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ID PMID Title PublicationDate abstract
22810302 IL-6 blockade attenuates the development of murine sclerodermatous chronic graft-versus-ho 2012 Dec Systemic sclerosis (scleroderma) is a connective tissue disease characterized by excessive extracellular matrix deposition in the skin and visceral organs. Serum IL-6 levels are reported to be elevated in human scleroderma and chronic graft-versus-host disease (cGVHD) patients. IL-6 blockade using anti-IL-6 receptor mAb (anti-IL-6R mAb) results in amelioration of the pathologic symptoms of some autoimmune diseases such as rheumatoid arthritis and juvenile idiopathic arthritis. In this study, we examined the effects of anti-IL-6R mAb on either prevention or treatment of murine sclerodermatous cGVHD (Scl-cGVHD). We found that serum IL-6 levels in Scl-cGVHD mice gradually increased after bone marrow transplantation. Administration of anti-IL-6R mAb attenuated the development of severe Scl-cGVHD and fibrosis and resulted in an increase in CD4(+)CD25(+)FoxP3(+) regulatory T cells. However, treatment of established Scl-cGVHD with anti-IL-6R mAb showed no effects on disease severity. The effects of anti-IL-6R mAb were mostly inhibited by anti-CD25 mAb. Together, our results indicate that IL-6 has an important role in the pathogenesis of Scl-cGVHD. IL-6 blockade may be an effective approach for preventing Scl-cGVHD and treating cGVHD and scleroderma in humans.
22676348 Hydroxychloroquine improves insulin sensitivity in obese non-diabetic individuals. 2012 Jun 7 INTRODUCTION: Hydroxychloroquine (HCQ) is a common disease modifying therapy for the treatment of rheumatoid arthritis (RA). Prior research suggests that HCQ may reduce the risk of diabetes mellitus in patients with RA. To investigate the mechanism of this effect, we examined the effect of HCQ on insulin resistance, insulin sensitivity, and pancreatic β-cell secretion of insulin in non-diabetic, obese subjects. METHODS: We recruited 13 obese, non-diabetic subjects without systemic inflammatory conditions for an open-label longitudinal study of HCQ 6.5 mg per kilogram per day for six weeks. Subjects underwent an oral glucose tolerance test at three time points: 0 weeks (pre-treatment with HCQ), 6 weeks (at the end of the HCQ treatment), and 12 weeks (6 weeks post HCQ-treatment). The Matsuda Insulin Sensitivity Index (ISI), HOMA-IR, and HOMA-B were compared across time-points. RESULTS: The mean age of the cohort was 49 years, 77% females and median body mass index was 36.1 kg/m2. After 6 weeks of HCQ therapy, ISI increased from a median (interquartile range) of 4.5 (2.3-7.8) to 8.9 (3.7-11.4) with a p-value of 0.040, and HOMA-IR decreased from a median of 2.1 (1.6-5.4) to 1.8 (1.02-2.1) with a p-value of 0.09. All these variables returned toward baseline at week 12. CONCLUSION: HCQ use for 6 weeks in non diabetic obese subjects was associated with a significant increase in ISI and trends toward reduced insulin resistance and insulin secretion. These data suggest that HCQ, a common medication used to treat RA, possesses beneficial effects upon insulin sensitization. Further study of the insulin sensitizing effects of HCQ in patients with RA is warranted.
21741009 Association between provider volume and comorbidity on hospital utilization and outcomes o 2011 Jun BACKGROUND/PURPOSE: The impact of provider volume, comorbidity and adverse outcomes on hospital utilization of total hip arthroplasty (THA) has not yet been studied scientifically in Taiwan. This study aimed to examine the relationship between surgeon/hospital volume, perioperative complications, acute infections and hospital utilization for patients who underwent primary (THA). METHODS: We analyzed National Health Insurance (NHI) annual reimbursement data for all hospital admissions due to primary THA between January 2005 and December 2006. A total of 9335 patients with rheumatoid arthritis, osteoarthritis, avascular necrosis and other joint disorders were identified. Multivari-ate regression analyses were used to assess the relationship between provider volume and hospital utilization and the risk of adverse outcomes. Statistical analyses were adjusted for patient age, gender, comorbidity, type of arthritis, as well as hospital attributes. RESULTS: Reversed linear associations were found among hospital utilization, surgeon volume, and comorbidity score. Patients with acute infection tended to stay 8 days more and cost NT$32,451 more than their counterparts. Patients with perioperative complication tended to stay 2.30 days more and cost NT$15,327 more than their counterparts. Longer hospital stay and higher total hospital charge were associated with patient's age and Charlson index. CONCLUSIONS: This study revealed that the volume of THAs performed by individual surgeons was a more important determinant of hospital utilization than hospital volume. Perioperative adverse events were associated with patients' age and comorbidity.
