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ID PMID Title PublicationDate abstract
21365954 [LE cells in synovial fluid: prevalence and diagnostic usefulness in rheumatic diseases]. 2010 This study was undertaken to determine the prevalence of LE cells in synovial fluid and their importance for the diagnosis of rheumatic disease. Synovial fluid was obtained from 631 patients: 31 with systemic lupus erythematosus (SLE), 337 with rheumatoid arthritis (RA), 4 with Still's disease, 9 with systemic scleroderma (SS), 27 with the overlap syndrome (RA/SLE), 132 with ankylosing spondylitis (AS), 57 with Reiter's syndrome, and 34 with psoriatic arthritis (PA). The fluid was centrifuged, precipitate smears were done and were May-Grünwald-Giemsa stained for cytologic assessment. The supernatant was collected for antinuclear antibody (ANA) testing. Physicochemical and serologic properties of the synovial fluid were routinely determined. All synovial fluids demonstrated signs of inflammation. The presence of LE cells was ascertained in five patients with SLE and nine patients with the overlap syndrome. In these cases, LE cells were accompanied by ANA. In addition, hematoxylin bodies were revealed in SLE patients. LE cells were observed in 2.6% of patients with RA but were not accompanied by ANA. Patients with SS, Still's disease, AS, Reiter's syndrome, and PA tested negative for LE cells. It appears from these results that LE cells are rarely present in the synovial fluid of patients with rheumatic diseases. In contrast, they occur in more than 40% of patients with the overlap syndrome and may thus be regarded as important for the diagnosis of this condition.
19797557 Oral health needs among adults in the United States with chronic diseases. 2009 Oct BACKGROUND: Oral and dental diseases may be associated with other chronic diseases. METHODS: Using data from the National Health and Nutrition Examination Survey 1999-2004, the authors calculated the prevalence of untreated dental diseases, self-reported poor oral health and the number of missing teeth for adults in the United States who had certain chronic diseases. The authors used multivariate analysis to determine whether these diseases were associated with indicators of dental disease after controlling for common risk factors. RESULTS: Participants with rheumatoid arthritis, diabetes or a liver condition were twice as likely to have an urgent need for dental treatment as were participants who did not have these diseases. After controlling for common risk factors, the authors found that arthritis, cardiovascular disease, diabetes, emphysema, hepatitis C virus, obesity and stroke still were associated with dental disease. CONCLUSIONS: The authors found a high burden of unmet dental care needs among participants with chronic diseases. This association held in the multivariate analysis, suggesting that some chronic diseases may increase the risk of developing dental disease, decrease utilization of dental care or both. CLINICAL IMPLICATIONS: Dental and medical care providers should work together to ensure that adults with chronic diseases receive regular dental care.
20178133 Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 ex 2010 Jun OBJECTIVE: Aurothiomalate is a disease-modifying antirheumatic drug that suppresses inflammation and retards cartilage degradation and bone erosion in arthritis. The molecular mechanisms of action of aurothiomalate are not known in detail. MAPK pathways are major signaling pathways in inflammation that regulate the production of many inflammatory and destructive factors in arthritis. The purpose of the present study was to investigate the effects of aurothiomalate on the activity of p38 MAPK and on the expression of MAPK phosphatase 1 (MKP-1), cyclooxygenase 2 (COX-2), matrix metalloproteinase 3 (MMP-3), and interleukin-6 (IL-6) in immortalized murine H4 chondrocytes and in intact human and murine cartilage. METHODS: Protein expression was examined by Western blotting or by enzyme-linked immunosorbent assay, and messenger RNA (mRNA) expression was examined by real-time reverse transcription-polymerase chain reaction analysis. The mediator role of MKP-1 was investigated by using small interfering RNA (siRNA) methods to down-regulated MKP-1 expression in chondrocytes in culture and by comparing the responses in intact cartilage from MKP-1-deficient and wild-type mice. The effects of aurothiomalate were also confirmed in human rheumatoid cartilage by using tissue samples obtained at the time of total knee replacement surgery. RESULTS: Aurothiomalate inhibited IL-1beta-induced COX-2 expression and prostaglandin E(2) production by destabilizing COX-2 mRNA, as did the p38 MAPK inhibitor SB203580. Interestingly, aurothiomalate also increased the expression of MKP-1 and reduced the IL-1beta-induced phosphorylation of p38 MAPK. Knockdown of MKP-1 by siRNA significantly impaired the ability of aurothiomalate to inhibit the phosphorylation of p38 MAPK and the expression of COX-2, MMP-3, and IL-6. Likewise, aurothiomalate reduced COX-2, MMP-3, and IL-6 expression in articular cartilage from patients with rheumatoid arthritis, as well as in articular cartilage from wild-type mice but not from MKP-1(-/-) mice. CONCLUSION: Our findings indicate a novel mechanism for the antiinflammatory and antierosive actions of aurothiomalate, through increased expression of MKP-1, which leads to reduced activation of p38 MAPK and suppressed expression of COX-2, MMP-3, and IL-6. The results suggest that manipulation of MKP-1 levels is a promising new mechanism to be directed in the search and development of novel antiinflammatory and antierosive compounds that have the good efficacy of gold compounds but not their toxicity.
