Anti-inflammatory Effects In Patients Research Articles

AS-150 Association of Platelet Reactivity and Endothelial Function and Anti-Inflammatory Effects in Patients with Stable Coronary Artery Disease

AS-150 Association of Platelet Reactivity and Endothelial Function and Anti-Inflammatory Effects in Patients with Stable Coronary Artery Disease

Letter by Shenhar-Tsarfaty et al Regarding Article, “Autonomic Shift and Increased Susceptibility to Infections After Acute Intracerebral Hemorrhage”

To the Editor: In the May issue of Stroke , we read with great interest the recent article by Sykora et al regarding the association of decreased baroreflex sensitivity with infections after intracerebral hemorrhage.1 The authors demonstrated decreased baroreflex sensitivity and an invasive procedure as independent predictors for postintracerebral hemorrhage infection, supporting the concept of autonomic shift toward sympathetic predominance as an independent risk of higher occurrence of infection in intracerebral hemorrhage. Although not discussed by the authors, their findings further confirm a critical role for the cholinergic–anti-inflammatory effect in patients with stroke, as was also shown in several …

Regular Daily Intake of Black Tea Improves Oxidative Stress Biomarkers and Decreases Serum C-Reactive Protein Levels in Type 2 Diabetic Patients

Background: This study was undertaken to evaluate the possible effects of different daily doses of black tea intake on certain oxidative stress, inflammatory and metabolic biomarkers in patients with type 2 diabetes mellitus (T2DM). Methods: Forty-six patients with known T2DM were randomly assigned either to the test (n = 23, 57.0 ± 7.9 years) or the control (n = 23, 55.4 ± 8.3 years) group. Following a one-week ‘run-in’ period, the test group received 150, 300, 450 and 600 ml of black tea extract (BTE) during the weeks 1, 2, 3 and 4, respectively. The control group received 150 ml BTE a day throughout the intervention period. Dietary, anthropometric and biochemical assessments were performed at the end of each week. Findings: Serum total antioxidant capacity was enhanced similarly in both test and control groups. However, daily intake of 2 cups of BTE by the test group showed a suppressing effect on serum malondialdehyde. Serum C-reactive protein significantly decreased and glutathione levels increased following the intake of 4 cups (600 ml) of BTE a day. Conclusion: Regular intake of BTE had anti-oxidative and anti-inflammatory effects in patients with T2DM. These findings may, to some extent, explain the mechanisms underlying the protective effects of drinking tea against cardiovascular disease.

Ketamine Attenuates Delirium After Cardiac Surgery With Cardiopulmonary Bypass

To determine if ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect in patients undergoing cardiac surgery using cardiopulmonary bypass. A prospective randomized study. A Veterans Affairs medical center. Cardiac surgical patients. Patients at least 55 years of age randomly received placebo (0.9% saline, n = 29) or an intravenous bolus of ketamine (0.5 mg/kg intravenously, n = 29) during anesthetic induction in the presence of fentanyl and etomidate. Delirium was assessed by using the Intensive Care Delirium Screening Checklist before and after surgery. Serum C-reactive protein concentrations were determined before and 1 day after surgery. The incidence of postoperative delirium was lower (p = 0.01, Fisher exact test) in patients receiving ketamine (3%) compared with placebo (31%). Postoperative C-reactive protein concentration was also lower (p < 0.05) in the ketamine-treated patients compared with the placebo-treated patients. The odds of developing postoperative delirium were greater for patients receiving placebo compared with ketamine treatment (odds ratio = 12.6; 95% confidence interval, 1.5-107.5; logistic regression). After cardiac surgery using cardiopulmonary bypass, ketamine attenuates postoperative delirium concomitant with an anti-inflammatory effect.

Effect of pine bark extract (Pycnogenol®) on symptoms of knee osteoarthritis

The safe and efficacious use of Pycnogenol (French maritime pine bark extract) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis (OA). The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind, placebo-controlled, randomly allocated trial with patients suffering from knee osteoarthritis stages I and II. 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo. Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period. Patients filled the Western Ontario and Mc Masters University (WOMAC) questionnaire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity. Following treatment with Pycnogenol patients reported an improvement of WOMAC index (p < 0.05), and a significant alleviation of pain by visual analogue scale (p < 0.04), the placebo had no effect. The use of analgesics diminished in the verum group but increased under the placebo. Treatment with Pycnogenol was well tolerated. Results show that Pycnogenol in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs.

