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ID PMID Title PublicationDate abstract
21923027 [Causes and managements of acetabular fracture during primary total hip arthroplasty]. 2011 Aug OBJECTIVE: To investigate the causes and managements of acetabular fracture during primary total hip arthroplasty (THA). METHODS: Between May 2005 and July 2008, 9 patients (9 hips) suffered from acetabular fractures during primary THA. There were 1 male and 8 females with an average age of 63.3 years (range, 41-73 years), including 4 cases of developmental dysplasia of the hip, 2 cases of rheumatoid arthritis, 1 case of old femoral neck fracture, 1 case of avascular necrosis of femoral head, and 1 case of ankylosing spondylitis. Three left hips and 6 right hips were involved. The preoperative Harris score was 40.4 +/- 2.9. All the patients underwent cementless THA. Among nine acetabular fractures, 8 fractures were stable (2 anterior wall fractures and 6 posterior wall fractures), which were fixed by additional augmentation screws in 7 cases and accepted no special treatment in 1 case; 1 fracture was unstable (posterior wall fracture with posterior column incomplete fracture), which was treated by bone grafting and additional screws. RESULTS: The postoperative X-ray films showed that the position of the prosthesis were favorable. All incisions healed by first intention without early complication. Nine patients were followed up 1-4 years (mean, 2 years and 7 months). The Harris score was 87.8 +/- 3.9 at last follow-up, showing significant difference when compared with the preoperative score (t = 44.904, P = 0.000). The X-ray films showed fracture healing at 8 weeks. No loosening occurred. CONCLUSION: When primary THA is performed, the preoperative X-ray film should be studied and measured carefully, operation should be accurate and violence should be avoided. The diameter of the acetabular component should be equal to the diameter of a drill or not larger than 2 mm. In patients with severe osteoporosis, the diameter of the acetabular components should be the same diameter as a drill and additional screws are used to fix, or cemented cup is used. Once an acetabular fracture occurs during the primary THA, additional screw or bone grafting with additional screws should be chosen according to the fracture type and stability, and good clinical results can be expected.
21897334 Valproic acid increases susceptibility to endotoxin shock through enhanced release of high 2011 Nov High-mobility group box 1 (HMGB1) is a nuclear factor and a secreted protein. During inflammation, HMGB1 is secreted into the extracellular space where it can interact with the receptor for advanced glycation end products and trigger proinflammatory signals. Extracellular HMGB1 plays a critical role in several inflammatory diseases such as sepsis and rheumatoid arthritis. Valproic acid (VPA) is one of the most frequently prescribed antiepileptic drugs. The present study was undertaken to investigate the effect of VPA on secretion of HMGB1 in systemic inflammatory responses induced by lipopolysaccharide. Pretreatment with VPA increased the susceptibility of mice to lipopolysaccharide in endotoxemia. Valproic acid induced HMGB1 release and nuclear factor κB activation in RAW-blue cells. Valproic acid promoted the phosphorylation of ERK1/2 but not that of p38 or JNK. The MEK1/2 inhibitor PD98059 also suppressed HMGB1 release and activation of nuclear factor κB induced by VPA. Valproic acid induced expression of γ-aminobutyric acid receptors in macrophages, and picrotoxin, a γ-aminobutyric acid A receptor antagonist, inhibited the VPA-activated phosphorylation of ERK and VPA-induced HMGB1 release. These results suggest that VPA may exacerbate innate immune responses to endotoxin through enhanced release of HMGB1.
27027051 MEDIUM-TERM ASSESSMENT OF TOTAL KNEE ARTHROPLASTY WITH IMPLANT MADE IN BRAZIL. 2011 Sep OBJECTIVE: This study assessed 47 patients who underwent total knee arthroplasty (TKA) with implants manufactured in Brazil, with a mean follow-up of five years. METHODS: This was a retrospective study at Santa Casa de Misericordia Hospital in Rio de Janeiro, from January 1993 to December 2002. The sample comprised 47 patients (44 females and three males) who underwent TKA, totaling 58 knees. The patients' ages ranged from 46 to 83 years. A diagnosis of osteoarthritis or rheumatic disease was confirmed in all the patients. RESULTS: In this investigation, all the patients underwent cemented TKA with preservation of the posterior cruciate ligament. The length of follow-up ranged from 5 to 17 years. The functional assessment criterion used was the one of the Hospital for Special Surgery (HSS), and this yielded an average of 87 points after the operation. The radiographic criterion used was the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. We had three cases with a radiolucent line without implant loosening, which were asymptomatic from a clinical standpoint. CONCLUSION: The total knee arthroplasty procedures using an implant made in Brazil were performed by a trained and experienced team. To date, over the clinical follow-up on these patients with knee osteoarthritis or rheumatoid arthritis, the results have been seen to be satisfactory.
