Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Impact of the Recent Measurements of the Top-Quark and W-Boson Masses on Electroweak Precision Fits.

We assess the impact of the very recent measurement of the top-quark mass by the CMS Collaboration on the fit of electroweak data in the standard model and beyond, with particular emphasis on the prediction for the mass of the W boson. We then compare this prediction with the average of the corresponding experimental measurements including the new measurement by the CDF Collaboration, and discuss its compatibility in the standard model, in new physics models with oblique corrections, and in the dimension-six standard model effective field theory. Finally, we present the updated global fit to electroweak precision data in these models.

Spread of mcr-1-carrying Enterobacteriaceae in sewage water from Spain.

Objectives: The mobile colistin resistance gene mcr-1 has been identified worldwide in human and animal sources, while its occurrence in the environment is still largely unknown. The aim of this study was to investigate the presence of mcr-1 -harbouring Enterobacteriaceae in water samples obtained from rivers and waste water treatment plants in the area of Barcelona, Spain. Methods: The presence of mcr-1 was detected by PCR. Bacterial identification was performed via MALDI-TOF MS. Resistance to colistin was determined by a broth dilution method. The epidemiological relationship between the positive isolates was assessed with PFGE and ST was determined by MLST. Plasmid characterization was performed by transformation experiments, antimicrobial susceptibility testing and incompatibility group PCR. Results: Thirty MDR isolates bearing mcr-1 , 29 Escherichia coli (ST632 and ST479) and 1 Klebsiella pneumoniae (ST526), were identified in sewage from two different waste water treatment plants, whereas the gene was not found in river water. All isolates, including the K. pneumoniae , harboured bla CTX-M-55 and bla TEM-1 . mcr-1 was in all cases associated with an IncI2 plasmid, which only conferred resistance to colistin. mcr-1 was harboured by two predominant E. coli clones that were found in both waste water treatment plants. Conclusions: This study showed a high occurrence of mcr-1 in the sewage of Barcelona, mainly due to the dissemination of two E. coli pulsotypes that are circulating in the population. The presence of mcr-1 in the environment is a cause for concern, and suggests high prevalence of mcr-1 in the community.

[Anaphylaxis and allergic reactions during surgery and medical procedures]. / Anafilaxias y reacciones alérgicas durante cirugías y procedimientos médicos.

Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the responsible drugs include neuromuscular blocking agents, latex, or antibiotics. The frequency and etiology of systemic allergic reactions in other medical procedures are largely unknown. The identification of responsible drugs of anaphylaxis is a complex task, requiring testing of all medications and substances used during surgery. We describe our experience in a retrospective study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in endoscopic studies and one in a trans-vaginal ultrasound. The remaining two subjects, one in a trans-vaginal ultrasound and another during a dental procedure had a systemic allergic reaction. We studied all patients with all medications administered during the procedures, including latex and detergents and disinfectants. Three surgeries had to be suspended at induction of anesthesia, five were stopped incomplete and two were completed. Both patients that presented a reaction during endoscopy required intensive care unit admission and the rest were observed in a Hospital. The responsible drugs during surgery anaphylaxis were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho-phthalaldehyde (OPA) was identified during endoscopic studies; latex was responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure. The aim of the present article is to review our experience studying allergic systemic reactions and anaphylaxis during general anesthesia and medical procedures, emphasizing the severity of these reactions and the need for causative drug identification.

What is the likelihood of colorectal cancer when surgery for ulcerative-colitis-associated dysplasia is deferred?

AIM: Surgery aims to prevent cancer-related morbidity for patients with ulcerative colitis (UC) associated dysplasia. The literature varies widely regarding the likelihood of dysplastic progression to higher grades of dysplasia or cancer. The aim of this study was to characterize the likelihood of the development of colorectal cancer (CRC) of patients with UC-associated dysplasia who chose to defer surgery. METHOD: A retrospective review was carried out of patients undergoing surgery for UC at the Mayo Clinic, who were diagnosed to have dysplasia between August 1993 and July 2012. The relationships between grade of dysplasia, time to surgery and the detection of unsuspected carcinoma were investigated. RESULTS: In all, 175 patients underwent surgery at a median of 4.9 (interquartile range 2.5-8.9) months after a diagnosis of dysplasia. Their median age was 52 (interquartile range 43-59) years. An initial diagnosis of indeterminate dysplasia was not associated with CRC [0/23; 17.7 (8.1-29.6) months]. Thirty-six patients who had an initial diagnosis of dysplasia progressed from indeterminate to low-grade dysplasia [24.2 (11.0-30.4) months]. Low-grade dysplasia was associated with a 2% (1/56; T2N0M0) risk of CRC when present in random surveillance biopsies and a 3% (2/61; T1N0M0, T4N0M0) risk if detected in endoscopically visible lesions [7.4 (5.2-33.3) months]. Eighteen patients progressed from indeterminate to high-grade dysplasia [19.1 (9.2-133.9) months]. Seventeen patients progressed from low to high-grade dysplasia [11.0 (5.8-30.1) months]. None of the patients with high-grade dysplasia (0/35) progressed to CRC [4.5 (1.7-9.9) months]. CONCLUSION: Dysplasia was associated with a low incidence of node negative CRC if surgery was deferred for up to 5 years. These findings may help inform the decision-making process for asymptomatic patients who are having to decide between intensive surveillance or surgery for UC-associated dysplasia.