The influence of tetracyclines on T cell activation.

Minocycline has been shown to have an anti-inflammatory effect in patients with rheumatoid arthritis (RA). Since there is evidence that RA is a T cell-mediated disease, we investigated the effect of minocycline on human T cell clones derived from the synovium of an RA patient. The T cells, when activated via the T cell receptor (TCR)/CD3 complex, were suppressed functionally by minocycline, resulting in a dose-dependent inhibition of T cell proliferation and reduction in production of IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Besides an inhibition of IL-2 production, minocycline exerted its effect on T cell proliferation by induction of a decreased IL-2 responsiveness. We showed that the chelating capacity of minocycline plays a crucial role in the inhibitory effect on T cell function, since the inhibitory effect on T cell proliferation could be annulled by addition of exogenous Ca2+. However, minocycline did not markedly influence the typical TCR/CD3-induced intracellular Ca2+ mobilization. Taken together, the results clearly indicate that minocycline has immunomodulating effects on human T cells.

Long-term exercise training decreases interleukin-6 (IL-6) serum levels in subjects with impaired glucose tolerance: effect of the −174G/C variant in IL-6 gene

Exercise training has been shown to have anti-inflammatory effects in patients with type 2 diabetes. Changes in interleukin-6 (IL-6) serum concentrations in response to training could contribute to these beneficial effects. However, there are heterogeneous data on whether circulating IL-6 is altered by exercise training. We therefore hypothesize that genetic factors modify the individual changes in IL-6 levels after long-term training. The -174G/C variant in the IL-6 gene was genotyped in 60 subjects with impaired glucose tolerance. For a 12-month interventional study, patients were randomized into three groups: a control group (n=16) was compared with one group, which underwent a standardized training program (n=24) and another group, which was treated with 4 mg rosiglitazone once daily (n=20). At baseline, after 1, 6, and 12 months, we measured anthropometric parameters and serum concentration of IL-6 and, at baseline and after 12 months, we determined glucose tolerance and fitness level. Only in subjects carrying the SNP -174C allele did long-term exercise training result in significantly reduced IL-6 serum concentrations. Multivariate linear regression analysis identified the IL-6 genotype as a significant predictor of changes in IL-6 serum concentrations independent of age, gender and improvement in body mass index, hemoglobin (Hb)A(1c), and fitness level in response to training. Genetic variants in the IL-6 gene significantly modify changes in IL-6 serum concentrations in response to long-term exercise training programs. Our data suggest that genetic factors are important determinants for the individual response to anti-inflammatory effects of exercise training.

Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvant‐induced polyarthritis

Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant-induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM-1 and EM-2 has never been investigated in OA and RA. We established a highly sensitive radioimmunoassay to detect EM-1 and EM-2. In patients with RA and patients with OA, immunohistochemistry for EM-1 and EM-2 was performed, and double-staining was used to identify EM-positive cells. The effects of EM-1 and EM-2 on the secretion of interleukin-6 (IL-6) and IL-8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM-1 were tested in a rat model of adjuvant-induced polyarthritis. EM-positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM-positive cells was higher in patients with OA than in those with RA. EM-1 inhibited synovial secretion of IL-6 in patients with RA and secretion of IL-8 in patients with RA and those with OA (maximum 10(-10)M). EM-2 inhibited IL-8 secretion only from RA tissue (maximum 10(-10)M). In rats with adjuvant-induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM-1 than was observed in controls. Rats with adjuvant-induced polyarthritis benefited from EM-1 treatment. EM-1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant-induced polyarthritis. Local enhancement of EM-1 might be an interesting therapeutic option in different forms of arthritis.

Probiotic administration in patients with ileal pouch–anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells

Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-beta [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1beta and Foxp3 mRNA expression was also evaluated. During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25(high) and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1beta mRNA expression, and a significant increase in Foxp3 mRNA expression. We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells.