21831009 The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflamm 2011 Oct Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is associated with cardiovascular disease, inflammation, body weight regulation and cancer. Its serum levels facilitate the diagnosis and prognosis of cancer and vascular disease. Furthermore, its serum levels are a powerful predictor of all-cause mortality, suggesting a fundamental role in biological processes associated with ageing. In cancer, the data available suggest that MIC-1/GDF15 is antitumorigenic, but this may not always be the case as disease progresses. Cancer promoting effects of MIC-1/GDF15 may be due, in part, to effects on antitumour immunity. This is suggested by the anti-inflammatory and immunosuppressive properties of MIC-1/GDF15 in animal models of atherosclerosis and rheumatoid arthritis. Furthermore, in late-stage cancer, large amounts of MIC-1/GDF15 in the circulation suppress appetite and mediate cancer anorexia/cachexia, which can be reversed by monoclonal antibodies in animals. Available data suggest MIC-1/GDF15 may be an important molecule mediating the interplay between cancer, obesity and chronic inflammation.
21757889 Bee venom-associated Th1/Th2 immunoglobulin class switching results in immune tolerance of 2011 BACKGROUND/AIMS: Bee venom (BV) therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. This study was conducted to examine the therapeutic effect of BV on established lupus nephritis in New Zealand Black/White (NZB/W) F1 female mice. METHODS: Beginning at 18 weeks of age, mice were given a subcutaneous injection of either BV (3 mg/kg BW) or an equal volume of saline once a week until the end of the study. To examine the effect of BV on CD4+CD25+Foxp3+ regulatory T cells, splenocytes from NZB/W mice (23 weeks of age) were treated with BV (1 μg/ml) or PBS in the presence of anti-CD3ε (1 μg/ml) and anti-CD28 antibodies (4 μg/ml) for 48 h. RESULTS: BV administration delayed the development of proteinuria to a significant extent, prevented renal inflammation, reduced tubular damage, and reduced immune deposits in the glomeruli. Interestingly, CD4+CD25+ regulatory T cells were significantly increased in vitro and in vivo after BV treatment. CONCLUSION: Collectively, the administration of BV that has immune modulating effects represents an applicable treatment of lupus nephritis in NZB/W F1 mice.
21735057 Malignant lymphomas and autoimmunity-a single center experience from Hungary. 2012 Feb Autoimmune diseases and malignant lymphomas have numerous similarities in their etiology and pathogenesis. Patients with autoimmune disorders have increased risk to develop non-Hodgkin's lymphomas, yet little is known about the occurrence of autoimmune features within lymphoma patients. Our aim was to examine the prevalence of autoimmune diseases among patients with non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL). We reviewed 352 patients' charts with malignant lymphomas to assess the rate of associated autoimmune diseases. Of 231 NHL patients, 30 (12.9%) had autoimmune disorders, while there were 11 patients who suffered from more than one disease entity. It was Sjögren's syndrome that occurred in the largest number (eight cases), other frequent entities were undifferentiated connective tissue disease (seven), thyroiditis (six), rheumatoid arthritis (four), and systemic vasculitis (four). The female/male ratio was significantly different between patients with or without autoimmune diseases, while no other clinical features differed significantly between the two groups. Ten patients (33.3%) were initially diagnosed with lymphoma, 13 (43.3%) of them had already been diagnosed with autoimmune disease at the time of lymphoma occurrence. Six patients (20%) with previously diagnosed immunological disorder developed new autoimmune condition after the treatment of lymphoma. Lymphoma and autoimmune disease occurred simultaneously in one patient. Among the 121 HL patients, 14 (11.5%) had associated autoimmune disease. Ten patients developed thyroiditis after the lymphoma treatment, two had immune thrombocytopenia, and one had autoimmune hemolytic anemia. One female patient was diagnosed with systemic sclerosis 10 years before the onset of HL. Our results highlight that an increased risk for the development of autoimmune diseases should be considered in patients both with NHL and HL.