21878341 Alterations in anxiety-like behavior following knockout of the uncoupling protein 2 (ucp2) 2011 Nov 7 AIMS: Uncoupling protein 2 (UCP2) is a mitochondrial protein that reduces oxidative stress and has a protective function in chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. UCP2 is strongly expressed in areas implicated in the central regulation of stress and anxiety. Therefore, we compared the neuroendocrine regulation of stress responses, immunity and behavior in UCP2-deficient and wildtype C57BL/6J mice under psychological stress. MAIN METHODS: Stress was induced by social disruption (SDR) and anxiety-like behavior was examined using the elevated plus-maze (EPM). Serum corticosterone was determined by radioimmunoassay and brain neurotransmitter concentrations were analyzed by HPLC of whole brain homogenates. T cell activation and tumor necrosis factor (TNF)-α production of mitogen-activated splenocytes were determined in vitro by flow cytometry staining of CD25, CD69 and CD71 on CD4 cells, and ELISA, respectively. The influence of corticosterone on UCP2 expression of splenocytes was analyzed by Western blot. KEY FINDINGS: At baseline, UCP2-deficient mice were significantly more anxious in the EPM than wildtype mice, and this phenotype was exacerbated after SDR stress. The corticosterone response after SDR+EPM was reduced in UCP2-deficient mice compared to wildtype mice. Corticosterone in turn downregulates UCP2 expression in splenocyte cultures of wildtype mice at physiological concentrations. Dopaminergic and serotonergic turnovers were increased in UCP2-deficient mice after SDR+EPM. While T-helper cell activation-marker expression was reduced, TNF-α production was increased in UCP2-deficient mice after SDR+EPM. SIGNIFICANCE: Our study shows that UCP2 is involved in anxiety-like behavior and modulates neuroendocrine and immune responses after stress.
21755374 Development of the patient-based outcome instrument for foot and ankle: part 2: results fr 2011 Sep BACKGROUND: The Clinical Outcomes Committee of the Japanese Society for Surgery of the Foot (JSSF) has conducted the second Field Survey of the Outcome Instrument for the Foot and Ankle version 2. METHODS: The survey of the Outcome Instrument version 2, which was composed of 43 items, was performed in 313 patients (154 men and 159 women) who had pathological conditions related to the foot and ankle. Optional sports items in the Outcome Instrument version 2 were analyzed in 123 patients. Internal consistency and construct validity of the Outcome Instrument version 2 were assessed. Correlation of the Outcome Instrument version 2 score with Short Form 36 (SF36) and JSSF scores was analyzed to evaluate criterion validity. RESULTS: Both the EFA and CFA demonstrated good alignment of questionnaire items with their intended subscales in most cases. Sports items were not clearly classified into subgroups. Therefore, it seemed reasonable to use those as a set of questions in a single subscale. The present subscales, having similar names as the SF36 subscales, were closely correlated with the respective subscales. In those cases, the magnitude of the correlation coefficient was >0.6 (p < 0.001) except the present subscale called General Health and Well-being. Comparison of the present scores with JSSF evaluation scores showed satisfactory results except in patients with rheumatoid arthritis. CONCLUSIONS: The Outcome Instrument version 2 demonstrated acceptable psychometric performances as outcome measures for patients with pathological conditions related to the foot and ankle. This outcome instrument would be helpful to evaluate patients with foot and/or ankle impairment. However, the analyses of the test-retest reliability and the influence of background factors such as age and gender, etc., on Outcome Instrument version 2 are needed in the third field survey.
