The spectrum of idiopathic inflammatory myopathies in South Africa

Clinical Rheumatology - There are many reports on idiopathic inflammatory myopathies (IIM) but little information from sub-Saharan Africa. We conducted a retrospective study of IIM in a...     

The TNF-derived TIP peptide activates the epithelial sodium channel and ameliorates experimental nephrotoxic serum nephritis

1. Download : Download high-res image (407KB)
2. Download : Download full-size image

     

Associated comorbidities in psoriasis and inflammatory bowel disease

Background The association between psoriasis and inflammatory bowel disease (IBD) has been previously reported although a great deal remains unknown about associated comorbidities. Objectives The aim of this study was to examine comorbidities in individuals diagnosed with both psoriasis and IBD, and to compare those with individuals diagnosed with psoriasis‐only. We also looked at differences within the IBD group by clearly defining that cohort. Methods We included 146 patients diagnosed with both psoriasis and IBD and 146 controls diagnosed of psoriasis‐only without previous records of IBD, matched by gender, ethnicity and age (±5 years). Patients were obtained from the research patient data repository of Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital. Controls were obtained from the psoriatic arthritis and psoriasis follow‐up study (PAFS) at BWH. The comparison between the two groups included socio‐demographics, comorbidities and laboratory inflammation parameters. Results Compared to individuals with psoriasis‐only, patients with both psoriasis and IBD had significantly higher rates of autoimmune thyroiditis (2.1% vs. 6.8%), hepatitis (0.7 vs. 6.2%) and diabetes (11.0% vs. 26.7%). In addition, of the 146 patients with psoriasis and IBD, 60 (41.1%) were diagnosed with seronegative arthritis. The average C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) of the last visits in our clinics were significantly elevated compared to the individuals with psoriasis‐only (ESR, 33.5 vs. 4.0 mm/h; CRP, 9.1 vs. 2.3 mg/L; both P‐values <0.0001). Conclusions We found that patients with both, psoriasis and IBD have a number of further associated comorbidities, some at significantly higher levels than individuals with psoriasis‐only. Common inflammatory pathways and genetic predispositions for specific patterns in the immune response may play an important role in the evolution of associated conditions.     

Automated radiosynthesis of [11C]UCB-J for imaging synaptic density by positron emission tomography

An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [¹¹C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/μmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [¹¹C]CH₃I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis.     

Theiler’s murine encephalomyelitis virus as an experimental model system to study the mechanism of blood–brain barrier disruption

Theiler’s murine encephalomyelitis virus is a widely used model to study the initiation and progression of multiple sclerosis. Many researchers have used this model to investigate how the immune system and genetic factors contribute to the disease process. Current research has highlighted the importance of cytotoxic CD8 T cells and specific major histocompatibility complex (MHC) class I alleles. Our lab has adopted this concept to create a novel mouse model to study the mechanism of blood–brain barrier (BBB) disruption, an integral feature of numerous neurological disorders. We have demonstrated that epitope-specific CD8 T cells cause disruption of the tight junction architecture and ensuing CNS vascular permeability in the absence of neutrophil support. This CD8 T cell-initiated BBB disruption is dependent on perforin expression. We have also elucidated a potential role for hematopoietic factors in this process. Despite having identical MHC class I molecules, similar inflammation in the CNS, and equivalent ability to utilize perforin, C57BL/6 mice are highly susceptible to this condition, while 129 SvIm mice are resistant. This susceptibility is transferable with the bone marrow compartment. These findings led us to conduct a comprehensive genetic analysis which has revealed a list of candidate genes implicated in regulating traits associated with BBB disruption. Future studies will continue to define the underlying molecular mechanism of CD8 T cell-initiated BBB disruption and may assist in the development of potential therapeutic approaches to ameliorate pathology associated with BBB disruption in neurological disorders.     

Experimental hypoglycemia is a human model of stress-induced hyperalgesia

Hypoglycemia is a physiological stress that leads to the release of stress hormones, such as catecholamines and glucocorticoids, and proinflammatory cytokines. These factors, in euglycemic animal models, are associated with stress-induced hyperalgesia. The primary aim of this study was to determine whether experimental hypoglycemia in humans would lead to a hyperalgesic state. In 2 separate 3-day admissions separated by 1 to 3 months, healthy study participants were exposed to two 2-hour euglycemic hyperinsulinemic clamps or two 2-hour hypoglycemic hyperinsulinemic clamps. Thermal quantitative sensory testing and thermal pain assessments were measured the day before and the day after euglycemia or hypoglycemia. In contrast to prior euglycemia exposure, prior hypoglycemia exposure resulted in enhanced pain sensitivity to hot and cold stimuli as well as enhanced temporal summation to repeated heat-pain stimuli. These findings suggest that prior exposure to hypoglycemia causes a state of enhanced pain sensitivity that is consistent with stress-induced hyperalgesia. This human model may provide a framework for hypothesis testing and targeted, mechanism-based pharmacological interventions to delineate the molecular basis of hyperalgesia and pain susceptibility.