[Relapses in inflammatory myopathies]. / Miopatías inflamatorias con evolución recidivante.

Most studies about treatment of inflammatory myopathies consist of cross-sectional analyses that do not assess long-term efficacy. In the present study we describe the follow-up of seven patients with inflammatory myopathies, 5 polymyositis and 2 dermatomyositis. We describe their clinical features, follow-up, muscle enzyme levels, and treatment responses. We define the latter as treatment cycles, every one of which end when steroid doses need to be increased or a new immunosuppressive drug has to be added because of clinical worsening or sustained increases in muscle enzyme levels. Treatment can cause remission, partially control, or fail in achieving myositis improvement when it normalizes, stabilizes, or does not affect muscle enzymes or clinical features, respectively. We analyzed 20 cycles, in which remission was achieved in 14 cases, partial control in 5 instances, and treatment failure in one case. Remission occurred after an average of 139 ± 98 days, whereas partial control took place in 160 ± 100 days. Except in one case, all treatment cycles controlled or remitted the symptoms. However, in all patients the illness recurred with time.

Epidemiology of angioedema without wheals in an allergy and immunology center.

We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.

[Rituximab and hypogammaglobulinemia]. / Rituximab e hipogammaglobulinemia.

Rituximab, a chimeric monoclonal antibody against CD20, induces the depletion of B lymphocytes. It is used for the treatment of lymphoproliferative and autoimmune diseases. Antibody immunodeficiency associated to RTX treatment is a new motif for consultation to our service. We decided to study those patients that having been treated with RTX, consulted for hypogammaglobulinemia or recurrent infections between November 2010 and December 2014. We evaluated eight patients, seven female and one male. The average follow up time was 19.3±18.8 months, range 1 to 54, median 13. Three had a normal electrophoretic proteinogram before receiving RTX, three had hypogammaglobulinemia and in two data was not available. None of them had a quantitative determination of immunoglobulins before receiving RTX. Four received RTX as a treatment of non Hodking lymphoma, two as a treatment of chronic lymphocytic leukemia, one for immune thrombocytopenic purpura and other for microscopic polyangiitis. Six were diagnosed with hypogammaglobulinemia and one with combined IgM, IgA and IgG2 deficiency. Five presented infections, four of them with good response to intravenous immunoglobulin. RTX related antibody deficiency consultations are increasing. It is important to determine the immunoglobulin levels previously to RTX use in order to establish an etiologic relationship with RTX and a quick diagnosis of antibody deficiency. The substitutive treatment with gammaglobulin seems to be useful in patients with severe or recurrent infections.

Behaviour-related DRD4 polymorphisms in invasive bird populations.

It has been suggested that individual behavioural traits influence the potential to successfully colonize new areas. Identifying the genetic basis of behavioural variation in invasive species thus represents an important step towards understanding the evolutionary potential of the invader. Here, we sequenced a candidate region for neophilic/neophobic and activity behaviour - the complete exon 3 of the DRD4 gene - in 100 Yellow-crowned bishops (Euplectes afer) from two invasive populations in Spain and Portugal. The same birds were scored twice for activity behaviour while exposed to novel objects (battery or slice of apple) in captivity. Response to novel objects was repeatable (r = 0.41) within individuals. We identified two synonymous DRD4 SNPs that explained on average between 11% and 15% of the phenotypic variance in both populations, indicating a clear genetic component to the neophilic/neophobic/activity personality axis in this species. This consistently high estimated effect size was mainly due to the repeated measurement design, which excludes part of the within-individual nongenetic variance in the response to different novel objects. We suggest that the alternative alleles of these SNPs are likely introduced from the original population and maintained by weak or antagonistic selection during different stages of the invasion process. The identified genetic variants have not only the potential to serve as genetic markers of the neophobic/neophilic/activity personality axis, but may also help to understand the evolution of behaviour in these invasive bird populations.