21717518 Topical application of two condensed tannins from the root of Rosa multiflora Thunberg for 2011 Oct Recently, the isolation of several condensed tannins from the roots of Rosa multiflora Thunberg, a traditional herbal therapy in oriental medicine for rheumatoid arthritis and scabies, was described. Two of the major condensed tannins - procyanidin B-3 (ProB3) and ent-guibourtinidol-(4β → 6)-catechin (RM-1) - were then applied topically to atopic dermatitis-like skin lesions on NC/Nga mice in order to assess their immunomodulatory properties. Both ProB3 and RM-1 significantly reduced the serum levels of eosinophils, IgE and certain Th2 cytokines (IL-4, 5 and 13) (p < 0.05 or 0.01). Additionally, ProB3 and RM-1 significantly reduced both the mRNA and protein expression of COX-2 and iNOS in mouse skin tissues (p < 0.01). Such results strongly suggest that ProB3 and RM-1 may be useful in the treatment allergic skin conditions, most notably atopic dermatitis.
21652557 p38 mitogen-activated protein kinase pathways in asthma and COPD. 2011 Jun The mitogen-activated protein kinase (MAPK) family includes the p38 kinases, which consist of highly conserved proline-directed serine-threonine protein kinases that are activated in response to inflammatory signals. Of the four isoforms, p38α is the most abundant in inflammatory cells and has been the most studied through mainly the availability of small molecule inhibitors. The p38 substrates include transcription factors; other protein kinases, which in turn phosphorylate transcription factors; cytoskeletal proteins and translational components; and other enzymes. Both asthma and COPD are characterized by chronic airflow obstruction, airway and lung remodeling, and chronic inflammation. p38 is involved in the inflammatory responses induced by cigarette smoke exposure, endotoxin, and oxidative stress through activation and release of proinflammatory cytokines/chemokines, posttranslational regulation of these genes, and activation of inflammatory cell migration. Inhibition of p38 MAPK prevented allergen-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness, effects that may partly result from p38 activation on eosinophil apoptosis and on airway smooth muscle cell production of cytokines/chemokines. In addition, p38 regulates the augmented contractile response induced by oxidative stress. The activation of p38 observed in epithelial cells and macrophages also may underlie corticosteroid insensitivity of severe asthma and COPD. Therefore, p38 inhibitors present a potential attractive treatment of these conditions. Second-generation p38 inhibitors have been disappointing in the treatment of rheumatoid arthritis. In two 6-week studies in patients with COPD, the results were encouraging. Side effects such as liver toxicity remain a possibility, and whether the beneficial effects of p38 inhibitors are clinically significant and sustained need to be determined.
21445458 Judicialization of access to medicines in Minas Gerais state, Southeastern Brazil. 2011 Jun OBJECTIVE: To analyze the profile of claimants and medicines demanded in lawsuits. METHODS: Descriptive study that examined 827 lawsuits with 1,777 demands of access to medicines in the period between July 2005 and June 2006 in the state of Minas Gerais, Southeastern Brazil. There were examined the type of health care provided to claimants and their attorneyship. The medicines were described based on the following: drug registration at the National Health Surveillance Agency (Anvisa); wheter they were essential medicines; supply in the Brazilian Health System programs; and evidence of drug efficacy. RESULTS: More than 70% of the claimants were provided care in the private health system and 60.3% hired private lawyers. The most common diagnosis of claimants was rheumatoid arthritis (23.1%) and the immunosuppressant agents were the most frequent demand medicines (mainly adalimumab and etanercept). Approximately 5% of the medicines demanded were not registered at Anvisa, 19.6% were included in the Brazilian List of Essential Medicine, 24.3% were included in the High-Cost Drug Program and 53.9% showed consistent evidence of efficacy. Among the medicines that were not available in Brazilian Health System, 79.0% had therapeutic alternatives in drug programs. CONCLUSIONS: The phenomenon of judicialization of health in Brazil can point out failures in the public health system as some medicines demanded are included in its lists. However, it is a barrier for rational drug use and application of the National Drug Policy guidelines, especially when there are demanded medicines with no evidence of efficacy and that are not included in Brazilian Health System standards.