21734383 Infections and the liver. 2011 BACKGROUND: Hepatitis B (HBV) and hepatitis C virus (HCV) have infected nearly half a billion individuals worldwide and are major indications for liver transplantation. Key requirements to successful outcomes with modern antiviral drugs are favourable host factors. RESULTS: Single nucleotide polymorphisms near the IL28B gene location which encode for interferon (IFN)-λ3 have a large effect in determining the likelihood of patients obtaining a cure from pegylated IFN-α and ribavirin combination therapy or spontaneous clearance of the HCV. 80% of patients who carry two copies of this advantageous variant cleared the virus during IFN therapy and remained virus-free with a sustained viral response. This mutation is more common in Caucasian and Asian populations, whereas it is only found in the 40-50% of sub-Saharan Africans who are known to be more resistant to combination therapy. Similarly, host factors control tolerance to chronic HBV infection and can fluctuate over time with increased risk of progression to cirrhosis and particularly liver cancer. Loss of viral tolerance with reactivation and hepatitis is increasingly seen with the widespread use of biological treatments for diseases such as inflammatory bowel disease or rheumatoid arthritis. Natural disasters and conflicts in some parts of the world have also seen an increase in cases of hepatitis A and E virus infection and highlighted the global public health burden from viral-induced hepatitis. CONCLUSIONS: Increased appreciation of the interaction between host factors and the viral life cycles is likely to significantly alter the way we target these infections in the future.
21636628 Lack of association of interleukin-18 gene promoter -607 A/C polymorphism with susceptibil 2011 Aug OBJECTIVE: Published data on the association between interleukin (IL)-18 gene promoter -607 A/C polymorphism and autoimmune diseases risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A total of 17 studies, including six studies on type 1 diabetes (T1D), four on rheumatoid arthritis (RA), five on systemic lupus erythematosus (SLE), three on Crohn's Disease (CD) and three on ulcerative colitis (UC), were available for the meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), genotypes A/A + A/C (dominant effect), and A allele in fixed or random-effects models. RESULTS: Overall, no significantly elevated autoimmune diseases risk was found in all genetic models when all studies were pooled into the meta-analysis. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for A-allele were T1D (OR = 0.938, 95% CI = 0.757-1.162), RA (OR = 0.759, 95% CI = 0.540-1.067), SLE (OR = 0.858, 95% CI = 0.609-1.208), CD (OR = 1.159, 95% CI = 0.975-1.379) and UC (OR = 1.170, 95% CI = 0.977-1.402), respectively. In the subgroup analysis by ethnicity, there was still no significant association detected in all genetic models. CONCLUSIONS: To date, there is still not enough evidence to indicate the association of IL-18 gene promoter -607 A/C polymorphism and the development of autoimmune diseases.
21621603 Safety of infliximab use during pregnancy. 2011 Jul Infliximab is a chimeric IgG1 monoclonal antibody to tumor necrosis factor alpha (TNF)-α used in the treatment of inflammatory bowel disease and rheumatoid arthritis. Infliximab does not actively cross the placenta during the first trimester, but undergoes efficient placental transfer during the late second and third trimesters and is detectable in the infant's serum for several months after birth. This raises concerns about immunological risks of infection and response to vaccines. Available evidence from registry studies and case reports involving more than 300 pregnancy outcomes suggest that infliximab carries low fetal risk and is compatible with use during conception and the first two trimesters of pregnancy. The long-term effects of infliximab exposure on the developing immune system are yet unknown. Based on limited data from several case reports, infants born with detectable levels of infliximab do not seem to have an increased risk of infections in their first year of life and have normal responses to nonlive vaccines. However, a fatal case of disseminated mycobacterial infection has been reported in an infant who received BCG vaccine at 3 months of age, to a mother who had been treated with infliximab throughout her pregnancy. Vaccination with live viruses should be postponed in infants exposed to infliximab in utero, until serum levels are undetectable which may require more than 6 months. Discontinuing infliximab early in the third trimester should be considered in order to minimize late fetal exposure.
