but bromelain preparations also contain nonproteolytical enzymes, several protease inhibitors, activators, and organically bound calcium 191 . Bromelain has been demonstrated to have both direct and indirect actions involving other enzyme systems in exerting its anti-inflammatory effect. It has also been shown to remove T-cell CD44 molecules from lymphocytes, thereby affecting T-cell activation and leading to a reduction of inflammation. Bromelain and pred-nisone have been shown to be comparable in their ability to reduce inflammation in rats 193,197 . Bromelain has been used as an anti-inflammatory and analgesic agent in treating the symptoms of arthritis 198 . Serratiopeptidase is another enzyme preparation used as an anti-inflammatory agent. The enzyme is derived from bacteria belonging to genus Serratia. It helps eliminate inflammatory swelling, accelerates liquefaction of pus, and enhances the action of...

Heat Shock Proteins Are Targets For T Cell Regulation How Microbial Hsp Induce Il10 Producing Antiinflammatory T Cells

Abstract Mechanisms of anti-inflammatory T cell regulation are studied very actively, especially since the (re-)discovery of T cell subpopulations with specialized regulatory activities. This is expected to lead to the development of novel immunotherapeutic approaches, especially in chronic autoimmune diseases. HSP are possible targets for regulatory T cells due to their enhanced expression in inflamed (stressed) tissues and the collected evidence that HSP immunizations induced anti-inflammatory immunoregulatory T cell responses. First evidence for an immuno-regulatory role of heat shock proteins (HSP) in autoimmunity was obtained through the analysis of T cell responses in the rat model of adjuvant arthritis and the findings that HSP immunisations protected against the induction of various forms of autoimmune arthritis in rat and mouse models. Since then, immune reactivity to HSP was found to result from inflammation in various disease models and in a variety of human inflammatory...

Screening experiments for antiinflammatory properties

Antiinflammatory Foods

This chapter describes some examples of screening experiments aimed at identifying antiinflammatory constituents of plants. A large number of plants and herbs are known for their anti-inflammatory properties. Well-known examples are willow bark (contains salicin, from which aspirin is derived), Boswellia serrata (boswellic acids) and turmeric (curcumin). In addition to these, many other herbs have been suggested to be anti-inflammatory. Inflammation plays a role in many different clinical disorders. In addition to the obvious inflammatory diseases such as arthritis, asthma, Crohn's disease, psoriasis and so on, inflammation also plays an important role in diseases such as atherosclerosis, diabetes, Alzheimer's and many other diseases. In many of these, a disordered immune system contributes to the onset and or progression of the disease. What are important targets for anti-inflammatory therapies A key regulatory factor in the inflammatory response is the transcription factor family...

Antiinflammatory Effects of Chondroitin Sulfate

Mediators, which include prostaglandins. Therefore, part of the anti-inflammatory activity of ChS could be due to its effect on prostaglandin production. ChS-A decreased matrix proteoglycan loss and erosion in a mouse model of collagen-induced arthritis 14 . This is again attributed to a decrease in NF-kB nuclear translocation and decreased degradation of IKB-a protein, which leads to decreased expression of proinflammatory molecules. A decrease in MMP-13 expression and synthesis, lipid peroxidation and neutrophil activation is also seen in the presence of ChS. Finally, endogenous antioxidant levels increased with ChS treatment. Together, these anti-inflammatory responses in the presence of ChS contribute to the observed decrease in the degradation of cartilage tissue.

Lumiracoxib Antiinflammatory [4851

As a second-generation, selective cyclooxygenase (COX-2) inhibitor, lumiracoxib is devoid of the gastrointestinal issues that plague other non-selective, non-steroidal, anti-inflammatory drugs (NSAIDs) that crossover to COX-1. As an inhibitor of the inducible COX-2 that is up-regulated in pathological processes of pain and inflammation, lumiracoxib blocks the conversion of arachidonic acid to prostaglandins, the mediators of the pathological effects. It's mode of binding to COX-2 has been found to differ from the other selective COX-2 inhibitors the carboxylic acid forms hydrogen bonds with Tyr-385 and Ser-530 in the catalytic site rather than seeking interactions within the larger hydrophobic side pocket. In human whole blood, lumiracoxib displays an IC50 value of 0.13 mM for COX-2 versus 67 mM for COX-1, resulting in a selectivity ratio of 515. Regarding its synthesis, lumiracoxib may be prepared by a couple of routes. While the construction of the diarylamine core via a...

Antiinflammatory And Analgesic

The anti-inflammatory effects of ginger may be due to its effects on the arachidonic acid cascade, as COX-1 and -2 and lipoxygenase inhibition has been shown in vitro (Kobayashi et al 1987) and high oral doses of an aqueous extract of ginger (500 mg kg) significantly lowered serum PGE2 and thromboxane B2 levels in rats (Thomson etal 2002). No one single constituent seems to be responsible for the anti-inflammatory effect of ginger. An acetone extract containing gingerols, shogaols and minor compounds like gingerenone A, 6 -gingerdiol, hexahydrocurcumin and zingerone have been shown synergistically to produce dose-dependent anti-inflammatory effects (Schuhbaum & Franz 2000). Other studies have identified the gingerols and diarylheptanoids and gingerdione as the key compounds responsible (Flynn et al 1986, Kiuchi et al 1992). Gingerol and 8-gingerol have been found to evoke capsaicin-like intracellular Ca2 + transients and ion currents in vitro and it has been suggested that...

In Vivo Anti Inflammatory Effects of Hp Extracts and Harpagoside

Most of the standard anti-inflammatory in vivo models depend on chemically induced tissue damage and measurement of the inflammatory response in oedema. In the rat model of formalin-induced arthritis, parenteral administration of an aqueous extract of Hp (20 mg kg) was as effective as the non-steroidal anti-inflammatory drug (NSAID) phenylbutazone, but harpagoside was ineffective 17 . In Freund's adjuvant model of arthritis, again in rat, injections of an ethanolic extract of Hp, at 25, 50 and 100 mg kg, was demonstrated to exert a significant analgesic and anti-inflammatory (anti-oedematous) effect following both acute and chronic treatment (20 days) 18 . A number of studies reported significant anti-inflammatory effects in the carageenan-induced rodent oedema model following parenteral administration of an aqueous ethanolic (60 ) extract 19 , of an aqueous extract 20, 21 and of a non-characterised extract 22 . However, in the same model, oral administration of various extract forms...

Antiinflammatory effects

Chronic inflammation is a pathophysiological condition of the body associated with various disorders such as arthritis, neurodegenerative diseases, cancer, diabetes, and cardio vascular disease. Scientists are in search of natural anti-inflammatory agents and phlorotannins have also getting much attention due to the shown promising anti-inflammatory potential. Ryu et al. (2009) have shown anti-inflammatory effects of dieckol and as therapeutics to treat arthritis. Both phlorotannins have suppressed the unregulated expression of cyclooxy-genase-2 (COX-2), inducible nitric oxide (iNOS), MMP 1,3,13 in activated human osteosarcoma cells (MG63). Phloroglucinol, the monomer unit, has also exerted significant anti-inflammatory activity by inhibiting inflammatory mediators (tumor necrosis factor a, Interleukin 1 p, interleu-kin 6, nitric oxide, and prostaglandin E2) in lipopolysaccharide-stimu-lated RAW264.7 cells (Kim and Kim, 2010). Overactivation of microglial cells is leading to chronic...

Antiinflammatory Drug Trials In Ad Future Directions

Toxicity remains a major roadblock to a study of antiinflammatory dosage of a traditional NSAID. One way to reduce NSAID toxicity is to add a cytoprotective agent to the treatment regimen. Misoprostol is a synthetic prostaglandin known to reduce the incidence of NSAID gastropathy. However, a recent report of a trial of diclofenac plus misoprostol in AD patients indicated that this combination was not tolerated any better than indomethacin the drop-out rate in this 25 week trial was 50 in the active drug group, rendering the results of the study inconclusive (Scharf et al., 1999). It is unlikely that a study of a treatment regimen that is tolerated (over the course of a year) by a minority of subjects will yield definitive results. The ADCS has opted to study two NSAID-type regimens that are expected to have substantially less toxicity than the indomethacin and diclofenac regimens reported. The first is the new selective COX-2 inhibitor rofecoxib. As discussed above, COX-2 may be the...

The Contrasting Pro and Anti Inflammatory Effects of IL10 in Different Pathologic Conditions

Several animal models of disease describe either pro or anti-inflammatory activity of IL-10. IL-10 knockout mice develop chronic inflammatory bowel disease3 In transgenic models, IL-10 reduces the ability of mice to mount significant T or B cell responses to ovalbumin, Listeria monocytogenes and Leishmania and prevents experimental autoimmune encephalomyelitis.4 In addition, treatment with IL-10 can reduce inflammation in experimental autoimmune en-cephalomyelitis, pancreatitis, diabetes mellitus, endotoxemia and arthritis.1

Protective Mechanisms Related to the Antiinflammatory Properties of NSAIDs

Inhibition of local prostaglandin synthesis and inflammation clearly underlie the analgesic effects of NSAIDs in rheumatoid arthritis (Simmons et al. Warner & Mitchell, 2004). However, whether the anti-inflammatory effects of NSAIDs in AD predominantly results from COX inhibition and reduced synthesis of proinflammatory prostanoids remains uncertain. Reduced generation of inflammatory prostaglandins has been shown in brain of rats and Tg2576 mice after peripheral administration of NSAIDs (Abdel-Halim, Sjoquist, & Anggard, 1978 Quinn et al., 2003 Sung et al., 2004) indicating central efficacy in these animal models. Data about CNS penetration of NSAIDs in humans is limited, but published cerebrospinal fluid (CSF) concentrations indicate the drug levels are sufficient for inhibition of COX activity in brain (Dembo, Park, & Kharasch, 2005 Gasparini, Ongini et al., 2004). Primary cell culture experiments have shown that proinflammatory cytokines like IL-1 and TNF-a can upregulate...

Antiinflammatory Aspects of n3 Fatty Acids

Many experimental studies have provided evidence that incorporation of alternative fatty acids into tissues may modify inflammatory and immune reactions and that n-3 fatty acids in particular are potent therapeutic agents for inflammatory diseases. Supplementing the diet with n-3 fatty acids (3.2 g EPA and 2.2 g DHA) in normal subjects increased the EPA content in neutrophils and mono-cytes more than sevenfold without changing the quantities of AA and DHA. The anti-inflammatory effects of fish oils are partly mediated by inhibiting the 5-lipoxygenase pathway in neutrophils and monocytes and inhibiting the leukotriene B4 (LTB4)-mediated function of LTB5 (Figure 5). Studies show that n-3 fatty acids influence interleukin metabolism by decreasing IL-1,3 and IL-6. Inflammation plays an important role in both the initiation of atherosclerosis and the development of athero-thrombotic events. An early step in the atherosclerotic process is the adhesion of monocytes to endothelial cells....

Antiinflammatory

Chamomile extract and various isolated constituents within chamomile have demonstrated anti-inflammatory activity in a variety of tests. Chamomile extract showed anti-inflammatory effects when applied topically in animal models of inflammation (Al-Hindawi et al 1989, Plevova 1999, Shipochliev et al 1981). In a comparative trial, hydro-alcoholic extracts of chamomile produced antiinflammatory actions when applied topically in the croton ear test in the mouse. The hydro-alcoholic extract reduced oedema in a dose-dependent manner and was equivalent in effectiveness to benzydamine at twice the usual clinical dose, but hydrocortisone was found to be the most effective treatment (Tubaro et al 1984). Another comparative study investigated the anti-inflammatory effects of an extract prepared from dried flowers, an extract based on fresh flowers, and the volatile oil, in croton oil-induced dermatitis of mouse ear. The activity of fresh chamomile equalled the activity of the reference drug...

Name Of The Medicinal Product

Known hypersensitivity to nimesulide or to any of the excipients of the products. History of hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) in response to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. History of hepatotoxic reactions to nimesulide. Non-steroidal anti-inflammatory drugs have been reported to reduce the clearance of lithium, resulting in elevated plasma levels and lithium toxicity. If Nimesulide containing medicinal products are prescribed for a patient receiving lithium therapy, lithium levels should be monitored closely.

Actions on joint destruction in arthritis

Much interest has been shown in the past 2-3 decades on the actions of NSAIDs on joint destructive processes in arthritic diseases, especially in OA and RA 298311 . The issue has been debated whether or not NSAIDs should be used in the treatment of OA because of claims that some of these drugs may accelerate cartilage or bone destruction in this condition 300, 302, 308 . Some have proposed that it is only pain relief that is needed in the treatment of osteoarthritis and not control of inflammation that paracetamol and other analgesics (including weak opioids) should be employed at least as first-line agents since these give adequate pain relief without having the risk of joint destructive changes thought to occur with some NSAIDs 300, 302-306, 308, 311 (see also Chapter 5). The situation is complicated because (a) analgesic activity which is provided by all these drugs, distinct from anti-inflammatory effects per se of the NSAIDs, may contribute to over-use of already degrading joints...

H3co2s

Qlechoma brevituba Kuprian. is a stoloniferous, perennial, prostrate herb that grows in China. The leaves are simple, decussate and exstipulate. The petioles are long. The base of the blade is cordate. The flowers are tubular, dilated at apex, and bilobed. The fruits are dark brown, oblong-ovoid, smooth or impressed-punctuate, and glabrous. The plant is used in China to reduce fever, promote urination and the heart tone, and to cure colds and gravel. The pharmacological potential of Glechoma brevituba Kuprian. remains unexplored. An interesting feature of the Glechoma species is their ability to elaborate long-chain unsaturated fatty acids with anti-inflammatory, analgesic, antipyretic potentials. One such fatty acid is acid, an antagonist of PGs E1 and D2 (27,28). Note also the the presence in the Glechoma species of a very unusual series of alkaloids (29), the structural features of which has some similarity to rofecoxib. Therefore, it would be interesting to learn whether these...

Dietary Treatments Optimal Nutrition

Maintaining healthy joints starts with adequate nutrition. Athletes should get adequate levels of protein to maintain and repair muscles, tendons, ligaments, and joints. Fruits and vegetables provide antioxidants that can help reduce inflammation and improve recovery from and adaptation to exercise. Essential fats, especially omega-3 fatty acids, are beneficial for promoting prostaglandins that control inflammation and pain pathways. Some essential fatty acids, such as omega-6 fatty acids, are easy to obtain from dietary sources because they are readily available in plant oils. A 1 1 or 2 1 ratio of omega-6 to omega-3 fats in the daily diet has been suggested. The amount of omega-3 fatty acids can be achieved by eating fish two to three times per week and using flax oil regularly. In animal studies, high levels of vitamin C (150 mg d) in the diet resulted in less severe joint damage in guinea pigs with surgically induced osteoarthritis compared with guinea pigs receiving low levels...

Use in sport and exercise

Much of the use in sport and exercise is based on the possibility that both glu-cosamine and chondroitin sulfate will be chondroprotective and will reduce inflammation and pain if injury occurs. People who exercise will use these supplements for varied reasons, and many use them more for prophylaxis than after an injury. There is a belief that these supplements will help avoid injury, will speed up healing if it occurs, and will be a useful adjunct if surgery has occurred.50

What Else Might Help

A variety of other nutrients, herbs, and habits also may reduce inflammation and pain associated with osteoarthritis. The least expensive change is to drink more water. According to Hugh D. Riordan, M.D., of the Center for the Improvement of Human Functioning International, Wichita, The herb ginger also may be helpful. A study in Arthritis & Rheumatism found that patients taking a ginger extract benefited from moderate improvements in knee pain. The study confirmed ginger's use as an anti-inflammatory agent in Chinese medicine, dating back more than twenty-five hundred years. Two topical treatments also can help. Several studies have found that creams containing capsaicin, the pungent component of hot peppers, can reduce the pain of osteoarthritis. Capsaicin blocks the transmission of pain chemicals to the brain. The effect appears to be strictly symptomatic, but other than a local sensation of heat, it is far safer than acetaminophen and other nonsteroidal anti-inflammatory drugs....

Vitamin E to Extinguish the Flames of Inflammation

Long known to reduce the risk of coronary artery (heart) disease, vitamin E has recently been shown, in scientific studies with people, to possess significant anti-inflammatory properties. More than any other single nutrient, vitamin E can significantly reduce a variety of key indicators and promoters of inflammation. For example, vitamin E lowers levels of C-reactive protein and interleukin-6 and reduces the activity of various types of adhesion molecules that promote inflammation throughout the body. In fact, vitamin E may be the single most important nutrient for lowering CRP levels. It should therefore not come as a surprise that, in addition to reducing the risk of heart disease, vitamin E is beneficial in Alzheimer's disease, arthritis, allergies, cancer, and many other inflammatory diseases. This chapter will focus on its emerging role as the premier anti-inflammatory vitamin.

Nutrients That Can Help

Many people benefit from the anti-inflammatory effect of omega-3 fish oils. However, it may take several months to see an improvement. A Scot Gamma-linolenic acid (GLA), an anti-inflammatory omega-6 fatty acid, may be even more effective in rheumatoid arthritis. GLA boosts levels of anti-inflammatory prostaglandin E1, which suppresses proinflammatory prostaglandin E2. Human trials with GLA (approximately 1.4 grams daily) have shown consistent benefits over several months, reducing symptoms by roughly one-third to one-half. Of course, results will vary from person to person, and a combination of supplements will likely have greater benefits.

Chronic inflammatory autoimmune diseases

Wall-induced arthritis (Volker et al., 2000) and reduced inflammation in rats with inflammatory bowel disease (Vilaseca et al., 1990). These improvements are associated with abolition of pro-inflammatory cytokine production and induction of anti-inflammatory cytokines in some models (Chandrasekar and Fernandes, 1994 Fernandes et al., 1994 Kleemann et al., 1998 Venkatraman and Chu, 1999). There have been a number of clinical trials assessing dietary supplementation with fish oils in several chronic inflammatory diseases in humans. N-3 PUFAs in the diet could affect the course of these diseases by altering the immune or inflammatory responses, thus modifying clinical symptoms. In some of the human trials of fish oil in inflammatory disease, anti-inflammatory effects of fish oil, including decreased production of circulating concentrations of pro-inflammatory mediators (LTB4, TNF-a, IL-1 and C-reactive protein), were observed. Many of the short-term placebo-controlled, double-blind...

Nelda Fish Oil to Relieve Pain

She figured there had to be an alternative, so she visited Hugh D. Riordan, M.D., president of the Center for the Improvement of Human Functioning International in Wichita, Kansas. Laboratory tests showed Nelda sensitive to some of her favorite foods, specifically dairy products and white potatoes, which she immediately stopped eating. She also began taking a number of anti-inflammatory supplements, including fish oils and antioxidant vitamins.

How to Buy and Use Fish Oil Supplements

Most fish oil supplements contain roughly three-fifths EPA and two-fifths DHA. If you want a high-EPA supplement use Omega-Brite, which contains 90 percent EPA and 10 percent DHA. To enhance the anti-inflammatory effects of omega-3 fish oils take gamma-linolenic acid supplements. (See the following section.) DHA supplements made from algae may not have the anti-inflammatory effect of EPA, but they may provide other health benefits, such as improving memory.

How to Buy and Use Olive

In this chapter you have read how good fats can help restore a normal inflammatory response and, in doing so, reduce symptoms of rheumatoid arthritis, osteoarthritis, and other inflammatory disorders. These fats also can lower blood pressure and lower your risk of heart disease and cancer. In the following chapter you will learn how vitamin E is now being recognized as the leading anti-inflammatory vitamin.

Functions and probable functions

One of the most characterized physiological functions of these polyunsaturated fatty acids is the role of eicosanoids. Eicosanoids work as autocrine paracrine hormones and mediate a variety of functions, such as immune response, blood pressure regulation, blood coagulation,33 movement of calcium and other substances into and out of cells, relaxation and contraction of muscles, and cell division and growth.34 The eicosanoids include substances such as prostaglandins and leukotrienes. Arachi-donic acid is the precursor for a group of eicosanoids that include series-2 prostaglandins and series-4 leukotrienes, while EPA is the precursor for a group of eicosanoids that include series-3 prostaglandins and series-5 leukotrienes.28 Eicosanoids derived from ro-6 fatty acids are pro-inflammatory and pro-aggregatory agonists, while those derived from ro-3 fatty acids tend to inhibit platelet aggregation and be anti-inflammatory.3536 Adequate production of the series-3 prostaglandins is thought...

Chondroitin Sulfate

A meta-analysis of chondroitin sulfate supplementation found 16 publications that fit criteria for inclusion. Criteria included types of joint involvement studied, study designs, numbers of patients enrolled, and pain index variables analyzed.27 It was concluded that chondroitin sulfate may be useful in osteoarthritis treatment however, results of the published studies were clouded by concomitant use of analgesics or NSAIDs, thus making conclusions about benefits difficult.27 Some have suggested that it can be used as an anti-inflammatory without dangerous effects on the stomach, platelets, and kidneys.28

Are there different kinds of omega fatty acids

National Library of medicine has this to say about omega 3 Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. The body cannot make these fatty acids on its own so omega-3s must be obtained from food. These different types of acids can be obtained in foods such as cold-water fish including tuna, salmon, and mackerel. Other important omega 3 fatty acids are found in dark green leafy vegetables, flaxseed oils, and certain vegetable oils. Omega-3 fatty acids have been found to be beneficial for the heart. Positive effects include anti-inflammatory and anti-blood clotting actions, lowering cholesterol and triglyceride levels, and reducing blood pressure. These fatty acids may also reduce the risks and symptoms for other disorders including diabetes, stroke, rheumatoid

Etiology and pathogenesis

Some published reports suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may precede the onset of IBD, lead to a reactivation of quiescent IBD, or exacerbate already active IBD in humans.32-35 In an adult case-control study, Felder et al compared the use of NSAIDs in 60 patients hospitalized for exacerbations of IBD, either ulcerative colitis or Crohn's disease, to that of 62 out-patients with irritable bowel syndrome.36 At least 31 of the IBD patients (35 of the ulcerative colitis patients) who used NSAIDs within 1 month of symptoms developed the onset or an exacerbation of IBD, whereas only 2 of the irritable bowel patients experienced aggravation of their symptoms after similar NSAID use. In a retrospective review of initial office visit records of adult out-patients with either Crohn's disease (112 initial visits) or ulcerative colitis (80 initial visits), Bonner et al did not find any association between NSAID use and active IBD.37 Also, another short report suggested...

Recognizing Other Types of Diabetes

I Diabetes due to hormone treatments for other diseases If you take hormones to treat a disease other than diabetes, those hormones could cause diabetes in your body. The hormone that is most likely to cause diabetes in this situation is hydrocortisone, an anti-inflammatory agent used in diseases of inflammation, such as arthritis. (Similar drugs are prednisone and dexamethasone.) If you take hydrocortisone and you have the symptoms of diabetes listed in earlier sections of this chapter, talk to your doctor.

Summary and recommendations

Glucosamine and chondroitin sulfate have been used as nutriceuticals since 1969.11 They are believed to ameliorate the symptoms of osteoarthritis by reducing inflammation and by aiding in the restoration of normal cartilage.53,54 While animal studies have shown positive effects, research in humans is still equivocal. However, as yet, no firm conclusions can be made about these homeopathic remedies.55 A recommendation for the use of a nonpharmacological treatment for symptomatic osteo-arthritis of the hip and knee includes exercise, both aerobic and strength training, and diet. Exercise was found to be just as effective as NSAIDs for improvement in pain and function.56 The results of this study suggest that, in particular groups of individuals, supplement and drug therapy could be reduced or eliminated.

Series Editor Introduction

Cardiovascular and cerebrovascular diseases are the focus of the third section. Long-chain omega-3 fatty acids (LC PUFA) have been associated with reduced risk of CVD in survey studies for the past 50 years, and the potential mechanisms for reduction in risk continue to be elucidated, but include antiinflammatory, antiarrhythmic and antiproliferative actions at the cellular level and beneficial alterations in lipid profiles, especially triglycerides. This chapter contains a detailed description of the effects of LC PUFA on lipids, lipoproteins, triglycerides, apolipoprotein levels, turnover, and metabolism. New data on the role of LC PUFA in diabetics are also included. LC PUFA are examples of good fats. The next chapter describes the adverse effects to the cardiovascular system caused by trans fats, examples of bad fats. The majority of trans fats are found in foods that contained hydrogenated oils or contained fats that went through other production processes that resulted in their...

Therapy to Prevent Recurrent Gastrointestinal Bleeding

Many clinical decisions will deal with therapeutic options. For example, a 64-year-old black male is admitted to the intensive care unit after presenting with hematemesis and near syncope. His previous medical history is notable for osteoarthritis, for which he takes a nonsteroidal antiinflammatory agent bid. He has been adequately resuscitated and an upper endoscopy reveals a 1 cm bleeding gastric ulcer. The lesion is treated endoscopically. The senior medicine resident inquires about the need for acid suppression medications to reduce the risk of recurrent bleeding.

Historical background

Glucocorticoids are widely used as one of the most efficacious medicines against various inflammatory and immunological diseases such as rheumatoid arthritis, systemic lupus erythematosus and bronchial asthma. Their anti-inflammatory action is mediated by inhibition of arachidonic acid release, a precursor of prostaglandins (PGs), hydroxyeicosatetraenoic acids (HFTEs) and leukotrienes (LTs). Phos-pholipase A, (PLA2) and alkylphospholipids, a precursor of platelet-activating factor (PAF), in biomem-branes have been considered as the key enzyme and the major source of arachidonic acid, respectively. Anti-inflammatory steroids also inhibit the forma tion of both PAF and its inactive lyso-form (deacylated molecule). Since most of the antiinflammatory actions of glucocorticoids are inhibited in vivo and in vitro by inhibitors of protein synthesis as well as mRNA synthesis, it was proposed that the anti-inflammatory action of glucocorticoids is partly, if not exclusively, mediated through...

Biological actions and possible physiological roles

Initial efforts have been made to identify and characterize the annexins, particularly annexin I and II, as possible second messengers in response to antiinflammatory steroids. The observations to date have shown that these recombinant annexins are able to mimic a part, if not all, of the anti-inflammatory action of glucocorticoids, while antibodies against annexins diminish such actions (Table 2). Even some of their fragments containing the N-terminus exhibit similar but weak anti-inflammatory actions. The inflammatory reactions inhibited by annexins and their fragments include not only the release of arachi-donate and its metabolites and the formation of PAF but also neutrophil chemotaxis and release of lyso-zymes. The cytotoxic reaction by cytotoxic T cells and NK cells is also inhibited by both annexins and glucocorticoids. Although the annexin I and II genes contain GRE sequences in their 5'-flanking regions, thus implicating transcriptional regulation by glucocorticoids,...

Clinical examples of free radical antioxidant and immune function interactions

With regard to intervention studies, vitamin E has been examined to the greatest extent in patients with RA and other arthritic conditions. Three studies in RA patients suggest that vitamin E at high levels, but not at dietary intake levels, reduced pain. Vitamin E supplementation produced significant pain relief in four other studies. There was also a consistent finding of vitamin E-related antiinflammatory activity, although the studies involved a limited number of subjects.

St St Use the median to abolish those wretched outliers

2.2.3 Mode - a global assessment variable for the response to an anti-inflammatory drug The condition of a series of patients with arthritis is recorded using a global assessment variable. This is a composite measure that takes account of both objective measures of the degree of inflammation of a patient's joints and subjective measures of the restrictions on their quality of life. It is set up so that higher scores represent better condition. The patients are then switched to a new anti-inflammatory product for 3 months and re-assessed using the same global measure. We then calculate the change in score for each individual. A positive score indicates an improvement and a negative one a deterioration in the patient's condition. Sixty patients participated and the results are shown in Table 2.3. Table 2.3 Individual changes in a global assessment variable following treatment with an anti-inflammatory (61 patients) Table 2.3 Individual changes in a global assessment variable following...

The Good the Bad and the Promising

The use of IFNP in the treatment of multiple sclerosis (MS) is well established, although its mechanism of its action is mostly unknown. The beneficial effects of IFNP in preventing relapsing episodes may be due to a combination of anti-inflammatory, antiproliferative, and pro-apoptotic responses (Hafler 2004). Both experimental rheumatoid arthritis and myasthenia gravis also appear to benefit from treatment with IFN (Deng et al. 1996).

Inhibition Of Ice And Effect On Il18

Because inhibition of IL-i activity with IL-iRa in patients with rheumatoid arthritis has improved the clinical outcome (27), attention has focused on the effect of inhibiting IL-i8, since processing and secretion of this cytokine involves ICE. Indeed, inhibitors of ICE have been used in the mouse collagen arthritis model to reduce disease (ii3). Two irreversible ICE inhibitors, VE-i3,045 and VE-i6,084, were injected into DBA iJ mice with collagen-induced arthritis. Pretreatment significantly delayed the onset of inflammation and was more effective than either indomethacin or methyl prednisolone. The ICE inhibitors were also effective the progression of arthritis when administered to mice with established disease. Although these studies are similar to those using anti-IL-ip in this model (ii4), they do not rule out a possible role for inhibiting the release of IL-i8. However, the role of IFN-y (as a downstream event in IL-i8 biology) is less impressive in this model than IL-ip (ii5)....

P Saxifraga And P Major

The fresh root can be chewed for toothache and paralysis of the tongue (Grieve, 1998) and is used to prepare a tincture which is administered for sore throats, pharyngitis, laryngitis, and bronchitis (Schauenberg and Paris, 1990). Infusions or tinctures of the drug are employed as a gargle for inflammation of the mouth and throat (Wichtl, 1994). The rootstock (used fresh or dried) has antiinflammatory and mildly astringent properties (Launert, 1989).

Lateral elbow pain 1 Lateral epicondylitis

Proper racquet size and proper backhand technique can lessen the severity of pain. The first line of treatment is rest, a short course of antiinflammatory medicine, and a wrist splint. Specialized braces that increase pressure in the forearm have also been used with success.

Il10 Production In Inflammatory Diseases In Humans

The role of IL-10 in systemic inflammatory responses in humans has been recently investigated in detail, and some of the results are startling. In healthy individuals, serum IL-10 levels are below the detection limit of most assays (5-10 pg mL), but a substantial fraction (57 ) of patients with grampositive and gram-negative sepsis do have detectable circulating IL-10 (range 12-2740 pg mL), and serum concentrations are higher in patients with septic shock (85). Indeed, another study reported that IL-10 serum levels in septic patients were related to the severity of sepsis and organ failure (86). In severe meningococcal septic shock in children, very high IL-10 serum concentrations (median 6021 pg mL range 137-24,600 pg mL) were reported, and nonsurvi-vors had higher levels than survivors (87). These findings were initially interpreted to reflect an anti-inflammatory response that was secondary to release of cytokines such as TNF-a, but recent data have cast doubt on this view. In a...

Failure of Medical Treatment

Fulminant or unresponsive first attack is usually an indication for emergency surgical treatment and was previously discussed. Intractable disease is the most common indication for surgical treatment in ulcerative colitis. Criteria of intractability are frequently difficult to define since intractable disease may have a variety of manifestations. This group includes patients with persistent symptoms and inability to achieve remission despite adequate medical treatment with anti-inflammatory or immuno-suppressive medications. The stubborn insistence on medical therapy in these patients leads to further deterioration in health and performance status making impending surgical therapy more difficult and hazardous. Another group of patients with intractable disease are those who require continuous corticosteroid therapy to maintain remission. These patients are steroid dependent and experience a relapse of symptoms as soon as the dose of steroids is reduced or withdrawn. They should be...

Supplemental Reading

Best Pract Res Clin Gastroenterol 2001 15 433-45. Graham DY. Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole or prevention of gastric or duodenal ulcers among chronic NSAID users. Helicobacter 2002 7 1-8. Graham DY. Nonsteroidal anti-inflammatory drugs, Helicobacter pylori, and ulcers where we stand. Am J Gastroenterol 1996 91 2080-6. Graham DY. NSAIDs, Helicobacter pylori, and Pandora's Box. N Engl J Med 2002 347 2162-4. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease a meta-analysis. Lancet 2002 359 14-22. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995 123 241-9. Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin...

Cardiovascular Diseases and Renal Failure

Given the better gastrointestinal (GI) safety profile of COX-2 inhibitors over conventional NSAIDs, COX-2 inhibitors are the preferred anti-inflammatory drugs for moderate to high risk patients (Table 24-3) who receive concomitant low dose aspirin. Unfortunately, low dose aspirin itself is associated with a substantial risk of UGI complications. Current data suggest concomitant low dose aspirin partially or completely negates the beneficial safety effects of COX-2 inhibitors. Thus, patients on low dose aspirin who require anti-inflammatory therapy, regardless of NSAIDs or COX-2 inhibitors, should receive cotherapy with an anti- TABLE 24-3. Risk Stratification and Strategies to Prevent Nonsteroidal Anti-Inflammatory Drug-Induced Upper Gastrointestinal Complications TABLE 24-3. Risk Stratification and Strategies to Prevent Nonsteroidal Anti-Inflammatory Drug-Induced Upper Gastrointestinal Complications COX-2 Cyclooxygenase-2-inhibitors H2RA H2 receptor antagonist NSAID nonsteroidal...

Francis K L ChanMD and David Y GrahamMD

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world. For example, there were more than 111 million NSAID prescriptions written in 2000 in the United States. NSAID use is associated with an increase in the risk of clinical upper gastrointestinal (UGI) events including symptomatic ulcer and ulcer complications (ie, bleeding, perforation, and gastric outlet obstruction). The individual risk of UGI complications in average risk NSAID users is estimated to be between 2 to 4 per year (or 2 to 4 per 100 patient years). Despite this relatively low frequency of untoward events, the high volume of use results in an estimated 16,500 deaths annually among arthritis patients from the gastrointestinal (GI) toxicity of NSAIDs. in addition to serious complications, up to 50 of NSAID users experience dyspepsia. The presence of dyspepsia has little or no correlation with the presence of gas-troduodenal ulcers and the presence of dyspepsia is, at most,...

Drug Therapy Conventional and Alternative Therapies

Pentoxifylline (PTX) is a nonselective phosphodiesterase inhibitor which increases intracellular concentrations of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, and decreases production of proinflammatory chemokines cytokines, including TNF. Akriviadis and colleagues performed a prospective, randomized, double blind clinical trial of PTX in severe alcoholic hepatitis (DF > 32). Forty-nine patients received 400 mg of PTX orally 3 times daily and 52 received placebo (vitamin B12) for 4 weeks. PTX treatment improved survival. Twelve patients on PTX died (24.5 ) compared with 24 (46 ) patients on placebo. PTX also decreased hepatorenal syndrome as a cause of death. Six of the 12 (50 ) PTX-treated patients who died did so of renal failure compared with 22 of the 24 (92 ) control patients who died of renal failure. Multivariate analysis revealed age, serum creatinine at randomization, and treatment with PTX as independent factors associated with survival....

Didronel etidronate is usually prescribed for Pagets disease Is it ever prescribed for osteoporosis

The treatment of choice for Paget's is a bisphosphonate. Bisphosphonates Actonel, Fosamax, and Didronel are FDA-approved for the treatment of Paget's. Unlike the longer dosing regimens of other bisphosphonates, Didronel is generally prescribed for only two weeks to three months at a time depending on the dosage, with a rest period off the medication lasting at least three months. This regimen is usually repeated for about two years. Didronel is taken on an empty stomach without eating or drinking for two hours after taking it. Didronel should still be prescribed with caution in those with upper intestinal disorders. The most common side effects include nausea, diarrhea, and flatulence. Medications that cause stomach upset, such as non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, or aspirin, can increase the risk for ulcer or heartburn. Table 11 has information on Didronel.

Are there any medications that I should adjust or stop taking while Im being treated for osteoporosis

Presumably, you are taking prescription medications that are important to the treatment of your medical conditions. However, it's very important for you to be taking the smallest dosage that gives you the maximum benefit of any medication. Sometimes a medicine is prescribed by one clinician who is unaware of medication that you are taking that was prescribed by a different clinician. So, you need to be certain that all of your clinicians know about all of the medications you are taking. In addition, there are some over-the-counter medications such as non-steroidal anti-inflammatory drugs (NSAIDS), like ibuprofen, aspirin, and naproxen, and antacids that can increase side effects or interfere with your new medications for osteoporosis.

Acetaminophen buffered

Action Kinetics Acetaminophen decreases fever by an effect on the hypothalamus leading to sweating and vasodilation. It also inhibits the effect of pyrogens on the hypothalam-ic heat-regulating centers. It may cause analgesia by inhibiting CNS prostaglandin synthesis however, due to minimal effects on peripheral prostaglandin synthesis, acetaminophen has no anti-inflammatory or uricosuric effects. It does not cause any anticoagulant effect or ulceration of the GI tract. The antipyretic

Differential Diagnosis of the Painful

Anterior Soft Tissues Neck

Generally, the acute management of groin pain suspected to be athletic pubalgia is conservative, and includes rest, ice, compression, anti-inflammatory medications, and massage.10 When the process continues over several months and the athlete cannot return to previously expected activity because of pain, an operation should be considered. Surgical treatment of athletic pubalgia requires a broad surgical reattachment at the inferolateral edge of the rectus muscle with its fascial investments to the pubis and adjacent anterior ligaments. We also perform an anterior and lateral release of the epimysium of the adductor fascia in order to expand this compartment. The epimysium is the layer of connective tissue that encloses the entire muscle. This kind of fascial release is often very successful in relieving the adductor symptoms in athletic pubalgia.11 When sacroiliitis is a manifestation of an underlying spondyloarthropathy, treatment is dictated by the underlying inflammatory disease....

Correlates with Their Suppressive Capacity in Certain Models

The observation that effector memory-like Tregs express certain adhesion molecules and chemokine receptors that allow their efficient migration into inflamed sites has important implications for the use of such molecules as targets for anti-inflammatory therapies. Inhibition of migratory functions might not only prevent the infiltration of effector cells but also that of highly effective adaptive Tregs.

Interleukin10 Protein Therapy

Due to its anti-inflammatory and immunomodulatory effects recombinant IL-10 protein has been applied in various animal models of immune dysregulation, e.g., in autoimmune diseases (rheumatoid arthritis, experimental autoimmune encephalitis, diabetes, inflammatory bowel disease or psoriasis, for review see ref. 1). In 1995 the first study using recombinant IL-10 in patients has been performed. It showed that systemic application of IL-10 has no serious side effects and is well tolerated by the patients.2 Recent data from our group demonstrated its efficacy and safety in psoriasis patients particularly in preventing of relapse (for review see ref. 3). IL-10 is generally seen as a anti-inflammatory and immunomodulatory cytokine, however, recent data suggest that IL-10 might also express pro-inflammatory properties. It can stimulate NK cells and B cells, particularly at higher doses. Kinetic studies in patients have shown that at a daily dose > 10 g kg IL-10 shows increasing evidence...

TABLE 773 Treatment of Fulminant Colitis

Sulfasalazine (Azulfidine), 3 to 4 g day, has been shown to be effective in treating patients with mild to moderate active Crohn's disease. The mechanism of action is not known but is presumed to be through the topical action of 5-aminosalicylic acid, which is released by the action of colonic bacteria on sulfasalazine. Sulfapyridine is also a by-product of this breakdown. Many of the toxic side effects of sulfasalazine are attributable to sulfapyrizine. These include nausea, vomiting, anorexia, epigastric distress, arthralgias, headache, diarrhea, male infertility, and hypersensitivity reactions (pericarditis, pleuritis, pancreatitis, arthritis, and rash). Because of the toxicity profile associated with sulfasalazine, 5-aminosalicylic derivative agents are now available for either oral or topical use. A slow, timed-release mesalamine (Pentasa) 4 g day or a pH-dependent release mesalamine (Asacol, Claversal, Salofalk) 2 to 4 g day have the primary advantage of delivery into the colon....