21245206 Therapeutic targeting of B cells for rheumatic autoimmune diseases. 2011 Mar Autoreactive B cells are characterized by their ability to secrete autoantibodies directed against self-peptides. During the last decade, it has become increasingly apparent that B lymphocytes not only produce autoantibodies but also exert important regulatory roles independent of their function as antibody-producing cells. This is especially relevant in the context of autoimmunity, because autoreactive B cells have been shown to possess the ability to activate pathogenic T cells, to produce pro-inflammatory cytokines, and to promote the formation of tertiary lymphoid tissue in target organs. The production of monoclonal antibodies against B-cell-surface molecules has facilitated the characterization of several distinct B lymphocyte subsets. These cell-surface molecules have not only served as useful cell differentiation markers but have also helped to unravel the important biological functions of these cells. Some of these molecules, all of which are expressed on the cell surface, have proven to be effective therapeutic targets. In both animal models and in clinical assays, the efficient elimination of B lymphocytes has been shown to be useful in the treatment of rheumatoid arthritis and other autoimmune diseases. The treatment of most rheumatic autoimmune diseases relies mainly on the use of cytotoxic immunosuppressants and corticosteroids. Although this has resulted in improved disease survival, patients may nonetheless suffer severe adverse events and, in some cases, their relapse rate remains high. The increasing need for safer and more effective drugs along with burgeoning new insights into the pathogenesis of these disorders has fueled interest in biological agents; clinical trials involving the B-cell depletion agent rituximab have been especially promising. This article reviews the current knowledge of B-cell biology and pathogenesis as well as the modern therapeutic approaches for rheumatic autoimmune diseases focusing in particular on the targeting of B-cell-specific surface molecules and on the blocking of B-cell activation and survival.
20809180 Molecular mechanisms by which saturated fatty acids modulate TNF-α expression in mouse ma 2011 Mar Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-α (TNF-α). TNF-α is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 μM of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-α production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-α secretion by the cells. Saturated FAs were potent inducers of TNF-α expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-α.
22538102 [MEDIN implant of the first metatarsophalangeal joint]. 2012 PURPOSE OF THE STUDY: Hemiarthoplasty or total replacement of the first metatarsophalangeal (MTP) joint has been used in orthopaedic surgery for the last 60 year, but good post-operative outcomes have been achieved only in the last ten years. Joint replacement is mainly used in stage 3 and stage 4 hallux rigidus conditions for which arthrodesis is not indicated. The operation on the first MTP joint has its place in the present-day orthopaedics. This study describes anatomical measurements and the development of the first Czech implant (MEDIN Orthopaedics) to replace this joint. MATERIAL AND METHODS: Thirty cadaver specimens were used to develop basic shapes of phalangeal and metatarsal components. A standard technique was used for anatomical dissection of the first MTP joint. Fifteen specimens were cut in the sagittal plane and fifteen in the transverse plane in order to open the intramedullary cavity of the proximal phalanx of the great toe and the first metatarsal bone. The basic shapes of phalangeal and metatarseal components were designed based on the shape of cortical bone of their inner surfaces. Data for the shape, size and scale of articular components were obtained by measurement on 58 dry bone specimens of the first metatarsus and on 30 calibrated X-ray images. In order to adjust the scale and size of components, the final shape and the range of implant size were tested on 50 specimens of dissected lower extremities fixed in formaldehyde, acetone, ethyl-alcohol and glycerol. RESULTS: The new type of a first MTP implant designed by us was based on cone-shaped anchor components coated with hydroxyapatite. The implants can be used in hemiarthroplasty or total joint replacement. The metatarsal insert was designed with a declination angle of 20 degrees to facilitate good dorsiflexion and with a flattening to ensure good function of the sesamoid bones, The phalangeal articular insert was made of either CoCr alloy or low-weight polyethylene for use in hemiarthroplasty and total joint replacement, respectively. DISCUSSION: The new implants are designed for treatment of stage 3 or stage 4 hallux rigidus. We recommend to use hemiarthroplasty or total joint replacement only in the case of first metatarsal head destruction or severe joint destruction due to rheumatoid arthritis. CONCLUSIONS: Our anatomical study of the first MTP joint, proximal phalanx of the great toe and first metatarsal bone was used to design the first Czech implant of this joint.
