The effects of biological rhythms and sleep quality on benign paroxysmal positional vertigo and reflux symptom severity

Recently, there has been increased interest in chronotypes and clinical differences between them. However, there is limited information about the potential influence of the chronotypes on clinical manifestations and symptom intensity of somatic diseases. The aim of this study is to evaluate the impact of biological rhythm differences and sleep quality on benign paroxysmal positional vertigo (BPPV) and larengo pharyngeal reflux (LPR) severity. Forty-four LPR patients, 43 BBPV patients and 42 controls were included in the study. The morningness–eveningness questionnaire was used to determine chronotypes, and the Pittsburgh Sleep Quality Index was used to assess subjective sleep quality. Both patient groups reported a significantly greater tendency to eveningness diurnal preferences compared to healthy controls. As with the circadian preferences, patients with BPPV or LPR characterized by poorer sleep quality and worse insomnia than non-patient individuals. It can be concluded that the circadian rhythm and sleep quality are related to the severity of LPR and BPPV.     

Oral vitamin C and E combination modulates blood lipid peroxidation and antioxidant vitamin levels in maximal exercising basketball players

Oxidative stress occurs during maximal exercise, perhaps as a result of increased consumption of oxygen. Vitamins C and E can overcome the effects of antioxidants in exercise. We investigated the effects of supplementation with a combination of vitamin C and E (VCE) on blood lipid peroxidation (LP) and antioxidant levels following maximal training in basketball players. Blood samples were taken from 14 players (group A) and divided into two subgroups namely maximal training (group B) and maximal training plus VCE groups (group C). Group B maximally exercised for 35 days. VCE was supplemented to group C for 35 days and blood samples were taken from group B and C. Plasma and hemolyzed erythrocyte samples were obtained from the players. Erythrocyte glutathione peroxidase (GSH‐Px) activity and plasma vitamin E concentration were lower in group B than in group A, whereas plasma and erythrocyte LP levels were higher in group B than in group A. Plasma vitamin A, vitamin E, erythrocyte GSH‐Px, and reduced glutathione (GSH) values were higher in group C than in groups A and B although LP levels in plasma and erythrocytes were lower in group C than in group A and B. β‐Carotene values did not change in the three groups. In conclusion, VCE supplementation in maximal exercising basketball players may strengthen the antioxidant defense system by decreasing reactive oxygen species (ROS). Copyright © 2010 John Wiley & Sons, Ltd.     

Protein kinase D inhibits plasma membrane Na+/H+ exchanger activity

The regulation of plasma membraneNa⁺/H⁺exchanger (NHE) activity by protein kinase D (PKD), a novel proteinkinase C- and phorbol ester-regulated kinase, was investigated. Todetermine the effect of PKD on NHE activity in vivo, intracellular pH(pH_i) measurements were made inCOS-7 cells by microepifluorescence using the pH indicator cSNARF-1.Cells were transfected with empty vector (control), wild-type PKD, orits kinase-deficient mutant PKD-K618M, together with green fluorescentprotein (GFP). NHE activity, as reflected by the rate of acid efflux(J_H), wasdetermined in single GFP-positive cells following intracellularacidification. Overexpression of wild-type PKD had no significanteffect on J_H(3.48 ± 0.25 vs. 3.78 ± 0.24 mM/min in control atpH_i 7.0). In contrast,overexpression of PKD-K618M increasedJ_H (5.31 ± 0.57 mM/min at pH_i 7.0;P < 0.05 vs. control). Transfectionwith these constructs produced similar effects also in A-10 cells,indicating that native PKD may have an inhibitory effect on NHE in bothcell types, which is relieved by a dominant-negative action ofPKD-K618M. Exposure of COS-7 cells to phorbol ester significantlyincreased J_H in control cells but failed to do so in cells overexpressing either wild-type PKD (due to inhibition by the overexpressed PKD) or PKD-K618M(because basal J_Hwas already near maximal). A fusion protein containing the cytosolicregulatory domain (amino acids 637-815) of NHE1 (the ubiquitousNHE isoform) was phosphorylated in vitro by wild-type PKD, but with lowstoichiometry. These data suggest that PKD inhibits NHE activity,probably through an indirect mechanism, and represents a novel pathwayin the regulation of the exchanger.