19838390 Hip arthrodesis in children: A review of 28 patients. 2009 Oct BACKGROUND: The best method of treating intractable hip pain in an unsalvageable hip joint in a child is still a subject open to debate. We believe that hip arthrodesis in such patients provides a painless and stable hip for most activities of daily living in our challenging rural terrain. Therefore, we conducted this study to assess the functional ability of children with painful hip arthrosis treated by arthrodesis of the hip. MATERIALS AND METHODS: A retrospective evaluation of 28 children (out of 35) who had an arthrodesis of the hip performed between 1994 and 2008 was carried out. The average age was 14 years, with 12 males and 16 females. There was involvement of the right hip in 13 and left in 15 cases. The average duration of follow-up was 4.87 years. The preferred position of the hip for arthrodesis was 20-30 degrees of flexion, neutral abduction-adduction, and neutral rotation, irrespective of the method of fixation. RESULTS: The average duration of clinical and radiological arthrodesis was found to be 4 months (2-6 months). At the last follow-up, all patients were painfree and had good ambulatory capacity. The average Modified Harris Hip Score increased from 53 to 84 and the average post-surgical limb length discrepancy was 1.3 cm, which was well tolerated in all cases. Patients, however, had difficulty in squatting and had to modify their posture for foot care, putting on shoes, etc. Also, some patients complained of ipsilateral knee, contralateral hip, or low back pain with prolonged activity, but this was not severe enough to restrict activity except in one case that was known to have juvenile rheumatoid arthritis and needed ambulatory aid. CONCLUSION: In an environment where pathology generally presents very late and often in a dramatic manner, where the patient's socioeconomic status, understanding, compliance, and the logistics of follow-up are consistently a challenge in management, hip arthrodesis has been an important procedure for our patient group, with good short-term results and promising midterm, and, hopefully, long-term prospects. In our series of patients, we have been successful in restoring painfree mobility.
20706991 Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 a 2011 Feb We investigated the effects of hyaluronan (HA) on interleukin-1β (IL-1β)-stimulated matrix metalloproteinase (MMP)-13 production in human chondrocytes from patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Secreted levels of MMP-13 in conditioned media were detected by immunoblotting, while intracellular MMP-13 synthesis in articular cartilage was evaluated by immunofluorescence microscopic analysis. Mitogen-activated protein kinases (MAPKs), p38, extracellular signal-regulated kinases (ERK), and c-jun NH2-terminal kinase (JNK) were assessed by Western blotting. IL-1β (2 ng/ml) stimulates the secretion of MMP-13 in both OA and RA chondrocytes. Inhibition studies using specific MAPK inhibitors revealed that IL-1β induced MMP-13 via p38 in both OA and RA chondrocytes. HA down-regulates IL-1β-stimulated MMP-13 and phosphorylated p38 (p-p38) in a dose-dependent manner (0.1, 1, 2, and 4 mg/ml). When used at 4 mg/ml, HA inhibits p-p38 phosphorylation by more than 60%. In response to IL-1β, RA chondrocytes express a higher level of p-p38 than that of OA chondrocytes. Inhibition of CD44, using a blocking antibody, significantly reversed the inhibitory effect of HA on both MMP-13 and p-p38. Our study clearly shows that HA inhibits IL-1β-induced MMP-13 via its principal receptor, CD44, and subsequent intracellular p38 MAPK signaling in OA and RA chondrocytes.
18413443 Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthr 2009 May OBJECTIVE: We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes. METHODS: At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded. RESULTS: We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3-7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year). CONCLUSIONS: Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).