‘Nonrespiratory sinus arrhythmia’ or ‘heart rate alternans’: Comments on the article by Gratadour et al. ‘Unusual sinus arrhythmia’

group 1 and 6 weeks post STEMI. These findings suggest that early initiation of a low-dose atovastatin treatment may exert beneficial anti-inflammatory effects in patients with STEMI, independently of the baseline cholesterol levels. Endothelial injury and activation characterises the acute phase of myocardial infarction and persists for many weeks post STEMI [4]. Von Willebrand factor (vWF), is a glycoprotein stimulating platelet adhesion to the subendothelium and a good marker of endothelial integrity [4]. Since statins exert a cytoprotective effect on vascular endothelium by modifying redox-state and preventing apoptosis [5], we hypothesized that early initiation of atorvastatin treatment would prevent the expected rise in vWF levels in patients with STEMI. Indeed, we observed that vWF was elevated 1 and 6 weeks post STEMI, an effect prevented by atorvastatin in normocholesterolemic patients. However, we found no change of tPA or PAI-1 levels during the post-STEMI period. In conclusion, we observed that early initiation of lowdose of atorvastatin treatment decreases the expression of IL6 and sVCAM-1 during the post STEMI. Also, we observed that early initiation of atorvastatin treatment post STEMI, decreases the release of vWF while it fails to modify the levels of PAI-1 or tPA. These data suggest that low-dose atorvastatin treatment has a beneficial effect in patients with recent STEMI, by modulating inflammatory response and decreasing endothelial injury and activation.

The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus

Diabetes mellitus (DM) and chronic inflammation are strongly related to increased cardiovascular risk. The purpose of this study was to evaluate whether an aerobic training programme would ameliorate inflammatory and anti-inflammatory markers in patients with type 2 DM. Interventional study. A total of 60 overweight individuals with type 2 DM, but without vascular complications, were randomly assigned to either a 6-month aerobic exercise training programme (four times/week, 45-60 min/session), designated as exercise group, or to the control group. All participants were on an oral antidiabetic regimen and none was receiving lipid-lowering medications. Anthropometric parameters, cardiorespiratory fitness, glycaemic and lipid profiles, high sensitivity C-reactive protein (hs CRP), adiponectin, interleukin (IL)-10, IL-18, tumour necrosis factor (TNF)-alpha, insulin, reciprocal index of homoeostasis model assessment (HOMA-IR), body fat and blood pressure (BP) were measured at baseline and at the end of the study. In comparison with baseline and control group, exercise-treated patients improved glucose control, lipid profile, exercise capacity (VO2 peak) and exhibited decreased insulin resistance and systolic BP considerably (P<0.05). Plasma adiponectin, TNF-alpha and body weight changed slightly across treatment (P>0.05), whereas diastolic BP and fat mass tended to decrease (P=0.071 and 0.061, respectively). Exercise training reduced hs CRP (from 0.48+/-0.16 to 0.29+/-0.2 mg/dl; P=0.04) and IL-18 (from 315.19+/-122.76 to 203.77+/-96.02 pg/ml; P=0.02). Moreover, exercise provided anti-inflammatory protection through IL-10 increment (P=0.039) and IL-18/IL-10 ratio downregulation (P=0.014). In multiple regression analysis, alteration in IL-18 was independently correlated with hs CRP and VO2 peak changes (P<0.05). Aerobic exercise training without significant weight loss improves metabolic profile and exerts anti-inflammatory effects in patients with type 2 DM.

Anti-inflammatory effect of 1-methylnicotinamide in contact hypersensitivity to oxazolone in mice; involvement of prostacyclin

1-methylnicotinamide (MNA) displays anti-inflammatory effects in patients with contact dermatitis, though the mechanisms involved remain unknown. Herein, we examined the anti-inflammatory effects of MNA and its parent molecule, nicotinamide, in the contact hypersensitivity reaction to oxazolone in CBA/J inbred mice. Feeding mice with MNA or nicotinamide (100 mg/kg, 10 days) resulted in the inhibition of the development of contact hypersensitivity reaction by 37% and 35%, respectively, as assessed by the magnitude of ear swelling. This effect was not associated with changes in the expression of adhesion molecules (CD49d + and CD54 +) on CD4 + and CD8 + oxazolone-specific T lymphocytes, the major cell component of an inflammatory infiltrate in contact hypersensitivity reaction. Furthermore, in the adoptive transfer model of contact hypersensitivity reaction, pretreatment of mice (recipients of oxazolone-specific T cells), with MNA, resulted in a remarkable anti-inflammatory effect (inhibition of contact hypersensitivity reaction by 66%). Interestingly, in the presence of prostanoid IP receptor antagonist R-3-(4-fluoro-phenyl)-2-[5-(4-fluoro-phenyl)-benzofuran-2-ylmethoxycarbonylamino]-propionic acid (RO-3244794) (10 mg/kg) the MNA was inactive. In summary, pretreatment with MNA profoundly attenuated contact hypersensitivity reaction in vivo. In particular, the vessel dependent phase of contact hypersensitivity reaction was affected, in spite of the fact that MNA did not alter the expression of adhesive molecules on oxazolone-specific T lymphocytes. However, the anti-inflammatory action of MNA was completely reversed by the antagonist of prostanoid IP receptor. Accordingly, our results demonstrate for the first time that anti-inflammatory properties of MNA are linked to endothelial, PGI 2-mediated mechanisms.