     

In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones—Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles

The 1,2,4‐triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti‐inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1‐M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC₅₀ values lower than 10 µM concentrations. The low IC ₅₀ values of the compounds are M1 (3.88 µM), M2 (2.18 µM), M3 (4.2 µM), M4 (2.58 µM), M5 (2.88 µM), M6 (2.37 µM), M7 (3.49 µM), M8 (4.01 µM), M9 (8.90 µM), and M10 (3.12 µM).     

Identifying Statistical Dependence in Genomic Sequences via Mutual Information Estimates

Questions of understanding and quantifying the representation and amount of information in organisms have become a central part of biological research, as they potentially hold the key to fundamental advances. In this paper, we demonstrate the use of information-theoretic tools for the task of identifying segments of biomolecules (DNA or RNA) that are statistically correlated. We develop a precise and reliable methodology, based on the notion of mutual information, for finding and extracting statistical as well as structural dependencies. A simple threshold function is defined, and its use in quantifying the level of significance of dependencies between biological segments is explored. These tools are used in two specific applications. First, they are used for the identification of correlations between different parts of the maize zmSRp32 gene. There, we find significant dependencies between the untranslated region in zmSRp32 and its alternatively spliced exons. This observation may indicate the presence of as-yet unknown alternative splicing mechanisms or structural scaffolds. Second, using data from the FBI''s combined DNA index system (CODIS), we demonstrate that our approach is particularly well suited for the problem of discovering short tandem repeats—an application of importance in genetic profiling.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]     

Thermal tolerance of Litopenaeus vannamei (Crustacea: Penaeidae) acclimated to four temperatures

Critical thermal minima (CTMin) and maxima (CTMax) values were determined for the Pacific white shrimp Litopenaeus vannamei post-larvae and juveniles at four different acclimation temperatures (15, 20, 25, and 30 °C). The CTMin of shrimp at these acclimation temperatures were 7.82, 8.95, 9.80, and 10.96 °C for post-larvae and 7.50, 8.20, 10.20, and 10.80 °C for juveniles, respectively, at 1 °C h⁻¹ cooling rate. The CTMax values were 35.65, 38.13, 39.91, and 42.00 °C for post-larvae and 35.94, 38.65, 40.30, and 42.20 °C for juveniles at the respective acclimation temperatures. Both acclimation temperature and size of the shrimp affected CTMin values of L. vannamei (P<0.01). Overall, juveniles displayed significantly lower CTMin values than the post-larvae (P<0.0001). However, the CTMax response by post-larvae and juveniles were not significantly different from each other and no interaction was determined between the acclimation temperature and development stage (P>0.01). The area of the thermal tolerance polygon over four acclimation temperatures (15, 20, 25, and 30 °C) for the post-larvae of L. vannamei was calculated to be 434.94 °C². The acclimation response ratio (ARR) values were high ranging from 0.35 to 0.44 for both post-larvae and juveniles. L. vannamei appears to be more sensitive to low temperatures than other penaeid species and its cold tolerance zone ranged from 7.5 to 11 °C. In successful aquaculture temperature must never fall below 12 °C to prevent mortalities. Upper thermal tolerance is less of a problem as in most subtropical regions maximum water temperature rarely exceeds 34 °C, but care should be given if shallow ponds with low water renewal rate are being used.     

Antiangiogenic activity of 2-deoxy-D-glucose

Background

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.

Methodology/Principal Findings

In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG''s ability to interfere with endothelial N-linked glycosylation. 2-DG''s effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG''s effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH_BETAT_AG transgenic retinoblastoma model.

Conclusions/Significance

In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies.