Pancreatic lesions and metabolic aggravation are prevented by low doses of sitagliptin in a rat model of type 2 diabetes

Introduction: The management of type 2 diabetes is designed to reduce disease-related complications and improve long-term outcomes. Inhibition of dipeptidyl peptidase-4 (DPP-4) activity by sitagliptin has been shown to improve glycaemic control in patients with type 2 diabetes Mellitus (T2DM) by prolonging the actions of incretin hormones, but the real impact of low-dose sitagliptin treatment on cardiometabolic risk factors and pancreatic lesions is almost unknown. This study aimed to evaluate the effects of low doses of sitagliptin on cardiovascular risk factors and histological pancreas parameters in Zucker Diabetic Fatty rats (ZDF (fa/fa)) an animal model of T2DM. Materials and Methods: Twenty weeks old diabetic obese (fa/fa) ZDF male rats were treated with vehicle or sitagliptin (10 mg/kg BW/day) during 6 weeks (n=8 each). The following parameters were assessed: glycaemia, HbA1c, insulin, lipidic profile; blood pressure. Specimens for pancreatic histopathology were stained with haematoxylin-eosin and periodic-acid-Shiff, examined by light microscopy. Endocrine and exocrine pancreas was evaluated semiquantitatively concerning inflammatory infiltrate, fibrosis, vacuolization and congestion, and scored from 0 (absent) to 3 (severe and extensive damage). Results: Sitagliptin in diabetic obese ZDF rats promoted a positive effect on dysglycaemia, dyslipidaemia and prevented the increase of blood pressure. Endocrine and exocrine pancreas presented a reduction/amelioration of fibrosis severity, inflammatory infiltrate, intra-islet vacuolation, and congestion vs the vehicle-treated diabetic rats. Conclusion: Simultaneous improvement of a sustainable glycaemic profile and of pancreatic histopathological lesions supports the favorable cardiovascular risk profile and may prove beneficial in decreasing long-term complications of T2DM.The authors are very grateful to the support of Fundação Merck Sharp & Dohm

Emergent Biomarkers of Residual Cardiovascular Risk in Patients with Low HDL-c and/or High Triglycerides and Average LDL-c Concentrations: Focus on HDL Subpopulations, Oxidized LDL, Adiponectin, and Uric Acid

This study intended to determine the impact of HDL-c and/or TGs levels on patients with average LDL-c concentration, focusing on lipidic, oxidative, inflammatory, and angiogenic profiles. Patients with cardiovascular risk factors (n = 169) were divided into 4 subgroups, combining normal and low HDL-c with normal and high TGs patients. The following data was analyzed: BP, BMI, waist circumference and serum glucose, Total-c, TGs, LDL-c, oxidized-LDL, total HDL-c and HDL subpopulations, paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. The two populations with increased TGs levels, regardless of the normal or low HDL-c, presented obesity and higher waist circumference, Total-c, LDL-c, Ox-LDL, and uric acid. Adiponectin concentration was significantly lower and VEGF was higher in the population with cumulative low values of HDL-c and high values of TGs, while HDL quality was reduced in the populations with impaired values of HDL-c and/or TGs, viewed by reduced large and increased small HDL subfractions. In conclusion, in a population with cardiovascular risk factors, low HDL-c and/or high TGs concentrations seem to be associated with a poor cardiometabolic profile, despite average LDL-c levels. This condition, often called residual risk, is better evidenced by using both traditional and nontraditional CV biomarkers, including large and small HDL subfractions, Ox-LDL, adiponectin, VEGF, and uric acid.info:eu-repo/semantics/publishedVersio

Silicates as alternative pretreatment for cellulose pulp to obtain nanofibrils for application in biodegradable packaging: a technical review.

ABSTRACT Background: The production of cellulose microfibrils/nanofibrils (CMF/CNF) has attracted increasing attention in recent decades due to their excellent barrier, mechanical, and surface chemistry properties. However, large-scale industrial production of CMF/CNF has been a major challenge due to their high energy consumption, limiting their application. In this context, in recent years many studies have focused on developing pre-treatments designed to facilitate the fibrillation of CMF/CNF by reducing energy consumption during their production. This review highlights the latest advances in the use of silicates as chemical pre-treatments for CMF/CNF production, covering the main aspects related to the effects of chemical modification on the production and the properties of materials for application in biodegradable packaging. Results: Energy consumption reductions of up to 30% were achieved by pretreating cellulose pulps using silicates. In addition, the pre-treatments resulted in smaller CMF/CNF diameters and greater individualization of the nanofibrils. Studies evaluating the thermal stability, hydrophobicity, mechanical properties, and porosity of CMF/CNF pre-treated with silicates have reported promising results. The application of CMF/CNF pretreated with calcium and magnesium silicates in cardboard coating resulted in packaging with low water vapor permeability and high ductility. Conclusion: Silicates interact well with cellulose surfaces, making them a promising material for the chemical pre-treatment of CMF/CNF. Furthermore, the modification by silicates could be an interesting strategy for expanding the use of CMF/CNF in the development of new products

Copy number variants prioritization after array-CGH analysis - a cohort of 1000 patients

Array-based comparative genomic hybridization has been assumed to be the first genetic test offered to detect genomic imbalances in patients with unexplained intellectual disability with or without dysmorphisms, multiple congenital anomalies, learning difficulties and autism spectrum disorders. Our study contributes to the genotype/phenotype correlation with the delineation of laboratory criteria which help to classify the different copy number variants (CNVs) detected. We clustered our findings into five classes ranging from an imbalance detected in a microdeletion/duplication syndrome region (class I) to imbalances that had previously been reported in normal subjects in the Database of Genomic Variants (DGV) and thus considered common variants (class IV).info:eu-repo/semantics/publishedVersio

Natural history of G ynaikothrips uzeli (Thysanoptera, Phlaeothripidae) in galls of Ficus benjamina (Rosales, Moraceae)

ABSTRACT Galls induced by thrips are simple structures when compared to those of other groups of arthropods, and little is known regarding many of their aspects. This study aimed to investigate aspects of the natural history of Gynaikothrips uzeli Zimmermann, 1900 in galls of Ficus benjamina L., 1753 using seasonal sampling (summer and winter). Twenty trees were sampled and divided into quadrants. From each of them, five galls were collected, forming a total of 400 galls per collection. Thrips showed greater abundance at higher temperatures (25.7°C) and no precipitation. Sex ratio was biased towards females (0.022 males per female), pointing to an inbred mating structure. Arthropod fauna associated with galls was more abundant (N=798) in winter, and it included representatives of the orders Hemiptera, Hymenoptera, Araneae, Coleoptera, Neuroptera, Psocoptera, Thysanoptera, Diptera and Blattodea

Structure-Function Analysis of STRUBBELIG, an Arabidopsis Atypical Receptor-Like Kinase Involved in Tissue Morphogenesis

Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis