Impact of KCNJ11 rs5219, UCP2 rs659366, and MTHFR rs1801133 Polymorphisms on Type 2 Diabetes: A Cross-Sectional Study

OBJECTIVEType 2 diabetes (T2D) is a multifactorial disease. Its occurrence and prognosis are affected by many genes, including KCNJ11, UCP2, and MTHFR. The objective of this study was to investigate the distribution of various variants of these genes and evaluate their contribution to the outcome of T2D.METHODS80 females with T2D and class I-II obesity in the age of 40-65 years old underwent a genetic study, a biochemical blood test, and indirect calorimetry.RESULTSCarriers of C/T and T/T genotypes of the MTHFR gene had higher levels of cholesterol and triglycerides and lower levels of vitamin B6 and folate. The T/T genotype of the UCP2 gene was associated with higher levels of glycated hemoglobin, pre- and postprandial glycemia and lipid oxidation rate, lower carbohydrate oxidation, and lower serum vitamin C levels.CONCLUSIONSGenotyping UCP2 and probably KCNJ11 may help to select the optimal antidiabetic therapy and improve disease prognosis, whereas the MTHFR gene may determine the need to monitor group B vitamin status and the risk of dyslipidemia.     

VEGF Pathways in the Lymphatics of Healthy and Diseased Heart

Cardiac lymphatic system is a rare focus of the modern cardiovascular research. Nevertheless, the growing body of evidence is depicting lymphatic endothelium as an important functional unit in healthy and diseased myocardium. Since the discovery of angiogenic VEGF‐A in 1983 and lymphangiogenic VEGF‐C in 1997, an increasing amount of knowledge has accumulated on the essential roles of VEGF ligands and receptors in physiological and pathological angiogenesis and lymphangiogenesis. Tissue adaptation to several stimuli such as hypoxia, pathogen invasion, degenerative process and inflammation often involves coordinated changes in both blood and lymphatic vessels. As lymphatic vessels are involved in the initiation and resolution of inflammation and regulation of tissue edema, VEGF family members may have important roles in myocardial lymphatics in healthy and in cardiac disease. We will review the properties of VEGF ligands and receptors concentrating on their lymphatic vessel effects first in normal myocardium and then in cardiac disease.     

Peritumoral Brain Edema in Meningiomas Depends on Aquaporin-4 Expression and Not on Tumor Grade,Tumor Volume,Cell Count,or Ki-67 Labeling Index

Purpose

The aim of this study was to investigate to which degree the peritumoral brain edema in patients with meningiomas depends on aquaporin-4 (AQP4) expression, tumor grade, tumor volume, Ki-67 expression, and cell count.

Procedures

Thirty-three patients (25 women, 8 men; mean age 56.6 ± 16.0 years) with an intracranial meningioma underwent a standardized magnetic resonance (MR) examination prior to surgical resection. Edema indices (EIs) and tumor volumes were measured on the MR images. Tumor grade was classified according to the World Health Organization, and the proliferation index was estimated on Ki-67 antigen-stained specimens. Tumor cell count was evaluated. Eighteen specimens were stained for AQP4 expressioon.

Results

Significant intergroup differences between AQP4 expression grades and EIs were observed (P = 0.03), and a positive correlation was detected between EIs and AQP4 expression grades (r = 0.54; P < 0.05). A ROC analysis with EI as a test variable revealed an AUC of 0.77 (95 % CI 0.55–0.99) for the prediction of a moderate-to-strong AQP4 expression. An EI ≥1.5 predicted a moderate-to-high AQP4 expression with a sensitivity of 77 % and a specificity of 60 %. EI values of 2.2 and 3.5 reached sensitivity/specificity values of 69/80 % and 54/100 %, respectively. The AQP4 expression did not show any significant correlations with tumor grading, tumor volume, Ki-67 expression, or cell count. Moreover, we observed no significant positive or negative correlations between the EI and tumor grading (P = 0.7), tumor volume (P = 0.19), Ki-67 index (P = 0.9), and cell count (P = 0.34).