Insulin reduces myocardial ischemia–reperfusion injury via inhibition of leukocyte–endothelium adherence

Recent evidences indicate that Insulin exerts an anti-inflammatory effect in patients with acute myocardial infarction. Polymorphonuclear leukocytes (PMNs) activation and their interaction with coronary vascular endothelial cells (ECs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. This study was designed to investigate whether insulin inhibits PMN/EC adherence, which may contribute to reduced myocardial injury in MI/R. Anesthetized rabbits were subjected to MI/R (40 min/4 h) and randomly received saline, glucose-insulin-potassium (GIK) or GK respectively (4 ml/kg/h, i.v.).

Aprotinin Reduces Cardiac Troponin I Release and Inhibits Apoptosis of Polymorphonuclear Cells During Off-Pump Coronary Artery Bypass Surgery

In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. A prospective randomized clinical trial. University hospital. Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor alpha; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (p = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery.

Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes

Type 2 diabetes is characterized by increased acute phase serum proteins. They are also risk factors for cardiovascular disease. We wanted to study how improvement of glycemic control with pioglitazone or glibenclamide affects their serum concentrations. A total of 59 patients with Type 2 diabetes (age 57.3+/-1.2 yr, glycosylated hemoglobin (HbA1c) 8.3+/-0.7%, body mass index (BMI) 31.4+/-0.8 kg/m2) participated in the study. They were previously treated either with diet alone or in combination with one oral antihyperglycemic medicine. After a 1-week lead-in period on diet only, the patients were randomized to pioglitazone or glibenclamide. Blood samples for alpha-1-acid glycoprotein (A1GP), Creactive protein (CR P) and serum amyloid A (SAA) were taken before the treatments and during the therapy after 20 and 52 weeks. Baseline A1GP correlated with CR P (r=0.70, p<0.001) and fasting glucose (r=0.32, p<0.02). Baseline CR P correlated with HbA1c (r=0.26, p<0.05) and insulin (r=0.37, p<0.01). The anti-hyperglycemic effect was comparable with HbA1c levels decreasing both in the pioglitazone (from 8.18+/-0.09% to 7.63+/-0.17%, p<0.01) and glibenclamide (from 8.35+/-0.12% to 7.77+/-0.16%, p<0.01) groups. Pioglitazone treatment was associated with a reduction in A1GP at 20 weeks (p<0.001) and at 52 weeks (p<0.05) as compared to baseline. The significance remained also after comparison to glibenclamide therapy (p<0.001 and p<0.05, 20 and 52 weeks respectively). CR P was also more reduced in the pioglitazone group at 20 weeks of treatment (p<0.05). Inflammatory factors and markers of hyperglycemia are associated in patients with Type 2 diabetes. Pioglitazone treatment results in reduced A1GP concentration suggesting an anti-inflammatory effect.

Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment

Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU). To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria. Thirty-six patients with CU (18 with positive and 18 with negative autologous serum skin test) were studied, together with 10 control healthy subjects. All patients received levocetirizine 5 mg daily. Serum soluble cellular adhesion molecule (CAM) levels were determined by immunoenzymatic assay before and after the end of the study period. Disease activity was recorded according to the EAACI/GA(2)LEN/EDF scoring system. After levocetirizine therapy CAM levels decreased in patients with CU, significantly in the cases of ELAM-1 and P-selectin. Patients' clinical scores improved during regular antihistamine therapy. Levocetirizine 5 mg daily demonstrated a broad anti-inflammatory effect in patients with CU. The significant decrease in serum levels of ELAM-1 and P-selectin might reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin.