31644151 Monoclonal Antibodies. 2012 Monoclonal antibodies are antibodies that have a high degree of specificity (mono-specificity) for an antigen or epitope. Monoclonal antibodies are typically derived from a clonal expansion of antibody producing malignant human plasma cells. The initial monoclonal antibodies were created by fusing spleen cells from an immunized mouse with human or mouse myeloma cells (malignant self-perpetuating antibody producing cells), and selecting out and cloning the hybrid cells (hybridomas) that produced the desired antibody reactivity. These initial monoclonal products were mouse antibodies and were very valuable in laboratory and animal research and diagnostic assays, but were problematic as therapeutic agents because of immune reactions to the foreign mouse protein. Subsequently, production of chimeric mouse-human monoclonal antibodies and means of further “humanizing” them and producing fully human recombinant monoclonal antibodies were developed. The conventions used in nomenclature of monoclonal antibodies indicate whether they are mouse (-omab), chimeric (-ximab), humanized (-zumab) or fully human (-umab). Monoclonal antibodies have broad clinical and experimental medical uses. Many of the initial monoclonal antibodies used in clinical medicine were immunomodulatory agents with activity against specific immune cells, such as CD4 or CD3 lymphocytes, which are important in the pathogenesis of rejection after solid organ transplantation. Subsequently, monoclonal antibodies were prepared against specific cytokines (anti-cytokines), which were believed to play a role in cell and tissue damage in immunologically mediated diseases such as rheumatoid arthritis, alkylosing spondylitis, inflammatory bowel disease, multiple sclerosis and psoriasis, among others. In addition, therapeutic monoclonal antibodies were developed, aimed at blocking or inhibiting the activity of specific enzymes, cell surface transporters or signaling molecules and have been used in cancer chemotherapy and to treat severe viral infections. Use of monoclonal antibodies is currently broadening to therapy of other severe, nonmalignant conditions including asthma, atopic dermatitis, migraine headaches, hypercholesterolemia, osteoporosis and viral or bacterial infections. Thus, the therapeutic monoclonal antibodies do not fall into a single class and have broad therapeutic uses. As of 2018, more than 60 therapeutic monoclonal antibodies are approved and in use in the United States. Monoclonal antibodies are generally well tolerated. Because they are large proteins (typically 150-200,000 daltons in size) they require parenteral, often intravenous, administration. Circulating proteins are metabolized by many cells, but particularly by hepatocytes. Proteins undergo hepatic uptake by endocytosis and are either degraded or recycled to the cell surface for secretion. The hepatic metabolism of antibodies often determines their half-life. Proteins are broken down by cellular proteases into small peptides and amino acids that can used to synthesize other proteins. Metabolism of proteins does not generate toxic intermediates and, therefore, monoclonal antibodies are unlikely to induce drug induced liver injury via production of toxic metabolites. On the other hand, the peptides that are generated by the metabolism of the exogenously administered protein may ultimately be presented as foreign epitopes and generate an immune response. In addition, the primary effect of the monoclonal antibody may generate a response, either immune or otherwise, that leads to an immune mediate hepatic injury. Finally, monoclonal antibodies that suppress the immune system may cause reactivation of latent infections, including tuberculosis and hepatitis B.
23251857 Eszopiclone treatment for insomnia: effect size comparisons in patients with primary insom 2012 OBJECTIVE: The purpose of this post hoc analysis was to compare the treatment effect size of eszopiclone 3 mg for insomnia in patients with a diagnosis of primary insomnia and in several of the psychiatric and medical conditions that are most commonly comorbid with insomnia. METHOD: Data were analyzed from 5 large, multicenter, randomized, double-blind, placebo-controlled studies of adult outpatients of at least 1 month duration published between 2006 and 2009. Diary-derived indices of sleep and daytime functioning and the Insomnia Severity Index were compared for patients with primary insomnia (DSM-IV-TR criteria, n = 828) and for those with insomnia comorbid with major depressive disorder (MDD, DSM-IV-TR criteria, n = 545), generalized anxiety disorder (GAD, DSM-IV-TR criteria, n = 595), perimenopause/postmenopause (Stages of Reproductive Aging Workshop criteria, n = 410), and rheumatoid arthritis (American College of Rheumatology criteria, n = 153). Cohen d effect sizes were calculated for each individual study as the between-treatment difference score divided by the pooled standard deviation. RESULTS: Effect sizes ranged from 0.40 to 0.69 (small-medium) as early as week 1 and were maintained at 0.26-0.63 at week 4 for sleep latency, wake time after sleep onset, and total sleep time. Sleep latency and total sleep time effect sizes increased from week 1 to week 4 in the primary insomnia group. At week 4, effect sizes on all 3 parameters and the Insomnia Severity Index tended to be highest for the primary insomnia patients and tended to be lowest for patients with comorbid GAD and MDD. The effect sizes for daytime functioning were small for all insomnia patient groups. CONCLUSIONS: Eszopiclone 3 mg is an effective treatment for insomnia across 5 clinically diverse patient populations; however, magnitude of effect is mediated by underlying comorbidity and their treatments, with largest measures of effect seen in primary insomnia and lowest in MDD and GAD. These consistent results, and the fact that clinical trials were conducted in patients being treated as appropriate for their comorbid clinical conditions, support the results' real-world generalizability and utility to clinical practice.