Therapeutic Potential of Cannabinoid Based Drugs

Cannabinoid-based drugs modeled on cannabinoids originally isolated from marijuana are now known to significantly impact the functioning of the endocannabinoid system of mammals. This system operates not only in the brain but also in organs and tissues in the periphery including the immune system. Natural and synthetic cannabinoids are tricyclic terpenes, whereas the endogenous physiological ligands are eicosanoids. Several receptors for these compounds have been extensively described, CB1 and CB2, and are G protein-coupled receptors however, cannabinoid-based drugs are also demonstrated to function independently of these receptors. Cannabinoids regulate many physiological functions and their impact on immunity is generally antiinflammatory as powerful modulators of the cytokine cascade. This anti-inflammatory potency has led to the testing of these drugs in chronic inflammatory laboratory paradigms and even in some human diseases. Psychoactive and nonpsychoactive...

Inhibition of interleukin1

Gene family and binds IL-1R type I, a receptor capable of transducing signals, with similar affinity to that of IL-la and IL-l(3. However, unique in cytokine biology, no signal is transduced upon Il.-lRa binding to IL-1R. It is speculated that no signal is transduced because IL-IRa fails to bind the IL-l receptor accessory protein (IL-lR-AcP), thus inhibiting the formation of the IL-l receptor hetero-dimer complex required for signal transduction. IL-IRa is produced by the same cells that secrete IL-l however, the expression of IL-IRa is regulated by different types of stimuli including complexed IgG and anti-inflammatory cytokines. In addition, II.-1 and IL-IRa exist in various forms (i.e. secreted and intracellular). The actual extent of the inhibitory activity of IL-IRa in vivo is unclear. Due to the fact that occupancy of only a few membrane IL-1 type I receptors is sufficient to generate a biological response, the concentration of IL-IRa (compared to IL-l) needed to interfere...

In Vivo Pharmacological Activities A

ISIS 2302 is a phosphoro-thioate oligonucleotide inhibitor of human ICAM-1. It has been demonstrated to reduce ICAM-1 levels in a number of organs in a variety of animal models and to result in potent anti-inflammatory effects (for review, see Ref. 241). ISIS 2302 has been evaluated in a number of clinical trials in patients with inflammatory diseases (for review, see Ref. 242). The drug was evaluated in a randomized placebo-controlled phase Ila trial in 43 patients with moderate to severe rheumatoid arthritis (243). In this trial the effects of 0.5, 1.0, and 2.0 mg kg i.v. three times weekly for 1 month were compared to placebo. The 0.5 and 2.0 mg kg doses resulted in prolonged improvement in rheumatoid arthritis activity, compared to placebo. All doses were extremely well tolerated. ISIS 2302 was evaluated both by i.v. and topical routes as a potential therapeutic for patients with psoriasis the dosing for the i.v. study was equivalent to that used for the...

Nicole R Bianco Seon Hee Kim Adrian E Morelli and Paul D Robbins

Initial studies in our laboratory were focused on the use of dendritic cells (DC) genetically modified to express Th2-derived cytokines (i.e., interleukin IL -4 and IL-10) or apoptotic proteins (i.e., Fas Ligand FasL ) to reduce inflammation in a mouse model of experimentally induced arthritis. Exosomes are nano-sized vesicles (40-100 nm diameter) released by different cell types, including DC, that contain many of the proteins thought to be involved in regulating the immune response. We have demonstrated that exosomes derived from immature DC treated with immunomodulatory cytokines (i.e., IL-10, IL-4) are able to inhibit inflammation in a murine footpad model of delayed-type hypersensitivity (DTH) and reduce the severity of established collagen-induced arthritis (CIA). In fact, the exosomes were as therapeutic as the parental DC. Because purified DC-derived exosomes are very stable vesicles, they may be a better approach for future treatment of arthritis and other autoimmune...

Discharge And Home Maintenance Guidelines

Ensure that the patient understands the need to rest every hour, space work out over several days, and get at least 8 hours of sleep at night. Ensure that the patient knows whom to call in the event of sudden severe pain (as in a subluxation) or general worsening of the existing condition. Determine whether a home care agency needs to evaluate the home for safety equipment, such as rails and grab bars, and whether ongoing supervision is required. Instruct patients on salicylates that they may need periodic laboratory monitoring of liver and kidney functioning and that they should consider drug interactions. Review patient medication regimen for interactions with salicylates. Some drugs that potentially are affected by salicylates include anticoagulants, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), urine acidifiers, furosemide, para-aminobenzoic acid, certain antacids, phenobarbital, methotrexate, sulfonylureas, insulin, beta-adrenergic blockers, spironolactone, and...

PlGF as a Primary Vascular Inflammatory Instigator

In summary, PlGF plasma levels represent a powerful and reliable clinical biomarker of vascular inflammation and adverse outcome in patients with ACS. Measuring PlGF levels significantly extends the predictive and prognostic information gained from traditional inflammatory markers in ACS. Most notably, because the proinflammatory effects of PlGF can be specifically inhibited by blocking its receptor Flt-1, these findings may also provide a rationale for a novel anti-inflammatory therapeutic target in patients with CAD (43).

Historical and physiological background

Until 1949 the main clinical use of glucocorticoids was for replacement therapy of patients with hormone deficiency. That year the biomedical world was electrified by the totally unexpected discovery that large doses of cortisone exerted powerful antiinflammatory activity, dramatically alleviating the symptoms of rheumatoid arthritis. This development led to a spectacular rise in applications of glucocorticoids - the 'miracle drugs' of the 1950s - and set the stage for much of their current clinical use. Innumerable derivatives of the glucocorticoids were synthesISBN 0-12-226765-6

Paraneoplastic Arthropathies Of Solid Tumours

Rheumatologic symptoms are usually reluctant to nonsteroidal anti-inflammatory agents, corticosteroids, ganglion blockade or physical therapy but chemotherapy may offer some improvement 10 . Successful removal of a tumour may also be followed by a dramatic improvement in pain and vasomotor disturbances, but predictably, contractures improve at a slower rate 14 . The treatment of HOA is rather disappointing. Successful treatment of the underlying diseases is usually associated with a rapid resolution of the problem. However, in most cases with lung cancer, the disease is often in the advanced state, making successful treatment difficult. Although nonsteroidal anti-inflammatory drugs and colchicine might be successful in pain relieving, many times, however, the symptoms do not respond to therapy 24 .

M Kryworuchko W David Creery and Ashok Kumar Abstract

Interleukin-10 (IL-10) is a pleiotropic cytokine produced by monocytes macrophages, B cells, and various subsets of T cells including T helper type 2 (Th2), Th0 cells, and regulatory T (Tr) cells and to a lesser extent by Th1 cells. IL-10 exerts diverse effects on a number of hemopoeitic cell types that include regulation of proliferation and differentiation of most immune cells. The main biological function of IL-10 appears to be immunosuppressive and anti-inflammatory in nature and therefore, it has been exploited therapeutically for the treatment of various autoimmune disorders such as inflammatory bowel disease, psoriasis and rheumatoid arthritis in Phase II and Phase III clinical trials. Studies of IL-10 manipulation by employing IL-10 knock out and IL-10 transgenic animal models have revealed a central role for IL-10 in the immunopathogenesis of a number of infectious diseases. Overall, the results suggest that in infectious diseases wherein inflammation constitutes a critical...

In Vitro and In Vivo Functional Testing of Exosomes

To investigate the antiinflammatory effect of DC-derived exosomes in vivo, a DTH model in C57B1 6 mice is used. C57B1 6 mice are sensitized by injecting 100 pg of antigen (KLH or OVA) emulsified 1 1 in CFA at a single dorsal site. Two weeks later, one hind footpad of the immunized mouse is injected with 1 pg of exosomes (in 50 pL of PBS), 12-24 h before challenging with antigen. The contra-lateral footpad receives an equal volume of PBS as an injection control. Mice are then challenged in both footpads by injecting 20 pg of antigen dissolved in 20 pL of PBS. Footpad swelling is measured with a spring-loaded caliper at 24, 48, and 72 h postinjection. Results are expressed as the difference in swelling (X0.01 mm), before and after antigen boost injection.