21523317 Integrating evidence in disability evaluation by social insurance physicians. 2011 Nov OBJECTIVE: The aim of this study was to explore applying the method of evidence-based medicine (EBM) to resolve common questions in the field of disability evaluation. METHODS: We used three clinical questions corresponding to problems encountered by insurance physicians in daily practice to explore opportunities for and barriers to the application of EBM. The questions fell under two topics: the prognosis of work ability and the effectiveness of interventions to enhance work participation. We used the four-step EBM strategy: (i) formulation of a clinical question, (ii) searching the literature, (iii) appraisal of the evidence, and (iv) implementation of the findings into clinical practice. We restricted the searches to PubMed (Medline). RESULTS: For rheumatoid arthritis, we found evidence on the prognosis of work disability over a long-term period. For remaining sciatica after lumbar discectomy, we found evidence for the stability of the limitations at this stage. For depression with co-morbid alcoholism, we found evidence that treatment of both conditions would enhance work participation. The searches were effective and efficient. The interpretation of the findings was hampered by a lack of consensus in the literature about outcomes such as the concept of a poor prognosis of work ability. CONCLUSIONS: The EBM strategy and methods can be used by social insurance physicians to find and apply evidence for common questions in disability evaluation. The World Health Organization's International Classification of Functioning, Disability, and Health (ICF) model is instrumental in this, although more consensus on central outcome measures is needed. Further research is needed on the translation of evidence into practice. Development of valid specific search strategies for physicians in disability evaluation would improve the implementation of EBM.
21474028 Continuous bilateral posterior lumbar plexus block with a disposable infusion pump: case r 2011 Mar BACKGROUND AND OBJECTIVES: The number of bilateral total hip arthroplasties (THA) has been increasing every year. Postoperative analgesia by continuous perineural infusion of local anesthetic has been shown favorable results when compared to systemic analgesia. The use of elastomeric pumps has increased patient satisfaction when compared to electronic models. The objective of this report was to describe a case of continuous bilateral posterior lumbar plexus block with an elastomeric infusion pump in a patient submitted to bilateral hip arthroplasty. CASE REPORT: This is a 46 year-old female patient weighing 65 kg, 162 cm, with rheumatoid arthritis and hypertension, physical status ASA II, scheduled for bilateral THA in a single stage. She had been on corticosteroids for 13 years. Hemoglobin=10.1 g.dL⁻¹, hematocrit=32.7%. Routine monitoring. Spinal anesthesia with 15 mg of 0.5% isobaric bupivacaine. General anesthesia with propofol (PFS) and remifentanil, and intubation without neuromuscular blockers. Right THA and, at the end, lumbar plexus block with a stimulator and a set of 150 mm needle and injection of 20 mL of 0.2% bupivacaine and introduction of a catheter. Left THA and, at the end, the same procedure. Anesthetic dispersion and contrast were investigated. Elastomeric pump was installed with 0.1% bupivacaine (400 mL) at a rate of 14 mL.h⁻¹. The patient was transferred to the Intensive Care Unit (ICU). After 24 hour, a new pump was installed with the same solution. She did not receive any boluses for 50 hours. After removal of the catheter, pain was controlled with oral ketoprofen and dypirone. CONCLUSIONS: Continuous peripheral blockade with infusion of 0.1% bupivacaine with elastomeric pumps is a safe and effective procedure in adults.
21415774 Vitamin D: a d-lightful solution for health. 2011 Aug Throughout evolution, sunlight-produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet, it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis, making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis, increasing risk of fracture. Essentially, every tissue and cell in the body has a vitamin D receptor. Therefore, vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, types I and II diabetes, heart disease, dementia, deadly cancers, and infectious diseases. Therefore, sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.
21393631 Recent advances in IL-22 biology. 2011 Mar Several cell types, in particular epithelial cells, express the receptor for the cytokine IL-22 and upon its recognition produce molecules that are active both locally and systemically. Many different types of lymphocyte secrete IL-22. T(h)17 cells produce IL-22 although the optimal conditions for secretion of IL-17 or IL-22 by T(h)17 cells differ, as do the transcription factors involved. Aryl hydrocarbon receptor is required for IL-22 production by T(h)17, T(h)22 and γδ T cells. T(h)22 cells produce IL-22 in response to IL-6 and tumor necrosis factor α (TNF-α), particularly in the skin, whereas γδ T cells produce IL-22 in response to IL-23, particularly in the lung. NK cells produce IL-22 in response to IL-12 and IL-18 or IL-23. Retinoic acid-related orphan receptorγt-positive innate lymphoid cells, including lymphoid tissue inducer (LTi) and LTi-like cells express IL-22 with IL-23 again enhancing expression. IL-22 is known to be expressed in many chronic inflammatory conditions, including psoriasis and rheumatoid arthritis, and its up-regulation often correlates with disease activity. IL-22 is known to be protective in the gastrointestinal tract in inflammatory bowel disease but may mediate either harmful or helpful inflammatory responses in different models of intestinal infection. Finally, IL-22 may also play an important role in tissue repair.
