Comparative study on the preventing effects of oral vanadyl sulfate and dietary restriction on the age-related glucose intolerance in rats.

BACKGROUND AND AIMS: Aging is associated with a progressive impairment of glucose tolerance. The aim of this study was to explore the protective effects of the chronic oral administration of the insulino-mimetic agent vanadyl sulfate (VOSO4) as compared with those exerted by a long-lasting dietary restriction. METHODS: Male Sprague-Dawley rats, either fed ad libitum (AL) or subjected to 40% dietary restriction (DR), were used. VOSO4 (0.5 mg/mL drinking water) was administered to a subgroup of AL rats for two months, starting at 16 months of age. Rats were subjected to an intravenous glucose tolerance test (IVGTT) at 16 and 18 months of age. Finally, the beta-cell responsiveness to glucose was evaluated in vitro by the isolated perfused pancreas preparation. RESULTS: The IVGTT performed in 16-month-old rats showed that DR prevented the development of the moderate glucose intolerance observed in AL rats. The IVGTT performed at 18 months of age confirmed the beneficial effect of DR and showed that VOSO4 was able to prevent the further age-related progression of glucose intolerance observed in AL rats. Pancreas perfusion studies showed that no increase in insulin secretion occurred in both VOSO4-treated and DR rats with respect to the age-matched AL controls, consistently with the in vivo observation of post-loading insulinaemic changes. CONCLUSIONS: On the basis of these results, we conclude that the beneficial effect of both treatments is mostly related to an improvement of tissue sensitivity to insulin rather than to an insulinotropic effect

The Impact of Specific Viruses on Clinical Outcome in Children Presenting with Acute Heart Failure

Abstract: The presence and type of viral genomes have been suggested as the main etiology for inflammatory dilated cardiomyopathy. Information on the clinical implication of this finding in a large population of children is lacking. We evaluated the prevalence, type, and clinical impact of specific viral genomes in endomyocardial biopsies (EMB) collected between 2001 and 2013 among 63 children admitted to our hospital for acute heart failure (median age 2.8 years). Viral genome was searched by polymerase chain reaction (PCR). Patients underwent a complete two-dimensional echocardiographic examination at hospital admission and at discharge and were followed-up for 10 years. Twenty-seven adverse events (7 deaths and 20 cardiac transplantations) occurred during the follow-up. Viral genome was amplified in 19/63 biopsies (35%); PVB19 was the most commonly isolated virus. Presence of specific viral genome was associated with a significant recovery in ejection fraction, compared to patients without viral evidence (p < 0.05). In Cox-regression analysis, higher survival rate was related to virus-positive biopsies (p < 0.05). When comparing long-term prognosis among different viral groups, a trend towards better prognosis was observed in the presence of isolated Parvovirus B19 (PVB19) (p = 0.07). In our series, presence of a virus-positive EMB (mainly PVB19) was associated with improvement over time in cardiac function and better long-term prognosis

Possible added value of thyroglobulin antibody (TgAb) testing in the evaluation of thyroidal status of subjects with overweight or obesity

Purpose: An increase in serum TSH concentrations in the absence of thyroid disease, named isolated hyperthyrotropinemia, is frequently observed in subjects with obesity. It is directly associated with body mass index, and it is reversible following weight loss. Autoimmune hypothyroidism is frequently associated with obesity, it is usually progressive and needs replacement treatment with L-thyroxine. The aim of this study was to investigate the role of thyroglobulin antibodies (TgAb) to define the thyroidal status in subjects with overweight or obesity. Methods: This is a retrospective study including 749 consecutive adult patients with overweight or obesity. Of those, 76 were excluded from the analysis due to hyperthyroidism, previous thyroidectomy or radioiodine therapy for hyperthyroidism, hemiagenesis or drug-induced hypothyroidism. Serum thyrotropin (TSH), free thyroxine (FT4), free 3,5,3'-triiodothyronine (FT3), TgAb and thyroperoxidase antibodies (TPOAb) were measured in all patients. Results: Out of 673 patients, 408 did not have thyroid disease. Among patients with thyroid disease (n = 265), 130 had nodular disease with no humoral signs of thyroid autoimmunity and 135 (20%) had autoimmune thyroiditis, defined by the presence of TPOAb and/or TgAb. The prevalence of hyperthyrotropinemia, either directly measured or presumed based on L-thyroxine treatment at the time of data collection, was 63.9% in patients with both TgAb and TPOAb, 47.1% in those with isolated positivity of TPOAb, 42.8% in patients with isolated positivity of TgAb, and 14.5% in those with no detectable TgAb or TPOAb. Conclusions: Our results confirm a high prevalence of autoimmune thyroiditis (20%) in patients with obesity. TgAb may be associated with hypothyroidism in the absence of TPOAb. TgAb measurement may turn helpful to unravel a proportion of subjects that may have or may develop primary hypothyroidism requiring specific substitutive treatment

