Plasma Levels of Zinc,Copper, Copper/Zinc Ratio,and Activity of Carbonic Anhydrase in Equine Piroplasmosis

We have determined the plasma concentrations of copper, zinc, copper/zinc ratio, and carbonic anhydrase activity in horses infected with Babesia equi. The study was conducted in 14 horses with the disease and 10 healthy animals that served as controls. The infection was confirmed by the clinical manifestations of the disease and by Giemsa staining of thin blood smears showing the parasites inside red blood cells. The horses with piroplasmosis had lower plasma levels of zinc, elevated copper, and increased activity of carbonic anhydrase. Consequently, the copper/zinc ratio was also higher than in the healthy controls.     

Conducting-state properties of the KcsA potassium channel from molecular and Brownian dynamics simulations.

The mechanisms underlying transport of ions across the potassium channel are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We first build open-state configurations of the channel with molecular dynamics simulations, by pulling the transmembrane helices outward until the channel attains the desired interior radius. To gain insights into ion permeation, we construct potential energy profiles experienced by an ion traversing the channel in the presence of other resident ions. These profiles reveal that in the absence of an applied field the channel accommodates three potassium ions in a stable equilibrium, two in the selectivity filter and one in the central cavity. In the presence of a driving potential, this three-ion state becomes unstable, and ion permeation across the channel is observed. These qualitative explanations are confirmed by the results of three-dimensional Brownian dynamics simulations. We find that the channel conducts when the ionizable residues near the extracellular entrance are fully charged and those near the intracellular side are partially charged. The conductance increases steeply as the radius of the intracellular mouth of the channel is increased from 2 A to 5 A. Our simulation results reproduce several experimental observations, including the current-voltage curves, conductance-concentration relationships, and outward rectification of currents.     

Molecular dynamics simulations of membrane proteins

Membrane proteins control the traffic across cell membranes and thereby play an essential role in cell function from transport of various solutes to immune response via molecular recognition. Because it is very difficult to determine the structures of membrane proteins experimentally, computational methods have been increasingly used to study their structure and function. Here we focus on two classes of membrane proteins—ion channels and transporters—which are responsible for the generation of action potentials in nerves, muscles, and other excitable cells. We describe how computational methods have been used to construct models for these proteins and to study the transport mechanism. The main computational tool is the molecular dynamics (MD) simulation, which can be used for everything from refinement of protein structures to free energy calculations of transport processes. We illustrate with specific examples from gramicidin and potassium channels and aspartate transporters how the function of these membrane proteins can be investigated using MD simulations.     

Ion channels: recent progress and prospects

Determination of the crystal structure of the KcsA potassium channel and its subsequent refinement at 2 A resolution have stimulated much interest in modelling of ion channels. Here we review the recent developments in ion channels research, focusing especially on the question of structure-function relationships, and discuss how permeation models based on Brownian and molecular dynamics simulations can be used fruitfully in this endeavour.     

Comparison of oxidative stress and antioxidant capacity before and after running exercises in both sexes

Background: It has been difficult to determine, from the published literature, whether men or women have higher levels of exercise-induced oxidative stress.Objective: The aim of this study was to compare variations between the sexes in lipid hydroperoxide (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and lactate dehydrogenase (LDH) after 3 different running exercises performed at the same speed.Methods: Eligible participants were healthy university students of both sexes. The participants performed running exercise tests at distances of 800, 1500, and 3000 m at a speed of 10 km/h. Blood samples were taken from the participants just before and immediately after the running activities to determine LPO, SOD, CAT, GR, and LDH, and these measures were compared both before and after exercise and between the sexes.Results: A total of 17 young and healthy, but not physically trained, students (n = 8 men; mean age, 22.00 years; n = 9 women; mean age, 21.78 years) participated in this study. Height, weight, and maximum oxygen consumption values were significantly higher in men than in women (P = 0.01). Significant gender effects were found in LPO levels at 3000 m (F = 5.51; P = 0.03) and in SOD activity at 800 m (F = 7.92; P = 0.01) and 3000 m (F = 6.05; P = 0.03). CAT activity also differed between the sexes at 800 m (F = 15.67; P = 0.01) and 1500 m (F = 6.55; P = 0.02). However, no significant gender-time interaction effect was observed for any measurement at the 800-, 1500-, and 3000-m distances.Conclusions: Changes in LPO, SOD, and CAT activities at different running distances were not different between men and women over time because of a nonsignificant gender-time interaction. With regard to changes in oxidative stress, men and women had similar responses to exercise at the same absolute workload, despite significant differences in physical characteristics.     

Aromatase in endometriosis and uterine leiomyomata

Endometrial tissue from uterine disease-free women does not exhibit aromatase activity. In contrast, aromatase enzyme activity and mRNA levels are readily detectable in endometriosis. PGE₂ stimulates both aromatase expression and activity in endometriotic stromal cells via promoter II region of the aromatase gene. This results in local production of estradiol, which induces PGE₂ formation and establishes a positive feedback cycle. This mechanism seems to contribute to continuous production of estradiol and PGE₂. Aromatase mRNA levels and enzyme activity are also present in uterine leiomyomata that are estrogen-dependent benign tumors of the myometrium. Successful treatment of endometriosis and uterine leiomyomata using aromatase inhibitors by recent pilot trials underscores the clinical significance of these molecular studies.     

Expression of cell adhesion molecules in the adriamycin-induced esophageal atresia rat model

Cell adhesion molecules are well-known membrane glycoproteins widely expressed during embryonic development that play a crucial role in cell division, migration and differentiation. We investigated the cell-matrix relationship using N-CAM and pan-cadherin adhesion molecules in the adriamycin-induced esophageal atresia (EA) rat model in the hope of finding a clue to the mechanisms of this unique anomaly.Time-mated pregnant Sprague-Dawley rats were given either saline or adriamycin on days 8 and 9 of gestation. Embryos were harvested on the 18th day of gestation. Esophageal specimens obtained from adriamycin-exposed embryos with (EA+) or without esophageal atresia (EA-) and from saline-exposed embryos were immunostained with N-CAM and pan-cadherin primary antisera.The esophageal specimens from control and EA- groups revealed similar immunostaining properties: weak N-CAM and pan-cadherin immunoreactivity. In contrast, the EA+ group showed intense immunoreactivity.Our study demonstrated an increased synthesis of N-CAM and pan-cadherin in the epithelial cells of the atretic esophagus and trachea. These results suggest that embryonic cell-cell and cell-matrix interactions may play a crucial role in the development of adriamycin-induced EA.     

Youth and AIDS--a study of attitudes,knowledge, behavior and risks in the post-war Croatia

According to the latest reports, the Eastern Europe currently exhibits the greatest relative increase in the number of newly registered HIV infections in the world. At the same time, Central Europe remains relatively spared from the epidemic, with reported rates significantly lower than those in both Eastern and Western Europe. Croatia geographically affiliates to Central Europe, but it has two specific potential risk factors in comparison to neighboring countries: recent War events and a summer season when immigration of large number of tourists from Central and Eastern Europe is expected. Therefore, it is critical to examine AIDS attitudes in young people, increase their knowledge, monitor their behavior and warn on risks in order to prevent larger spread of epidemics from Eastern Europe to Croatia. In this study, we report on a large related survey and education program among 17-year-old high school pupils that was conducted in years immediately following the War (1996-1999).