19969421 IL-17 mediates articular hypernociception in antigen-induced arthritis in mice. 2010 Feb IL-17 is an important cytokine in the physiopathology of rheumatoid arthritis (RA). However, its participation in the genesis of nociception during RA remains undetermined. In this study, we evaluated the role of IL-17 in the genesis of articular nociception in a model of antigen (mBSA)-induced arthritis. We found that mBSA challenge in the femur-tibial joint of immunized mice induced a dose- and time-dependent mechanical hypernociception. The local IL-17 concentration within the mBSA-injected joints increased significantly over time. Moreover, co-treatment of mBSA challenged mice with an antibody against IL-17 inhibited hypernociception and neutrophil recruitment. In agreement, intraarticular injection of IL-17 induced hypernociception and neutrophil migration, which were reduced by the pre-treatment with fucoidin, a leukocyte adhesion inhibitor. The hypernociceptive effect of IL-17 was also reduced in TNFR1(-/-) mice and by pre-treatment with infliximab (anti-TNF antibody), a CXCR1/2 antagonist or by an IL-1 receptor antagonist. Consistent with these findings, we found that IL-17 injection into joints increased the production of TNF-alpha, IL-1beta and CXCL1/KC. Treatment with doxycycline (non-specific MMPs inhibitor), bosentan (ET(A)/ET(B) antagonist), indomethacin (COX inhibitor) or guanethidine (sympathetic blocker) inhibited IL-17-induced hypernociception. IL-17 injection also increased PGE(2) production, MMP-9 activity and COX-2, MMP-9 and PPET-1 mRNA expression in synovial membrane. These results suggest that IL-17 is a novel pro-nociceptive cytokine in mBSA-induced arthritis, whose effect depends on both neutrophil migration and various pro-inflammatory mediators, as TNF-alpha, IL-1beta, CXCR1/2 chemokines ligands, MMPs, endothelins, prostaglandins and sympathetic amines. Therefore, it is reasonable to propose IL-17 targeting therapies to control this important RA symptom.
21142618 Recommendations for an update of 2003 European regulatory requirements for registration of 2011 Feb Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.
20210869 Moderators of the negative effects of catastrophizing in arthritis. 2010 Apr OBJECTIVES: Pain is among the most frequently reported, bothersome, and disabling symptoms described by patients with rheumatoid arthritis (RA), and the experience of pain is partially shaped by catastrophizing, a set of cognitive and emotional pain-related processes. However, other variables may moderate catastrophizing's influence on the experience of pain. In this study, we investigated a variety of factors that might buffer or magnify catastrophizing's deleterious consequences among patients with RA. METHODS: A total of 185 RA patients were surveyed to determine levels of catastrophizing, pain, general psychological distress, and physical functioning. RESULTS: Catastrophizing was associated with increased pain severity and psychological distress, and with poorer physical functioning. Some of these relationships were significantly moderated by education and social functioning; among RA patients with above-average social functioning and a college education, minimal relationships of catastrophizing with pain and distress symptoms were observed, while these associations were highly significant (Ps < 0.001) among patients with lower levels of education or social functioning. CONCLUSIONS: Collectively, educational achievement and positive social interactions may protect against some of the deleterious effects of catastrophizing. The design of future interventions to reduce catastrophizing or ameliorate its impact on pain outcomes may benefit from further study of these subgroups of patients.
18628282 Thymic function in juvenile idiopathic arthritis. 2009 Jun OBJECTIVE: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. METHODS: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alphaTREC/SigmabetaTREC ratio. Lastly, regulatory T cells (T(Reg)) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. RESULTS: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. CONCLUSIONS: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA" suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.