The expression of platelet serotonin transporter (SERT) in human obesity

Serotonin (5-HT) is a well-known modulator of eating behavior. However, the molecular mechanisms linking its action to body weight balance have been only partially elucidated. Since platelets are a suitable peripheral model to study 5-HT transport, metabolism and release, we herein evaluated the expression of the platelet 5-HT re-uptake system (SERT) by [3H]-paroxetine binding assay. A cohort of 114 unrelated individuals (34 males, 80 females; age, mean +/- SD: 38.57 +/- 12.47 years) without major psychiatric disorders, was recruited following a naturalistic design regarding age or gender and classified accordingly to their body mass index (BMI). Subjects were divided into 5 groups: normal-weight (NW), overweight (OW) and grade I-III obese (OB) individuals. For gender analyses, data were transformed into [3H]-paroxetine density (Bmax)/BMI ratios to overcome both the disparity of women vs. men number and anthropometric differences between sexes.[3H]-paroxetine Bmax (SERT density, fmol/mg proteins) was reduced in platelet membranes of grade II (p &lt; 0.01) and III (p &lt; 0.001) obese subjects vs. controls and in overweight subjects (p &lt; 0.05) vs. grade III obese individuals. Considering all patients together, a strong negative correlation between Bmax and BMI (r = -0.449; P &lt; 0.0001) was demonstrated. Conversely, [3H]-paroxetine KD (dissociation constant, nM) did not differ among groups. No gender-related variation concerning Bmax/BMI ratios was observed in this cohort of subjects.The down-regulation of SERT in platelet membranes of severe human obesity (BMI &gt; 35 Kg/m2) confirms the involvement of 5-HT system in body weight gain. Moreover, this findings may help to elucidate those monoamine-endocrine networks acting on fat storage, adipocyte signaling and energy balance. Targeting 5-HT/5-HT-related markers will possibly uncover the existence of human obesity subtypes

Self-tolerance in multiple sclerosis

During the last decade, several defects in self-tolerance have been identified in multiple sclerosis. Dysfunction in central tolerance leads to the thymic output of antigen-specific T cells with T cell receptor alterations favouring autoimmune reactions. In addition, premature thymic involution results in a reduced export of naïve regulatory T cells, the fully suppressive clone. Alterations in peripheral tolerance concern costimulatory molecules as well as transcriptional and epigenetic mechanisms. Recent data underline the key role of regulatory T cells that suppress Th1 and Th17 effector cell responses and whose immunosuppressive activity is impaired in patients with multiple sclerosis. Those recent observations suggest that a defect in self-tolerance homeostasis might be the primary mover of multiple sclerosis leading to subsequent immune attacks, inflammation and neurodegeneration. The concept of multiple sclerosis as a consequence of the failure of central and peripheral tolerance mechanisms to maintain a self-tolerance state, particularly of regulatory T cells, may have therapeutic implications. Restoring normal thymic output and suppressive functions of regulatory T cells appears an appealing approach. Regulatory T cells suppress the general local immune response via bystander effects rather than through individual antigen-specific responses. Interestingly, the beneficial effects of currently approved immunomodulators (interferons β and glatiramer acetate) are associated with a restored regulatory T cell homeostasis. However, the feedback regulation between Th1 and Th17 effector cells and regulatory T cells is not so simple and tolerogenic mechanisms also involve other regulatory cells such as B cells, dendritic cells and CD56bright natural killer cells

COVID-19: A review on diagnosis, treatment, and prophylaxis

Coronavirus 2 (CoV) Severe Acute Respiratory Syndrome (SARS-CoV2) is causing a highly infectious pandemic pneumonia. Coronaviruses are positive sense single-stranded RNA viruses that infect several animal species, causing symptoms that range from those similar to the common cold to severe respiratory syndrome. The Angiotensin Converting Enzyme 2 (ACE2) is the SARS-CoV2 functional receptor. Measures are currently undertaken worldwide to control the infection to avoid disruption of the social and economic equilibrium, especially in countries with poor healthcare resources. In a guarded optimistic view, we hope that the undertaken preventive and treatment measures will at least contribute to contain viral diffusion, attenuate activity, or even eliminate SARS-CoV2. In this review, we discuss emerging perspectives for prevention/treatment of COVID-19 infection. In addition to vaccines under development, passive immunization is an open opportunity since patients develop neutralizing antibodies. A full spectrum of potential drugs for COVID-19 infections could in turn affect virus binding or enzymatic activities involved in viral replication and transcription. Furthermore, clinical trials are currently evaluating the safety and efficacy of anti-inflammatory drugs, such as tocilizumab. Bioinformatics may allow characterization of specific CD8+ and CD4+ T cell responses; thus, CoV2 T cells' frequency can be correlated with the disease severity and outcome. Combinatorial antibody phage display may be empowered to identify the immune repertoire of CoV2-specific neutralizing antibodies