Conclusion

Peritumoral brain edema in patients with meningiomas may depend on AQP4 expression grades and not on tumor grade, tumor volume, Ki-67 expression, and cell count. The amount of edema predicted AQP4 expressions with moderate-to-good sensitivity and specificity.

     

Pancreatic adenocarcinoma: Outstanding problems

Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%.Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma.About 40% of patients have locally advanced nonresectable disease.In the past,determination of pancreatic cancer resectability was made at surgical exploration.The development of modern imaging techniques has allowed preoperative staging of patients.Institutions disagree about the criteria used to classify patients.Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis.There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition ofborderline resectable pancreatic cancer is also lacking.Thus,there is much room for improvement in all aspects of treatment for pancreatic cancer.Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer.With improved surgical techniques and advanced perioperative management,vascular resection and reconstruction are performed more frequently;patients thought once to be unresectable are undergoing radical surgery.However,when attempting heroic surgery,a realistic approach concerning the patient’s age and health status,probability of recovery after surgery,perioperative morbidity and mortality and life quality after tumor resection is necessary.     

Primary culture of mouse embryonic spinal cord neurons: cell composition and suitability for axonal regeneration studies

Objective: Primary culture is an effective experimental model to study molecular mechanisms that drive axonal regeneration after central nervous system injury. However, the culture of spinal cord (SC) cells remains poorly characterized. Here, we have analyzed the cell composition of a primary SC culture during its maturation.

Methods: Primary cell culture was prepared from mouse embryo spinal cords. After 2, 7, and 14 days of cultivation, the cells were fixed and stained with antibodies against β3-tubulin, nestin, crmp1, SMI-32, DCC or GFAP. We counted percentage of cells positive for the mentioned markers and measured the length of cell processes.

Results: We found that β3-tubulin and nestin were both expressed at day 2 of culture in vitro. Surprisingly (given the use of differentiation-supporting culture medium), the number of nestin+ cells has significantly increased during the first week of cultivation. The GFAP+ cells appeared only at the seventh day in vitro, and their fraction increased during the following cultivation. At 14 day in vitro, SC culture contained cells that expressed the markers typical of commissural and motor neurons. At this age, the neurons had the ability to repair injured neurites after mechanical damage.

Conclusion: Primary culture of SC cells is a dynamically developing cell population that contains all main types of SC cells and is capable of self-repair. Therefore, the culture of mouse embryonic SC cells represents an adequate experimental model for studying cellular and molecular processes taking place in SC neurons after axonal damage in the absence of external inhibitors.     

A phase Ib,open label,dose escalation trial of the anti-CD37 monoclonal antibody,BI 836826, in combination with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia

Investigational New Drugs - BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a transmembrane protein expressed on normal and malignant B cells. This open-label, phase Ib,...     

The endothelium-protective effect of 3-methyl-1,2,4-triazolyl-5-thioacetate (S)-2,6-diaminohexanic acid (lysinium): Effects on the expression of vascular endothelial growth factor (VEGF) and the characteristics of the endotheliocytes of the cerebral vessels of animals with cerebral ischemia

We modeled acute disruption of the brain blood circulation (ADBC) by bilateral ligature of the common carotids in white outbred rats. This resulted in the formation of endothelial dysfunction of capillary network in the IV–V layers of the cortex and the vessels of the pia mater, choroids plexuses, and the branches of the middle cerebral and ophthalmic arteries, which was seen as a considerable decrease in the density of nuclei of endotheliocytes, a decrease in the RNA concentration in them, expression of vascular endothelial growth factor (VEGF), and a substantial decrease in the index of the proliferative activity of endotheliocytes. Intraperitoneal treatment of rats with ADBC with lysinium for 21 days at a dose of 50 mg/kg led on the 4th day to an increase in the density of endotheliocytes in the capillary network of the brain cortex and the walls of cerebral vessels and an increase in the RNA content in endothelial nuclei. At the end of the lysinium treatment, we observed an increase in the density of endotheliocytes in the capillary network of the brain cortex and the walls of cerebral vessels, an increase in the RNA content in nuclei of endotheliocytes, and an increase in the density of proliferating endotheliocytes in these vessels, which was associated with increased VEGF concentration. Administration of the control drug piracetam had no endothelium-protective effect.