Clinical Response Is Associated with Elevated Plasma Interleukin-1 Receptor Antagonist During Selective Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis

Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while clinical remission was defined as CAI<or=4. Twenty-one of twenty-six patients (80.8%) responded to GMA. In the first session, plasma from responder patients showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In contrast, there was no change in IL-1ra in nonresponders. In conclusion, release of IL-1ra during GMA might be one mechanism of clinical efficacy associated with this therapy.

Acetaminophen, like conventional NSAIDs, may reduce synovitis in osteoarthritic knees

To determine the extent to which treatment of patients with symptomatic knee osteoarthritis (OA) with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (ACET) reduces total effusion volume and synovial tissue volume, as quantified by magnetic resonance imaging (MRI). Sequential pilot studies used subjects whose knee OA was treated with NSAIDs (n=10) or with ACET <or=4 g/day (n=20), respectively. After a five half-lives washout of their pain medication, the OA knee with the higher pain score >or=15 of 25 on the Western Ontario and McMaster Universities' pain scale underwent l.5T MRI. Effusion was quantified in axial short tau inversion recovery images; to measure synovial tissue volume, fat-suppressed T1-weighted axial images were obtained 3 min after i.v. injection of gadolinium contrast. After the initial MRI examination, patients resumed their customary pain medications until the severity of knee pain returned to baseline, when pain was again measured and the MRI was repeated. Pain severity after washout was similar in subjects taking ACET and NSAIDs. Reinstitution of ACET resulted in a 50% decrease in the mean of pain scores (P=1.7 x 10(-12)) that was comparable with that seen after the reinstitution of NSAID (49%, P=6.0 x 10(-7)). The mean total effusion volume measured during the flare of knee pain induced by the withdrawal of the two drugs was comparable (ACET 16.9 ml, NSAID 16.2 ml; P=0.884). Significant decreases in mean total effusion volume were observed after reinstitution of both ACET (-4.5 ml, P=0.009) and NSAID (-3.3 ml, P=0.013); the difference between drugs was not significant. Analyses of synovial volume yielded similar results. While uncontrolled and derived from small samples, these data suggest that ACET may have a significant anti-inflammatory effect in patients with knee OA, comparable with that achieved with NSAIDs, possibly through an effect on neurogenic inflammation. Joint pain is the clinical feature of OA that most often leads the affected individual to seek medical attention. Because many patients with OA improve symptomatically with the use of NSAIDs, it has been widely assumed that the pain of OA is due to synovial inflammation. However, the origins of OA pain are numerous and may vary from patient to patient and, within the same subject, from visit to visit. Although the articular cartilage is usually the site of the most obvious pathological changes in this disease, it is aneural and, therefore, is not the source of joint pain. However, in addition to the synovium, the subchondral bone, joint capsule, osteophytes, menisci, ligaments, periarticular tendons, entheses and bursae all contain nociceptive nerve endings, stimulation of which by chemical or physical mediators may be a basis for OA pain.

Pentosan Polysulfate

Pentosan polysulfate (pentosan polysulfate sodium; ELMIRON), a heparin-like, sulfated polysaccharide, is used to manage bladder pain and discomfort in adults with interstitial cystitis (IC). Preliminary clinical models suggest that pentosan polysulfate repairs damaged glycosaminoglycan (GAG) layers lining the urothelium and in vitro data suggest it may provide an anti-inflammatory effect in patients with IC. Pentosan polysulfate shows beneficial effects in a proportion of patients with IC in terms of the improvement of a patient's overall condition and the relief of pain, and it is a generally well tolerated therapy. It is the only US FDA-approved oral treatment for the relief of bladder pain or discomfort associated with IC, and data support its role as an important option in the treatment of patients with IC.

Macrolides: A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia?

Some macrolides have been found to exert anti-inflammatory effects. Lung diseases such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought to respond to the immunomodulatory properties of macrolides. We report three cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called cryptogenic organizing pneumonia, and three cases of radiation-related bronchiolitis obliterans organizing pneumonia that responded to macrolide therapy. An explanation of why macrolides may have anti-inflammatory effects in patients with these syndromes is discussed. These cases help to reinforce accumulating data that macrolides are beneficial as anti-inflammatory agents and organizing pneumonia may be another pulmonary disease that can benefit from such therapy.