21332888 The relative burden of haemophilia A and the impact of target joint development on health- 2011 May Studies with haemophilia A (HA) patients have shown burden in health-related quality of life (HRQOL) when compared with general population norms. In the current study, HA patients' SF-36v2 health survey scores were compared with general population norms and to patients with other chronic conditions. The impact of target joints (TJs) on HRQOL was also examined. The sample was a subset of HA patients enrolled in the Post-Authorization Safety Surveillance (PASS) programme: a prospective open-label study in which ADVATE [Antihaemophilic Factor (Recombinant), Plasma/Albumin-Free Method] was prescribed. A total of 205 patients who were ≥ 18 years old and had SF-36v2 baseline scores were selected for this study. To measure the burden of HA on HRQOL, manova analyses compared these SF-36v2 scores to age- and gender-matched general population US and EU norms and to patients from other chronic condition groups. manova and correlational analyses examined the relations among TJ, age and SF-36v2 scores. Comparisons with general population norms confirm that HA negatively impacts physical, but not mental, HRQOL. Comparison with other chronic conditions shows the physical burden of HA is greater than for chronic back pain but similar to diabetes and rheumatoid arthritis, while the mental burden of HA is less than for all three patient groups. The presence of TJs was negatively associated with physical HRQOL, although this association was much larger for older patients (45+ years) than for younger ones. Physical, but not mental, HRQOL is diminished in HA patients. Target joints are associated with lower physical HRQOL, although this effect is moderated by age.
20963466 Association of increased serum IL-33 levels with clinical and laboratory characteristics o 2011 Jun Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. Although interleukin-33 (IL-33), a novel number of the IL-1 family, has been reported to have proinflammatory effects, the association of IL-33 with SLE has remained unknown. The aim of this study was to examine whether the serum IL-33 level is associated with SLE. A total of 70 patients with SLE were recruited. Sera from these patients were obtained at their visit and were compared to sera from 40 healthy controls or 28 patients with rheumatoid arthritis (RA) for IL-33 level. Furthermore, blood samples from patients with SLE were determined for various SLE-related laboratory variables, including blood routine, complements, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and some autoantibodies. Serum IL-33 level was significantly increased in patients with SLE, compared with healthy controls, but was lower than that with RA. In patients with SLE, most clinical and laboratory characteristics did not correlate with serum IL-33 levels, with exceptions of thrombocytopenia, erythrocytopenia, anti-SSB antibody, ESR, CRP and IgA. By Spearman's correlation coefficient, patients with SLE showed close correlation of IL-33 with ESR, CRP and IgA, and by multivariate logistic regressions, patients with SLE showed significantly independent association of IL-33 with thrombocytopenia, erythrocytopenia and anti-SSB antibody. Our results suggest that IL-33 may play a role in acute phase of SLE, but it was not associated with course of the disease. Moreover, IL-33 may exert biologic effects on erythrocytes and platelets or their precursors in SLE.
20583858 Substituted benzenediol Schiff bases as promising new anti-glycation agents. 2011 Feb A feature of diabetes is that the rate of protein glycation and the formation of advanced glycation endproducts (AGEs) increases spontaneously due to the abnormally elevated levels of sugar in the blood. The glycation of proteins is associated with a large number of late diabetic complications (retinopathy, neuropathy, atherosclerosis, end stage renal diseases, rheumatoid arthritis and neurodegenerative diseases). The increase in diabetic complications is a major cause of morbidity and mortality, which has increased significantly in the last two decades. Therefore, there is a considerable recent interest in the identification of lead molecules, which can inhibit the glycation process or slow it down considerably. A new class of anti-glycation agents has been identified, based on the spectrofluorimetric analysis of fluorescent advanced glycation endproducts (AGEs), benzenediol Schiff bases, and their structure-activity relationships have been studied. Some of these compounds have shown a promising anti-glycation potential in vitro.
