Association between vitamin A and E and apolipoprotein A and B levels in type 2 diabetes

Objective. To determine the relationship between serum vitamin A and E and apolipoprotein levels in type 2 diabetic patients. Setting. Shariati Hospital, Tehran, Iran. Subjects and methods. One hundred and seventeen eligible type 2 diabetic patients who attended the Endocrine Research and Metabolism Center between 2002 and 2004 were enrolled in the study. Blood samples were collected after a 12 - 14-hour overnight fast for the measurement of serum levels of total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein (apo) A1 and apoB, and vitamins A and E. Anthropometric indices were determined by physical examination. Data were analysed statistically using Pearson's coefficient, multiple regression, and partial and bivariate correlations. Results. The mean body mass index (BMI) of the subjects was 27.4 ± 3.7 kg/m2. The mean (± standard deviation (SD)) serum levels of vitamins A and E were 0.5 ± 0.1 &#956;g/ml and 9.5 ± 2.6 &#956;g/ml, respectively. There were no significant differences in the plasma levels of vitamins A and E in males and females. Mean serum levels of vitamins A and E were within the normal range for both sexes. Serum lipid levels (total cholesterol, triglyceride and apoB) correlated with serum levels of vitamin E (p < 0.05). Serum levels of vitamins A and E were also correlated (p < 0.05). Standardised vitamin E levels showed significant negative correlation with most studied lipid profiles (p < 0.05). Conclusion. This study found that mean serum levels of the natural antioxidants vitamin E, and especially vitamin A, were close to the lower end of the normal range of these antioxidants in type 2 diabetics. Also, serum vitamin E and standardised vitamin E levels were important predictors of serum apoA1 levels in these patients. South African Journal of Clinical Nutrition Vol. 19(1) 2006: 39-4

Precision Dosing of Intravenous Tocilizumab:Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis

Background:Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy.Methods:A population pharmacokinetic model of intravenous tocilizumab was developed using data from a randomized controlled trial of dose tapering in patients with RA. Subsequent population-level Monte Carlo and individual Bayesian simulations were performed to create tapering strategies involving dose reduction and interval extension. The target trough concentration of tocilizumab was 5 mg/L. Finally, the drug savings were compared between the 2 methods.Results:The pharmacokinetic of tocilizumab was described with a 2-compartment model with parallel linear (CL 0.20 L/d) and nonlinear (VM 5.2 mg/d, KM 0.19 mg/L) elimination. The linear clearance rate and central volume of distribution increased with lean body mass, and men exhibited higher clearance rates than women. The simulated concentration-time profiles demonstrated that, owing to nonlinear clearance, drug concentrations decreased more than dose-proportionally with lower doses. Tapering based on an individual Bayesian approach emerged as the most promising strategy, yielding a 39% reduction in drug use across virtual populations.Conclusions:Tapering strategies were developed for intravenous tocilizumab, offering potential application in patients with RA who have reached low disease activity or remission, pending clinical validation. The developed strategies demonstrate that the tapering of tocilizumab should be approached more carefully and in smaller steps than that of TNFi

Tegumentary leishmaniasis and coinfections other than HIV

<div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes

Efficacy of cryotherapy for the treatment of cutaneous leishmaniasis: meta-analyses of clinical trials

BACKGROUND: Cryotherapy is a local treatment for cutaneous leishmaniasis with variable efficacy and greater safety than conventional treatment. The objective of this study is to evaluate the efficacy and safety of cryotherapy for the treatment of cutaneous leishmaniasis and to compare it with pentavalent antimonials. METHODS: A meta-analysis based on a search of nine databases with eight strategies was conducted. Inclusion and exclusion criteria were applied, the methodological quality of each article was evaluated, and the reproducibility of the study selection and information extraction from each clinical trial was assured. The per lesion and per patient efficacy was calculated, and a meta-analysis of relative risks with the random effects model and the Dersimonian and Laird's, Begg, and Egger tests, along with a sensitivity analysis, were performed. A meta-regression based on the methodological quality of the trials included was also performed. RESULTS: Eight studies were included in which respective per lesion efficacies of 67.3 % and 67.7 % were reported for cryotherapy and pentavalent antimonials. In 271 patients treated with cryotherapy and in 199 with pentavalent antimonials, respective per protocol and intent to treat efficacies of 63.6 % and 54.2 % were found in the first group, and per protocol and intent to treat efficacies of 74.7 % and 68.3 % were found in the second group. The relative risk for the comparison of efficacy in the two groups was 0.73 (0.42–1.29). The results of the sensitivity analysis and the meta-regression analysis of relative risks were statistically equal to the overall results. CONCLUSION: This investigation provides evidence in favor of the use of cryotherapy given that its efficacy is similar to that of pentavalent antimonials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1663-3) contains supplementary material, which is available to authorized users

Treatment of American tegumentary leishmaniasis in special populations : a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making

COMPARISON OF THE THERAPEUTIC EFFECTS OF TOPICAL SOLUTION OF ZINC SULFATE AND ORAL POLIO VACCINE IN PREVENTING THE RECURRENT HERPES SIMPLEX INFECTIONS

More than 85 of the world population are infected with herpes simplex virus. Inability to eradicate it after infection is one of the unique characteristics of this virus. Numerous methods have been tried out in the treatment and prevention of recurrent episodes and its complications. However, research to find out an effective, inexpensive, accessible method with low complications is still to be conducted. This study is conducted to compare the effectiveness of topical solution of zinc sulfate with that of oral polio vaccine in preventing the recurrent herpes simplex infections. In this prospective clinical trial, 60 patients with recurrent herpes simplex (with more than 3 recurrences per year) were treated with 0.05 zinc sulfate solution and OPV (4 droplets each month for 3 consecutive months). Both groups were followed up for 6 months and the characteristics of each recurrence episode were examined in follow-up visits. Chisquare was utilized for analysis. According to the findings , statistical means of 3 follow - ups suggested significant effects of both zinc sulfate and OVP in reducing the frequency, severity and duration of episodes up to 60 to 70 at the end of sixth month (P=0.01); however, no significant difference was observed in the effectiveness of the two methods (P=0.192). Therefore it is concluded that zinc sulfate is an effective, available and low - cost treatment with delayed effects but equivalent to OVP in preventing recurrent herpes simplex episodes