The number of life-history stages does not influence the androgen responsiveness to male-male interactions: sedentary and migratory black redstarts (Phoenicurus ochruros) do not elevate testosterone in response to simulated territorial intrusions.

High plasma levels of testosterone at the beginning of the breeding season adjust male physiology for mating and promote territorial behavior in birds. Conversely intra-sexual competition may elicit a temporary increase in circulating testosterone. Male black redstarts (Phoenicurus ochruros) from migratory populations show the expected increase in baseline testosterone during early breeding, but circulating testosterone levels do not change in response to male-male interactions. Because sedentary populations express fewer life-history stages they may be more flexible in timing of life-history stages and more responsive to environmental modulation of hormone concentrations. Therefore, we tested whether the androgen responsiveness to male-male interactions differs between migratory (6 life-history stages) and sedentary black redstarts (3 life-history stages) during early breeding, predicting that in contrast to migratory birds, sedentary birds would modulate testosterone in response to simulated territorial intrusions (STI). In contrast to our prediction, sedentary males did not modulate post-capture testosterone levels in response to simulated territorial intrusions. Males of both populations increased testosterone after an injection of gonadotropin releasing hormone (GnRH), demonstrating that they were capable of increasing testosterone. Interestingly, in sedentary males the GnRH injection elicited a higher testosterone response in STI males than in control males. The two populations did not differ in their behavioral response to the STIs, except that sedentary males spent less time close to the decoy. In combination with previous data from black redstarts and other socially monogamous and biparental birds our current study adds to the growing evidence that current theory regarding hormone-behavior relationship needs to be refined.

Deep Learning-Based Estimation of Radiographic Position to Automatically Set Up the X-Ray Prime Factors.

Radiation dose and image quality in radiology are influenced by the X-ray prime factors: KVp, mAs, and source-detector distance. These parameters are set by the X-ray technician prior to the acquisition considering the radiographic position. A wrong setting of these parameters may result in exposure errors, forcing the test to be repeated with the increase of the radiation dose delivered to the patient. This work presents a novel approach based on deep learning that automatically estimates the radiographic position from a photograph captured prior to X-ray exposure, which can then be used to select the optimal prime factors. We created a database using 66 radiographic positions commonly used in clinical settings, prospectively obtained during 2022 from 75 volunteers in two different X-ray facilities. The architecture for radiographic position classification was a lightweight version of ConvNeXt trained with fine-tuning, discriminative learning rates, and a one-cycle policy scheduler. Our resulting model achieved an accuracy of 93.17% for radiographic position classification and increased to 95.58% when considering the correct selection of prime factors, since half of the errors involved positions with the same KVp and mAs values. Most errors occurred for radiographic positions with similar patient pose in the photograph. Results suggest the feasibility of the method to facilitate the acquisition workflow reducing the occurrence of exposure errors while preventing unnecessary radiation dose delivered to patients.

Effects of PTH [1-34] on synoviopathy in an experimental model of osteoarthritis preceded by osteoporosis.

PURPOSE: Synoviopathy contributes to cartilage degradation in osteoarthritis (OA). Intermittent parathyroid hormone (PTH) [1-34] administration inhibits terminal differentiation of human chondrocytes and prevents cartilage damage. We aimed to determine whether PTH [1-34] could modify synovial changes in experimental OA preceded by osteoporosis (OP). METHODS: Twenty osteoporosis (OP) rabbits underwent knee surgery to induce OA. They were administered either saline vehicle or PTH for 10 weeks. Ten healthy rabbits were used as controls. Following sacrifice, synovial changes were assessed by Krenn synovitis score, immunohistochemistry for macrophages (RAM-11), B and T lymphocytes, type I collagen, parathyroid hormone 1 receptor (PTH1R), and anti-proliferating cell nuclear antigen (PCNA). Synovial mRNA levels of Col1A1, IL-1ß, cyclooxygenase 2 (COX-2), matrix-degrading metalloproteinases (MMP-9, MMP-13), and monocyte chemotactic protein-1 (MCP-1), as well as protein expression of PTH1R were also determined. Cartilage damage was analyzed by Mankin score. RESULTS: OPOA + vehicle rabbits showed an increase in synovitis score vs controls (P = 0.003), mainly due to synovial hyperplasia and fibrosis, while PTH reduced these changes (P = 0.017). Mankin and Krenn scores were well correlated in all groups (r = 0.629, P = 0.012). Immunostaining for RAM-11 and B lymphocytes was increased (P ≤ 0.05), whereas PTH1R protein levels tended to be higher in OPOA + vehicle animals vs controls. PTH did not modify RAM-11 staining or PTH1R levels; however, it restored PTH1R localization to the vicinity of synovial vessels. PTH also decreased type I collagen, MCP-1, and MMP-13 expression (P < 0.05), as well as PCNA staining compared to vehicle-treated OPOA rabbits. CONCLUSIONS: In our model of OA aggravated by previous OP, synoviopathy correlated well with cartilage damage. Intermittent PTH [1-34] administration ameliorated both hyperplasia and fibrosis.