Effect of HA1077 on Cerebral Infarction

In the above-mentioned double-blind trial of HA1077 in patients with SAH, the brain-protective effect seen by a decrease in cerebral infarction on CT scans was most remarkable (Table 3). In experiments in rats, the effects of HA1077 on cerebral infarction were shown in the carotid occlusion model (Tsuchiya et al. 1993 Satoh et al. 1999a). The effect of HA1077 on cerebral ischemia is twofold. One positive effect is an increase in collateral circulation in penumbra through dilation of the cerebral arteries, a second positive effect is an anti-inflammatory action. HA1077 has been shown by HMPAO (Tc-99m hexamethyl propyleneamine oxime) to increase rCBF in patients after SAH. Interestingly, it increased rCBF in the region of cerebral vasospasm without changing blood flow in normal regions. In other words, it increased rCBF more specifically in spastic regions, thus avoiding development of a so-called steal phenomenon. This is unique to HA1077. It is usual for calci

Antibodydependent immunotherapy

Interleukin 1 receptor antagonist has been used in sepsis without success, but recent trials in rheumatoid arthritis by Amgen Inc. have shown a trend to some benefit, not so much in reducing inflammation, but in reducing the rate of joint destruction as assessed by serial X-rays of the hands.

Approach To Nephrotic Syndrome

In adults, one third of patients with nephrotic syndrome have a systemic-disease that involves the kidneys, such as diabetes or lupus the remainder have a primary renal disease, with one of four pathologic lesions minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis (FSGS). or membranoproliferative glomerulonephritis (MPGN). Thus, a new diagnosis of nephrotic syndrome warrants further investigation into an underlying systemic disease. Common tests include serum glucose and glycosylated hemoglobin levels to evaluate for diabetes, antinuclear antibody (ANA) to screen for systemic lupus erythematosus, serum and urine protein electrophoresis to look for multiple myeloma or amyloidosis, and viral serologies, because HIV and viral hepatitis can cause nephrosis. Less common causes include various cancers, medications such as nonsteroidal antiinflammatory drugs (NSAIDs). heavy metals such as mercury, and hereditary renal conditions. Of these causes, diabetes...

Transient Tenosynovitis of the

Transient Toxic Synovitis

Admission to hospital is necessary only for management of SCFE, other hip fractures, and septic arthritis of the hip. Once these diagnostic considerations are effectively eliminated, the child with suspected transient tenosynovitis of the hip can be managed as an outpatient. Weight bearing is eliminated, and anti-inflammatory agents are recommended until the child's hip is painless and range of motion returns to normal (3 to Z days). Some authors recommend an additional period of rest (Z to 10 days) after symptoms have resolved. Antibiotics are of no value glucocorticoids are not recommended.

Carpal tarsal osteolysis

No definitive treatment currently exists for CTO. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be administered for analgesia during painful episodes, and physical therapy and splints worn for stabilization can provide some relief during symptomatic periods and help maintain functional positions, but they do not influence the progression of the disease 47 . Over time, the entire carpus may be resorbed, resulting in gross instability and dislocation of the hand (Fig. 6). Although the wrist is unstable, extrinsic and intrinsic musculotendinous function is preserved, as is active flexion and extension of the metacarpophalangeal and interphalangeal joints. Manual dexterity may remain surprisingly functional, albeit weak, and surgery is rarely indicated 3 .

Facet Joints in Spinal Pain

Facet Joint Injection Side Effects

Occasional improvement with heat or anti-inflammatory drugs Positive response (pain relief) with joint injection Joint injections may be requested for either diagnostic or therapeutic indications.7-9 Diagnostic injection may be requested to confirm a clinical suspicion of a facet-mediated pain syndrome. The joint selected for injection may be specifically requested or determined from imaging studies or physical examination. Intra-articular injection of steroid may be used for longer acting anti-inflammatory activity, and there are reports of long-term effectiveness in pain management (> 6 months pain relief) depending, of course, on the exact pathological process in the joint. Long-term pain relief appears to be most successful in treating posttraumatic facet syndrome, and injections may be useful to treat injuries of the whiplash and paraspinal strain types.

Clinical manifestations

ReA in HIV-positive patients has been widely documented. Some authors consider that CD4-positive lymphocyte subpopulation does not play a determinant role in ReA 33 . The pathogenesis of ReA seems to be linked to HLA-B27, which has been described as the major susceptibility factor for the disease 34 . The association between AIDS and ReA could be explained by the severe immunosuppression, which predisposes to the invasion by ar-thritogenic microorganisms. Furthermore, AIDS patients have a wide spectrum of gastrointestinal and genitourinary infections (Shigella sp, Chlamydia trachomatis, Entamoeba histolytica, Giardia lamblia, Cryptosporidium sp, Isospora belli, Candida sp, and cytomegalovirus). Some of these infections have been related to the pathogenesis of ReA, and are usually asymptomatic even in HIV-positive patients 20 , although other studies suggest the direct or reactive role of retrovirus in the genesis of ReA 15,35,36 . Only limited data are available, however, on synovial...

Effects of IL13 on monocytes and endothelial cells

The effects of IL-13 on monocytes macrophages and endothelial cells are similar to those of IL-4. IL-1 modulates the phenotype of both human and murine monocytes macrophages and it inhibits production of proinflammatory cytokines, chemokines and nitric-oxide by these cells. IL-13 inhibits synthesis of IL-la, IL-1 p, IL-6, IL-12, tumor necrosis factor a (TNE-a) and the chemokines IL-8, macrophage inflammatory protein (MlP-la) and MIP-1 3 by monocytes. In addition, it enhances production of the IL-1 receptor antagonist, which is a secreted protein with antiinflammatory properties. IL-13 also inhibits IL-1 (3 and TNFa production by synovial fluid macrophages from patients with rheumatoid arthritis, suggesting that IL-13 may have therapeutic potential in the treatment of inflammatory arthritis. This notion is supported by the observation that IL-13-producing cells attenuate collagen-induced arthritis in mice. IL-13 was also shown to suppress experimental autoimmune encephalomyelitis in...

Approach To Polyarticular Arthritis

Articular Manifestations

In polyarticular disease, the next diagnostic clue is the duration of symptoms. If symptoms are relatively acute (< 6 weeks), the major considerations are arthritis due to viral infection (such as hepatitis B or C, rubella, or parvovirus B19) or the earliest manifestation of a true rheumatic disease. Viral serologies and compatible clinical history of exposure often can make the diagnosis at this point and obviate need for further rheumatologic evaluation. Treatment of a viral arthritis usually is limited to symptom relief with nonsteroidal antiinflammatory drugs (NSAIDs) because the conditions are generally self-limited.

Arthritis Bibliographi

The first clinical description of a syndrome called podagra, a classic pattern of gout, was in the fifth century b.c. Despite its early recognition, gout continued to plague humankind until the middle of the twentieth century, when practical and effective therapy emerged. The introduction of allopurinol and nonsteroidal antiinflammatory drugs (NSAIDs) has made it possible to alter the course of the disease dramatically.

Disorders of the Soft Tissues

A bursa is a fluid-filled sac between a bone and a tendon or muscle that allows the tendon to slide smoothly over the bone. Bursitis occurs when repeated stress and overuse cause the bursa to become inflamed and swollen with excess fluid. Bursitis also can result from injury, rheumatoid arthritis, gout, or infection. Bursitis most often occurs in the shoulder but also can affect the hip, knee, elbow, Achilles tendon, or ankle. Often the nearby tendon also becomes swollen. Bursitis usually can be treated with rest, ice, and nonsteroidal anti-inflammatory medication. Occasionally it is necessary for a doctor to withdraw excess fluid from the bursa using a needle and syringe. If an infection is present, the doctor will prescribe antibiotics. If there is no infection, the doctor may inject a Treatment of tendinitis may include making changes in your activities or routine, receiving corticosteroid injections, taking nonsteroidal anti-inflammatory medications such as aspirin or ibuprofen,...

Role of IL1Mediated Inflammation in Tumor Angiogenesis

The IL-1Ra has been routinely used for alleviating clinical symptoms of rheumatoid arthritis patients, due to its anti-inflammatory features. We have hypothesized that it also has the potential to intervene in tumor growth. Indeed, we have shown that treatment of tumor-bearing mice with IL-1Ra, in controlled-release systems, reduced tumor growth and angiogenesis (Bar et al. 2004). These results were also confirmed by others (Elaraj et al. 2006).