23247975 Identification of cytomegalovirus and human herpesvirus-6 DNA in a patient with corneal en 2013 Mar PURPOSE: To report the case of a patient with unilateral corneal endotheliitis in which both cytomegalovirus (CMV) and human herpesvirus-6 (HHV6) DNA was identified in the aqueous humor. CASE: A 67-year-old man with corneal endotheliitis OD was referred to us for decreased visual acuity. Local corneal stromal edema, pigmented keratic precipitates, a coin-shaped lesion and minimal anterior chamber reaction were observed by slit-lamp biomicroscopy. Cells with owl's eye appearance in the endothelial cell layer were observed by in vivo laser confocal microscopy. The patient had rheumatoid arthritis, which was treated by oral prednisolone and intravenous abatacept. Polymerase chain reaction analysis of aqueous humor samples detected both CMV and HHV6 DNA, but not other HHVs. Treatment with topical ganciclovir and systemic valganciclovir resulted in a clear cornea. CONCLUSIONS: A patient with corneal endotheliitis had both CMV and HHV6 DNA identified in the aqueous humor. Although both viruses were identified in this case, clinical manifestations resembled CMV corneal endotheliitis, and it was unclear whether HHV6 could affect the clinical course. Systemic abatacept and corticosteroid therapy might play a positive role in cases with both CMV and HHV6 DNA in this corneal endotheliitis.
23238666 High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory d 2013 May Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75-325 mg/day) in most (≥95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this "high on treatment platelet reactivity" are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal anti-inflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain.
23145208 Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis rel 2012 AIM: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. METHODS: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. RESULTS: In CCl(4)-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in F0 (632 ng/mL ±75, p<0.05), 54% in F1 (597 ng/mL ±41.3, p<0.05) and 62% in F2 (628 ng/mL ±59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in F0 (339 ±12 ng/mL, P<0.05), 23.8% in F1 (348 ±12 ng/mL, P<0.05) and 28.8% in F2 (362 ±25 P<0.05). CONCLUSION: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.
23136556 Role of IL-6 in asthma and other inflammatory pulmonary diseases. 2012 The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality. Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease. Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected. IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung. However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD. IL-6 may therefore be a germane target for treatment of these and other chronic lung disease. Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases.
22905341 Granulocyte Macrophage Colony Stimulating Factor Treatment is Associated with Improved Cog 2012 BACKGROUND: Endogenous Granulocyte Macrophage Colony Stimulating Factor (GMCSF) is released in rheumatoid arthritis patients, who are largely protected from Alzheimer's disease (AD). Introducing exogenous GMCSF into an AD mouse model reduced amyloid deposition by 55% and restored normal cognition. No published studies have examined exogenous GMCSF and cognitive functioning in humans. OBJECTIVES/DESIGN: The goal of the current study was to examine the association between receipt of GMCSF and cognitive functioning in patients receiving colony stimulating factors as part of routine supportive care for hematopoietic cell transplantation (HCT). SETTING AND PARTICIPANTS: Archived neuropsychological data were examined from a longitudinal study of cognitive functioning in 95 patients receiving HCT at the Moffitt Cancer Center. INTERVENTION: Receipt of GMCSF and/or Granulocyte Colony Stimulating Factor (GCSF) was ascertained through patient billing records. MEASUREMENTS: Patients were assessed with a battery of neuropsychological tests prior to transplant and 6 and 12 months post-transplant. RESULTS: Patients treated with GMCSF and GCSF (n=19) showed significantly greater improvement in total neuropsychological functioning (TNP) at 6 months than patients treated with GCSF only (n=76) (p=.04). There was no group difference in TNP at 12 months (p=.24). Improvement in TNP from baseline to 6 months post-HCT was significant in the GMCSF+GCSF group (p=.01) but not the GCSF only group (p=.33). Improvement in TNP from baseline to 12 months post-HCT was significant in both groups (ps<.01). CONCLUSION: Preliminary data from this study of humans receiving colony stimulating factors suggest that receipt of GMCSF+GCSF was associated with greater cognitive improvement than GCSF alone. Randomized controlled trials of the effects of GMCSF on cognitive functioning in humans are warranted and underway to confirm these findings.