Harmonisation of in-silico next-generation sequencing based methods for diagnostics and surveillance.

Improvements in cost and speed of next generation sequencing (NGS) have provided a new pathway for delivering disease diagnosis, molecular typing, and detection of antimicrobial resistance (AMR). Numerous published methods and protocols exist, but a lack of harmonisation has hampered meaningful comparisons between results produced by different methods/protocols vital for global genomic diagnostics and surveillance. As an exemplar, this study evaluated the sensitivity and specificity of five well-established in-silico AMR detection software where the genotype results produced from running a panel of 436 Escherichia coli were compared to their AMR phenotypes, with the latter used as gold-standard. The pipelines exploited previously known genotype-phenotype associations. No significant differences in software performance were observed. As a consequence, efforts to harmonise AMR predictions from sequence data should focus on: (1) establishing universal minimum to assess performance thresholds (e.g. a control isolate panel, minimum sensitivity/specificity thresholds); (2) standardising AMR gene identifiers in reference databases and gene nomenclature; (3) producing consistent genotype/phenotype correlations. The study also revealed limitations of in-silico technology on detecting resistance to certain antimicrobials due to lack of specific fine-tuning options in bioinformatics tool or a lack of representation of resistance mechanisms in reference databases. Lastly, we noted user friendliness of tools was also an important consideration. Therefore, our recommendations are timely for widespread standardisation of bioinformatics for genomic diagnostics and surveillance globally.

Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis.

PURPOSE: Impairment of subchondral bone density and quality aggravates cartilage damage in osteoarthritis (OA). Accordingly, we assessed whether improving microstructure and quality at subchondral bone by the bone-forming agent parathyroid hormone (PTH) [1-34] prevent cartilage damage progression in a rabbit model of OA preceded by osteoporosis (OP). METHODS: OP was induced in 20 female rabbits. At week 7, these rabbits underwent knee surgery to induce OA and, at week 12, they started either saline vehicle (n=10) or PTH (n=10) for 10 weeks. Ten healthy animals were used as controls. At week 22, microstructure was assessed by micro-computed tomography and bone remodelling by protein expression of alkaline phosphatase (ALP), metalloproteinase-9 (MMP9), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) at subchondral bone. Cartilage damage was evaluated using Mankin score. RESULTS: PTH reversed the decrease of bone area/tissue area, trabecular thickness, plate thickness, polar moment of inertia, ALP expression and OPG/RANKL ratio, as well as counteracted the increase of fractal dimension and MMP9 expression at subchondral bone of osteoarthritis preceded by osteoporosis (OPOA) rabbits compared to vehicle administration (P<0.05). Likewise, PTH decreased cartilage damage severity in OPOA rabbits. Good correlations were observed between subchondral bone structure or remodelling parameters, and cartilage Mankin score. CONCLUSIONS: Improvement of microstructural and remodelling parameters at subchondral bone by PTH [1-34] contributed to prevent cartilage damage progression in rabbits with early OPOA. These findings support the role of subchondral bone in OA. Further studies are warranted to establish the place of bone-forming agents as potential treatment in OA.

Coping with uncertainty: breeding adjustments to an unpredictable environment in an opportunistic raptor.