Box 2 Triggering microbes of reactive arthritis

Intravesicular instillation of bacillus Calmette-Guerin is successfully used as a treatment for intermediate- and high-risk superficial bladder carcinoma. It has also been reported as a rare cause of ReA. A recent review found 48 papers reporting this complication of intravesicular bacillus Calmette-Guerin therapy 58 . This form of ReA generally responds to discontinuation of bacillus Calmette-Guerin therapy or nonsteroidal anti-inflammatory drugs however, it rarely can evolve into a chronic process.

Action Kinetics PO Onset

Min for analgesia and up to 1 week for anti-inflammatory effect. Peak plasma levels 1-2 hr (2-4 hr for sustained-release). Peak action for gout 24-36 hr swelling gradually disappears in 3-5 days. Peak activity for antirheumatic effect About 4 weeks. Duration 4-6 hr for analgesia and 1-2 weeks for anti-inflammatory effect. Therapeutic plasma levels 10-18 mcg mL. tV2 Approximately 5 hr (up to 6 hr for sustained-release). Plasma tV2 following IV in infants 12-20 hr, depending on age and dose. Approximately 90 plasma protein bound. Metabolized in the liver and excreted in both the urine and feces.

The Cascade of Inflammatory Signaling

Cells are regularly exposed to stress, which mainly consists of inflammatory stress and metabolic stress. Inflammatory stress is exerted by cytokines that are released in large quantities by immune cells in response to invading microorganisms or other pathophysiological signals. The main cytokines involved in the pathogenesis of type 2 diabetes are interleukin (IL)-ip, tumor necrosis factor-a (TNF-a), NF-kB, and IL-6, IL-18 and adipokines, which are considered as the main regulators of inflammation leptin, more recently introduced, and several others, such as monocyte chemoattrac-tant protein-1, suppressors of cytokine signaling proteins, resistin, angiotensinogen, and aromatase also are present with deleterious effects in diabetic pathogenesis. The characterization of these molecules helps to identify targeted diabetes treatment beyond the conventional interventions (lifestyle changes and pharmaceutical agents), and move toward the controlling of specific molecular pathways to...

Disorders of the Joints

Osteoarthritis is diagnosed based on your symptoms and the results of a physical examination. X rays usually are taken to confirm the diagnosis. There is no cure for osteoarthritis. Your doctor probably will prescribe a nonsteroidal anti-inflammatory drug to relieve symptoms. Severe episodes of inflammation may be treated by injecting a corticosteroid drug directly into the affected joint. Massage, heat treatments, and warm baths may help relieve symptoms. Regular, gentle exercise (such as walking or swimming) will help your joints stay flexible. Maintaining a healthy weight (see page 67) will reduce the strain on your joints. For some people doctors may recommend joint replacement (see page 310).

Nonhydroxamic Acid Nonpeptidic MMP Inhibitors

Bayer found that the known anti-inflammatory agent, fenbufen, possesses modest inhibitory activity against gelatinase-A, and has prepared more potent analogs, such as 18 (46). This compound features a carboxylic acid zinc binding group and a cyclic imide P1 substituent. A large P1' b iphenyl group ensures selectivity for the deep-pocket MMPs. A variety of nonpeptidic natural-product MMP inhibitors have been discovered by screening. These include pycnidione (19 Merck 89), futoenone derivatives (e.g., 20 OAS-1148 OsteoArthritis Sciences) (90), betulinic acid (21 Sterling Winthrop 91), gelastatins (e.g., 22 92), and tetracyclines such as aranciamycin and minocycline, for which chemical modification (e.g., 23 CMT-1) has enabled the separation of MMP activity from antibiotic activity (93,94). Two of these compounds feature a carboxylic acid that may serve as a ZBG for others, it is possible that a ring hydroxyl and or carbonyl chelates the active site zinc(II) ion. In the case of the...

Adventitious Organisms And Biotechnology

Mycobacteria have historically been considered to cause some of the most devastating of human diseases. Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis in humans and produces several substances that have been shown to be significant pyrogens. M. leprae is another infamous member of the genus. More recently, the acquired immune deficiency syndrome (AIDS) epidemic has brought about the emergence of another Mycobacterium of clinical significance M. avium (69). Mycobacteria are lipid-rich (up to 60 of the dry weight of the cell) and a host of lipids, glycolipids, and lipoproteins have been isolated from mycobacterial cell walls, including the unique acid mycolic acid (3). LAM has been widely studied due to its immunoregulatory and anti-inflammatory effects as well as macrophage activation and subsequent significant release of TNF-a at low levels (100ng mL). Furthermore, suggesting an LPS-like mode of action, polymixin B (a well-known LPS binding molecule) and...

Stiffness and contracture

Aspirating the bursal fluid for Gram's stain, culture, crystal examination, and cell count is most helpful, and findings can be diagnostic. Unfortunately, some patients are placed on antibiotics before specimens are taken, and the diagnosis remains elusive. The simultaneous use of antiinflammatory agents and antibiotics, although not technically graceful, may be prudent in some of these patients until the final culture results are available. Because Staphylococcus aureus is most commonly cultured, dicloxacillin or a cephalosporin should be started pending the results of the culture. In those patients with infection who do not respond to a 1- to 2-day course of oral antibiotics, intravenous therapy is indicated. Daily aspiration of the bursa is also mandatory.

Subacromial Decompression

Pathology of the acromioclavicular joint is seen frequently in the active and athletic populations primarily from trauma, and in the elderly from a degenerative process. Initial treatment is with nonsteroidal anti-inflammatory drugs and corticosteroid injections however, surgery can be used for those who fail conservative treatment. It is important to distinguish those patients who have AC joint pain from joint instability (in which a stabilization procedure may be warranted) or isolated meniscal pathology (in which an isolated menis-cal procedure may be indicated) from most patients who have focal AC osteo-arthritis. In this latter group, in which degenerative changes have occurred in the articulation, isolated excision of the AC joint is the treatment of choice.

Classification Antimetabolite

Action Kinetics Inhibits pyrimi-dine synthesis which results in anti-proliferative and anti-inflammatory effects. Serum half-life 14-15 days. Time to peak 6-12 hours. Uses Reduce the signs and symptoms of active rheumatoid arthritis and to retard structural damage as demonstrated by x-ray erosions and joint space narrowing. Contraindications Pregnancy or women who may become pregnant. Special Concerns Significant hepatic impairment, positive hepatitis B or C virus serologies. Side Effects Oral Stomatitis, gingivitis, candidiasis, enlarged salivary gland, tooth disorder, dry mouth, taste disturbances. GI Diarrhea, nausea, abdominal pain, dyspepsia, weight loss, anorexia, gastroenteritis, vomiting, cholelithiasis, colitis,

Joint Manifestations Arthralgia Arthritis and Ankylosing Spondylitis

The approach to arthralgia and arthritis type 1 is to treat the bowel disease flare. Controlling disease activity with steroids leads to remission of joint manifestations. When arthralgia is independent of bowel disease activity, however, it should be treated with paracetamol because nonsteroidal anti-inflammatory drugs may activate and exacerbate the bowel disease 27 . Type 2 arthritis and ankylosing spondylitis (the course of which is independent of the bowel disease) should be treated preferably with sul-phasalazine. Many studies have demonstrated the efficacy of this medication in patients with peripheral arthritis and, to a lesser degree, in spondylitis -especially in the long term. The use of methotrexate and 6-MP seems promising for controlling peripheral arthritis and spondylitis. In very severe and resistant cases, infliximab has been used successfully, but new randomised controlled trials are necessary 28 .

Energy Enzymes and Metabolism

Millions of people, including famous athletes such as hockey star Wayne Gretzky, baseball great Hank Aaron, and Olympic decathlete Bruce Jenner, suffer from crippling arthritis. Until recently, physicians prescribed aspirin to calm the swelling that plagues arthritic joints. Aspirin has a long tradition in medicine. For thousands of years, healers in many cultures knew that the bark of a willow tree had anti-inflammatory properties that reduced swelling and pain. In 1829, German chemists isolated the active ingredient in willow bark, and later in that century others modified it chemically to make an even more effective drug aspirin. While this drug was effective, it had several negative side effects, such as severe stomach irritation and reduced blood clotting. The search went on for a better anti-inflammatory drug one that would block COX only in the joints. During the 1990s, biochemists hit paydirt. They found that there are actually two COX enzymes, one that acts in the stomach and...

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