Wernicke's encephalopathy following hyperemesis gravidarum

Wernicke''s encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B₁(thiamine) deficiency. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding. Most patients present with the triad of ocular signs, ataxia, and confusion. It can be associated with life-threatening complication like central pontine myelinolysis (CPM). We report two cases of WE following HG, with two different outcomes.     

A novel deletion mutation in the <Emphasis Type=Italic>TUSC3</Emphasis> gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability

Background  

Intellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 1-3% in a general population. In the past decades, the research focus has been predominantly on X-linked ID (68 loci and 19 genes for non syndromic X linked ID) while for autosomal recessive nonsyndromic ID (NSID) only 30 loci and 6 genes have been reported to date.     

Depletion of BAFF cytokine exacerbates infection in Pseudomonas aeruginosa infected mice

BackgroundCystic fibrosis (CF) is a genetic disease characterized by chronic inflammation of the lungs that is ineffective at clearing pathogens. B-cell activating factor (BAFF), a cytokine involved in the development of B-cells, is known to be elevated in CF patients with subclinical infections. We postulate that the elevated BAFF levels in CF patients might be triggered by Pseudomonas aeruginosa infection and it might play a protective role in the regulation of lung responses to infection.MethodsTo address this hypothesis, we used a well characterized model of CFTR.KO mice infected with a clinical strain of P. aeruginosa (PA508). We quantified cell types with flow cytometry, concentration of cytokines by ELISA tests, bacterial load by colony counting and lung physiology by metacholine-induced lung resistance.ResultsOur data demonstrates that BAFF is not elevated in uninfected CF mice, and infection with Pseudomonas leads to significant induction of this regulatory cytokine. We also demonstrate that the maintenance of BAFF levels and its induction during the infection is important for clearance of Pseudomonas infection as its depletion during the course of infection leads to decrease in the resolution of infection both in WT and CFTR-KO mice. Interestingly, the depletion of BAFF not only results in a depletion of B cells numbers but also to a significant decrease in the number of regulatory T cells in the non-infected lungs.ConclusionsOverall, our data demonstrate for the first time that BAFF is an important regulatory molecule helping to maintain the immunological response to infection and clearance of lung infection.     

Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma

Estrogen is implicated in many autoimmune diseases and is a robust immunomodulator. For example, it regulates interferon (IFN)-gamma, a cytokine believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in the literature is a lack of information on the regulation of nitric oxide in immune tissues by estrogen. We now show that activation of splenocytes with T cell stimulants [concanavalin-A (Con-A) or anti-CD3 antibodies] results in copious release of nitric oxide in splenocyte cultures from estrogen-treated but not placebo-treated mice. Moreover, even a low dose of T cell stimulants induced nitric oxide in splenocytes from estrogen-treated, but not placebo-treated, mice. Con-A-activated splenocytes from estrogen-treated mice also have up-regulated iNOS mRNA, iNOS protein, and cyclooxygenase-2 (a nitric oxide-regulated downstream proinflammatory protein) when compared with controls. Our studies suggest that the induction of nitric oxide by activated splenocytes from estrogen-treated mice is mediated in part by IFNgamma. First, blocking costimulatory signals mediated through interactions of CD28 and B7 molecules by CTLA-4Ig markedly decreased not only IFNgamma but also nitric oxide. Second, estrogen treatment of IFNgamma-knockout (IFNgamma(-)/(-)) mice did not induce iNOS protein or nitric oxide. Finally, in vitro addition of recombinant IFNgamma to Con-A-activated splenocytes from IFNgamma((-)/(-)) mice induced iNOS protein primarily in estrogen-treated mice. Overall, this is the first report to show that estrogen treatment up-regulates IFNgamma-inducible-iNOS gene expression, iNOS protein, nitric oxide, and cyclooxygenase-2 as an indirect consequence of activation of T cells. These findings may have wide implications to immunity and inflammatory disorders including female-predominant autoimmune diseases.     

Pediatric Patients with Chronic Kidney Disease-Mineral Bone Disorder

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism that has deleterious consequences on skeletal and cardiovascular health. Nowhere is the morbidity of this disorder more telling than in children. During childhood and adolescence, CKD-MBD may result in poor growth and skeletal deformities, while the mineral dysregulation can manifest in cardiovascular disease in early adulthood, a development that places the patients at high risk for severe morbidity and early mortality. Unfortunately, management of CKD-MBD has been less than satisfactory in children despite recent advances and is limited by the lack of evidence-based treatment guidelines. More positive are ongoing research efforts, such as the Chronic Kidney Disease in Children and the Cardiovascular Comorbidity in Children with CKD (4C) studies that are currently providing important insights which should help better elucidate the pathogenesis and progression of mineral dysregulation and its clinical impact in children. Data from these studies and others will undoubtedly also help formulate clinical trials and the generation of evidence-based therapeutic options designed to provide more effective management of CKD-MBD in the pediatric population.