23874059 The Importance of General Self-Efficacy for the Quality of Life of Adolescents with Chroni 2013 Aug We investigated the influence of general self-efficacy perceived by adolescents with chronic conditions and parents on quality of life. This cross-sectional study used the general self-efficacy scale and DISABKIDS condition-generic module to survey adolescents (92/293; 31 %) with type I diabetes, juvenile rheumatoid arthritis, cystic fibrosis, kidney/urological conditions, and neuromuscular disorders; and parents (121/293; 41 %). Self perceived and parents' perceived general self-efficacy of adolescents was compared using paired t-tests, and adolescents' quality of life and general self-efficacy were compared among conditions using analysis of variance. Bivariate correlations between general self-efficacy and quality of life were identified, and multiple regression sought predictors of quality of life after controlling for background variables. Social quality of life was lowest among those with neuromuscular disorders. General self-efficacy was highest among adolescents with cystic fibrosis and lowest among those with urological conditions. Parents' perceptions of general self-efficacy were higher than adolescents' (p ≤ 0.05), although absolute differences were small. General self-efficacy perceived by parents and adolescents was related to emotional, physical, and social quality of life. Adolescents' perceived self-efficacy predicted all quality of life domains. Parents' perceptions of the adolescents self-efficacy predicted the adolescents' social quality of life (β = 0.19; p ≤ 0.01). General self-efficacy of adolescents with chronic conditions as perceived by themselves and their parents is important for adolescents' quality of life. Interventions to improve general self-efficacy should benefit quality of life among these adolescents.
23420624 D-amino acid based protein arginine deiminase inhibitors: Synthesis, pharmacokinetics, and 2012 Oct 26 The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Since D-amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of D-amino acid analogs of our pan-PAD inhibitor Cl-amidine, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that d-Cl-amidine and d-o-F-amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of d-Cl-amidine were moderately improved over those of l-Cl-amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.
23200399 A novel HPLC-electrochemical detection approach for the determination of D-penicillamine i 2013 Jan 15 D-penicillamine is a thiol drug mainly used for Wilson's disease, rheumatoid arthritis and cystinuria. Adverse effects during normal use of the drug are frequent and may include skin lesions. To evaluate its toxic effects in clinical cases an original method based on high performance liquid chromatography coupled to amperometric detection in a specific biological matrix such as skin has been developed. The chromatographic analysis of D-penicillamine was carried out on a C18 column using a mixture of acid phosphate buffer and methanol as the mobile phase. Satisfactory sensitivity was obtained by oxidizing the molecule at +0.95 V with respect to an Ag/AgCl reference electrode. A chemical reduction of D-penicillamine-protein disulphide bonds using dithioerythritol combined with microwaves was necessary for the determination of the total amount of D-penicillamine in skin specimens. A further solid-phase extraction procedure on C18 cartridges was implemented for the sample clean-up. The whole analytical procedure was validated: high extraction yield (>91.0%) and satisfactory precision (RSD<6.8%) values were obtained. It was successfully applied to skin samples from a patient who was previously under a long-term, high-dose treatment with the drug and presented serious D-penicillamine-related dermatoses. Thus, the method seems to be suitable for the analysis of D-penicillamine in skin tissues.
26662743 Successful antibiotic treatment for subdural empyema and seizure due to methicillin-resist 2012 Nov Halo orthosis is used for cervical spine fixation after spinal surgery or injury. Although superficial infection at pin sites occurs frequently, intracranial development of infection, including brain abscesses, is very rare. We experienced subdural empyema due to methicillin-resistant Staphylococcus aureus (MRSA) caused by intracranial penetration of halo pins. A 38-year-old woman with a 4-year history of rheumatoid arthritis experienced severe myelopathy due to atlanto-axial dislocation and vertical subluxation. Reduction and immobilization using a halo vest resulted in neurologic improvement; she later underwent occipital bone to C2 fusion using posterior instrumentation. Three months after halo orthosis fixation, she complained of a headache, experienced a generalized tonic-clonic seizure, and became unconscious for 10 min. Computed tomography revealed pneumoencephalus, and Gd-enhanced magnetic resonance imaging revealed edema, enhancement of the overlying dura in the left partial lobe, and subdural and subarachnoidal empyema. Following removal of the halo vest, there was a purulent discharge from the left-posterior pin site. Culture of the discharge was positive for MRSA. The patient was treated with intravenous vancomycin for 2 weeks, followed by cefozopran hydrochloride for 4 weeks. Her symptoms improved, and additional surgery was not required. At latest follow-up, 10 years after the seizure, she is neurologically stable without any recurrence of the infection.