No environment is truly constant in time. As a result, animals have evolved multiple adjustments to cope with such fluctuations. However, the allocation of effort to costly activities that imply long-term commitments, such as breeding, may be extremely challenging when future resources change constantly and unpredictably, a context that has received little investigation. To fill this gap, we studied the breeding response by a wetland-dependent raptor, the black kite Milvus migrans, to within and between-years fluctuations in resource availability (inundation levels). The breeding performance of the population was decomposed into reproductive components expressed in a sequence of successive tasks along the breeding cycle (e.g. timing of laying, clutch size, hatching success, brood reduction). Variation in each component was related to resource levels observed at different key dates of the season in order to test whether and when population-level reproduction was adjusted to available resources. Along a 22-year time-series, inundation levels fluctuated unpredictably within and among years, and mostly affected the later components of kites' reproduction, such as hatching success and the incidence of brood reduction, which were the main determinants of the population yearly breeding output. Results were consistent with multiple adjustments to cope with uncertainty. As the season progressed and resources became easier to assess, a bet-hedging waiting strategy based on a conservatively small, invariant and asynchronous clutch gave way to real-time resource-tracking mechanisms mediated by progressive adjustments to current prey availability, so that population-level breeding rates were determined and tuned to resources rather late in the season. Such adjustments were the likely outcome of the interaction between parental tactics and environmental constraints. Behavioural flexibility, such as dietary opportunism, probably promoted further resistance to resource oscillations. Given that all ecosystems show some degree of unpredictability, resource-tracking adjustments, such as the ones depicted here, are likely to be commonplace in most communities.

European Registry on Helicobacter pylori management: Single-capsule bismuth quadruple therapy is effective in real-world clinical practice.

BACKGROUND: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. OBJECTIVE: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. METHODS: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. RESULTS: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. CONCLUSIONS: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.

MED and PSACH COMP mutations affect chondrogenesis in chicken limb bud micromass cultures.

Mutations in cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We studied the effects of over-expression of wild type and mutant COMP on early stages of chondrogenesis in chicken limb bud micromass cultures. Cells were transduced with RCAS virus harboring wild type or mutant (C328R, PSACH; T585R, MED) COMP cDNAs and cultured for 3, 4, and 5 days. The effect of COMP constructs on chondrogenesis was assessed by analyzing mRNA and protein expression of several COMP binding partners. Cell viability was assayed, and evaluation of apoptosis was performed by monitoring caspase 3 processing. Over-expression of COMP, and especially expression of COMP mutants, had a profound affect on the expression of syndecan 3 and tenascin C, early markers of chondrogenesis. Over-expression of COMP did not affect levels of type II collagen or matrilin-3; however, there were increases in type IX collagen expression and sulfated proteoglycan synthesis, particularly at day 5 of harvest. In contrast to cells over-expressing COMP, cells with mutant COMP showed reduction in type IX collagen expression and increased matrilin 3 expression. Finally, reduction in cell viability, and increased activity of caspase 3, at days 4 and 5, were observed in cultures expressing either wild type or mutant COMP. MED, and PSACH mutations, despite displaying phenotypic differences, demonstrated only subtle differences in their cellular viability and mRNA and protein expression of components of the extracellular matrix, including those that interact with COMP. These results suggest that COMP mutations, by disrupting normal interactions between COMP and its binding partners, significantly affect chondrogenesis.

Chondroitin sulfate improves synovitis in rabbits with chronic antigen-induced arthritis.

OBJECTIVE: Our aim was to explore the effect of chondroitin sulfate (CS), a natural glycosaminoglycan with attributed anti-inflammatory properties, on synovitis in a rabbit model of chronic arthritis with intense systemic inflammation bolstered by endothelial lesion and atherosclerotic diet. METHODS: Chronic arthritis was induced by intraarticular injections of ovalbumin in immunized rabbits. Systemic inflammation was boosted in these rabbits by receiving a hyperlipidemic diet after producing an endothelial lesion in the femoral arteries. A group of these rabbits were treated with CS (100mg/kg/day). At sacrifice, synovial membranes were isolated, and cyclooxygenase-2 (COX-2) and chemokine (C-C motif) ligand 2 (CCL2) mRNA, as well as protein expression were assayed by quantitative real-time polymerase chain reaction (RT-PCR) and western blot studies. Histological synovial examination was also carried out employing the histopathological synovitis score (Krenn scale). RESULTS: CS diminished both gene expression and protein synthesis of COX-2 and CCL2, and the histopathological score of the synovial membrane, when compared to untreated rabbits. In fact, CS partially prevented the intimal layer proliferation and the inflammatory cell infiltration in the synovial membrane, which was observed in non-treated animals. CONCLUSION: CS reduced the inflammatory response of the synovial membrane, as well as decreased the synovial histopathological lesions in our animal model. Further studies are warranted to demonstrate whether CS might be beneficial in the treatment of inflammatory arthritis.