20303461 Failure of the hinge mechanism in total elbow arthroplasty. 2010 Apr HYPOTHESIS: Total elbow arthroplasty (TEA) has become an accepted means of dealing with intractable elbow arthritis. The Coonrad-Morrey elbow prosthesis has become the workhorse for management of elbow arthropathy. Its successful initial use in rheumatoid patients has evolved, as has its design, to allow use in osteoarthritic patients and patients with posttraumatic arthritis. More active patients with elbow arthropathy are also treated using TEA. Prior design flaws led to central bushing failure and resulted in a redesign of the implant. However, the newer design has been noted to demonstrate a new mode of failure that appears to be more prevalent in active patients with osteoarthritis and posttraumatic arthritis. The authors hypothesize that the mechanical properties of the second generation hinge mechanism are inadequate to resist the high stresses placed upon it by some active patients treated for osteo- and post-traumatic arthritis. MATERIALS AND METHODS: Since 2000, 2 senior surgeons at Cleveland Clinic performed 82 TEAs, 64 in osteoarthritic or posttraumatic patients. Outcomes are reviewed. RESULTS: Five patients demonstrated failure of the central locking and bushing components, with instability and dissociation requiring revision surgery. Two of these patients had secondary failure and required repeat revision using a more substantial central axis with lock washer and set screw. DISCUSSION: The mode of failure and radiographic and clinical findings demonstrate that younger patients with a more active lifestyle are at risk for central axis and bushing failure. It is recommended that younger, more active patients be monitored indefinitely at 6-month intervals and counseled about the risk of potential failure and the need to limit forces across the reconstructed elbow. RESULTS: These failures indicate the need for alternative designs in younger, active patients.
21086111 [Endoprosthesis for the fractured elbow: uni- and bicompartmental alloarthroplasty of the 2010 Dec Posttraumatic arthrosis or rheumatoid arthritis located at the elbow, in particular at the humero-ulnar joint will probably not occur in increasing numbers in the future due to new antirheumatic medications and modern implants. However, the demographic development with an increase of the geriatric population and the typical physical changes is evident. Due to osteoporosis with a resulting poor bone quality severe fracture patterns may occur at the site of the distal humerus after a simple collapse. The usual surgical aim consisting of an exact anatomic reduction may be impossible to achieve by applying the standard operative treatment. Several studies have proven that a prosthetic replacement of such a severely damaged elbow is a viable solution for elderly people. A mobile, pain-free and stable elbow joint promotes a fast recovery of the patient with a quick return to former activities. Nevertheless, elbow prostheses cannot withstand great strains and the surgeon has to identify those fractures which require a prosthetic replacement. The surgical implantation procedure requires an adequate knowledge of both elbow anatomy and prosthetic options.
20970225 [Azathioprine-associated severe myelosuppression: indication of routine determination of t 2011 Jun INTRODUCTION: Myelotoxicity is a well-known adverse effect of azathioprine, leading mainly to leukopenia. Other azathioprine associated hematological adverse effects are uncommon. CASE REPORT: We report a 49-year-old woman with rheumatoid arthritis and acquired hemophilia, who presented a severe myelosuppression occurring 3 weeks after an increase of her azathioprine regimen (at a daily dose of 150 mg). The patient had a heterozygous mutation of the thiopurine S-methyltransferase gene (TPMT*3A). Azathioprine therapy was discontinued and she recovered at 3 weeks. The patient had no relapse of pancytopenia after a 1 year follow-up. CONCLUSION: Routine measurement of TPMT activity or determination of TPMT variant allele may be useful tests, in order to identify the subgroup of patients who are at risk to develop azathioprine induced severe myelosuppression.
22870444 Risk factors for coronary heart disease in connective tissue diseases. 2010 Jun Atherosclerosis and cardiovascular disease risk is enhanced in certain connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis and antiphospholipid syndrome. The reason for this accelerated process is likely to be multifactorial. Traditional risk factors are more prevalent in some of these patient groups compared with the general population (e.g. smoking in RA and hypertension in SLE). However, these factors do not fully explain that enhanced risk. Chronic inflammation associated with these disorders as well as some specific autoantibodies have been shown to contribute to this increased risk although their role remains controversial. The role of therapies is unclear and while steroids may exacerbate metabolic risk factors, the anti-inflammatory effects of traditional and more novel biological therapies may reduce overall cardiovascular risk in these populations. We recommend proactive screening for modifiable cardiovascular risk factors in patients with these conditions.