22713918 Fabrication of electrolytic cell for online post-column electrochemical derivatization in 2012 Jul 20 An electrolytic cell (EC), composed of two ruthenium-plated titanium electrodes separated by cation-exchange membranes, was fabricated and evaluated for online postcolumn derivatization in ion chromatography (IC). Folic acid (FA) and methotrexate (MTX) were preliminarily used as prototype analytes to test the performance of EC. After separation by an anion exchange column, FA and MTX, which emit very weak fluorescence when excited, were electrochemically oxidized online in the anode chamber of the EC. The compounds with strong fluorescence, which are oxidation products, were detected by the fluorescence detector. The phosphate buffer solution (100 mM KH(2)PO(4)) served as an optimal eluent for anion exchange chromatographic separation and a suitable supporting electrolyte for electro-oxidation, leading to ideal compatibility between IC separation and the postcolumn electrochemical derivatization. For the presently proposed method, the linear ranges were from 0.01 mg L(-1) to 5 mg L(-1) for both FA and MTX. The detection limits of FA and MTX were 1.8 and 2.1 μg L(-1), and the relative standard deviations (RSD, n=7) were 2.9% and 3.6%, respectively. The method was applied for the simultaneous determination of FA and MTX in the plasma of patients being treated for rheumatoid arthritis. The determination of MTX in the urine of the patients of diffuse large B cell lymphoma was also demonstrated.
22684631 Critical review: vegetables and fruit in the prevention of chronic diseases. 2012 Sep BACKGROUND: Vegetables and fruit provide a significant part of human nutrition, as they are important sources of nutrients, dietary fibre, and phytochemicals. However, it is uncertain whether the risk of certain chronic diseases can be reduced by increased consumption of vegetables or fruit by the general public, and what strength of evidence has to be allocated to such an association. METHODS: Therefore, a comprehensive analysis of the studies available in the literature and the respective study results has been performed and evaluated regarding obesity, type 2 diabetes mellitus, hypertension, coronary heart disease (CHD), stroke, cancer, chronic inflammatory bowel disease (IBD), rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD), asthma, osteoporosis, eye diseases, and dementia. For judgement, the strength of evidence for a risk association, the level of evidence, and the number of studies were considered, the quality of the studies and their estimated relevance based on study design and size. RESULTS: For hypertension, CHD, and stroke, there is convincing evidence that increasing the consumption of vegetables and fruit reduces the risk of disease. There is probable evidence that the risk of cancer in general is inversely associated with the consumption of vegetables and fruit. In addition, there is possible evidence that an increased consumption of vegetables and fruit may prevent body weight gain. As overweight is the most important risk factor for type 2 diabetes mellitus, an increased consumption of vegetables and fruit therefore might indirectly reduces the incidence of type 2 diabetes mellitus. Independent of overweight, there is probable evidence that there is no influence of increased consumption on the risk of type 2 diabetes mellitus. There is possible evidence that increasing the consumption of vegetables and fruit lowers the risk of certain eye diseases, dementia and the risk of osteoporosis. Likewise, current data on asthma, COPD, and RA indicate that an increase in vegetable and fruit consumption may contribute to the prevention of these diseases. For IBD, glaucoma, and diabetic retinopathy, there was insufficient evidence regarding an association with the consumption of vegetables and fruit. CONCLUSIONS: This critical review on the associations between the intake of vegetables and fruit and the risk of several chronic diseases shows that a high daily intake of these foods promotes health. Therefore, from a scientific point of view, national campaigns to increase vegetable and fruit consumption are justified. The promotion of vegetable and fruit consumption by nutrition and health policies is a preferable strategy to decrease the burden of several chronic diseases in Western societies.