20074481 Mixed panniculitis responding to cyclosporin-A with a 12-month follow-up: a case report. 2009 Oct Panniculitides represent a heterogeneous group of inflammatory diseases involving subcutaneous fat. Subcutaneous fat is normally organized into adipose cells, adipocytes, and septa of connective tissue. The inflammation involving such tissues can be more represented in septa (septal panniculitis) or in lobules (lobular panniculitis) or be equally distributed in both (mixed panniculitis). A bioptical study is necessary in order to discern between different forms. Vascular involvement is also different in such diseases, as it can interest arteries, or veins, or both. Different grades of fat necrosis can also be observed, such as adipocytes without nuclei, lipophagic necrosis, liquefactive fat necrosis, microcystic fat necrosis, ischaemic fat necrosis. Panniculitis can be idiopathic or secondary to other diseases such as systemic sclerosis, rheumatoid arthritis, systemic erithematous lupus and many others. Therapies usually vary on the single patient but the general orientation leads to the use of immunosuppressive drugs such as thalidomide, corticosteroids, cyclosporin-A, hydroxychloroquine and cyclophosphamide. We report a case of a 19-year-old female affected by primary mixed panniculitis, associated with fever and deep asthenia, that resolved in a few weeks and was maintained with oral cyclosporin-A.
20051652 Prostaglandin E2, an immunoactivator. 2010 Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn's disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E(2) is the most ubiquitously produced PG with various actions. PGE(2) has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE(2) has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE(2) facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE(2) can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE(2) functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs.
20042314 Effects of tobacco smoke on immunity, inflammation and autoimmunity. 2010 May Smoking is a central factor in many pathological conditions. Its role in neoplasm, lung and cardiovascular diseases has been well established for years. However it is less acknowledged the cigarette smoking affects both the innate and adoptive immune arms. Cigarette smoke was shown to augment the production of numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8 GM-CSF and to decrease the levels of anti-inflammatory cytokines such as IL-10. Tobacco smoke via multiple mechanisms leads to elevated IgE concentrations and to the subsequent development of atopic diseases and asthma. Cigarette smoke has also been shown activate in many ways macrophage and dendritic cell activity. While it is better evident how cigarette smoke evokes airway diseases more mechanisms are being revealed linking this social hazard to autoimmune disorders, for instance via the production of antibodies recognizing citrullinated proteins in rheumatoid arthritis or by the elevation of anti-dsDNA titers in systemic lupus erythematosus. The current review underlines the importance of smoking prevention and eradication not only in respiratory disorders but also in autoimmune conditions as well.
19577563 Evaluation of the impacts of antibiotic drugs on PON 1; a major bioscavenger against cardi 2009 Sep 1 Paraoxonase 1 (PON1) is an antiatherogenic enzyme which is also an organophosphate hydrolyzer. It has crucial roles in detoxification of highly toxic substances and protecting LDL against oxidation. Decrease in the levels of this enzyme is a great risk for the patients with cardiovascular diseases, diabetes mellitus, chronic renal failure, rheumatoid arthritis, hyperthyroidism, and age-related macular degeneration. Therefore, inhibitors and activators of PON1 must be well-characterized, and drug studies would be a good starting point in this regard. Moreover, purification of PON1 has been a challenge for scientists due to its tight association with HDL. Here we report the purification of human serum PON1 using very simple methods and investigation of the interactions between the enzyme and some commonly used antibiotics. We purified PON1 from human serum with a high specific activity, and used the pure enzyme for inhibition studies. We observed that some antibiotics inhibit the enzyme at very low doses while some are efficient at higher doses. The antibiotics exhibited different inhibition mechanisms. We concluded that usage of these antibiotics would be very dangerous in some cases.
19519592 Pharmacological modulation of Th17. 2009 Jun Recently, a third subset of Th17 cells has been described. This T helper subset induces the release of chemokines and growth factors and causes neutrophil accumulation in several mammalian organs. Pharmacological intervention blocking Th17 generation as well as IL-17 signaling might prove useful in a variety of diseases including asthma, chronic obstructive pulmonary disease, Crohn's disease, cystic fibrosis, multiple sclerosis, psoriatic disease and rheumatoid arthritis. Here, we describe the patents that address a potential pharmacological use of promoting or targeting IL-17.
19377643 Proximal tibial stress fractures associated with primary degenerative knee osteoarthritis. 2009 Mar Tibial stress fractures are not rare--they have been extensively studied in young athletes and soldiers and in elderly people with rheumatoid arthritis, osteoporosis, Paget's disease, pyrophosphate arthropathy, and hyperparathyroidism--but they seldom occur in patients with severe primary degenerative knee osteoarthritis. The etiology, diagnosis, and optimal treatment of these fractures remain a challenge. In this article, we review the English-language literature on the symptoms, diagnosis, treatment options, and final outcomes of these fractures, and we report 2 new cases of proximal tibial stress fractures in elderly women with severe primary degenerative knee osteoarthritis.