Morphological and functional alterations in adult boar epididymis: Effects of prenatal and postnatal administration of flutamide

Background  

The dynamic cross-talk between epididymal cells is hormonally regulated and, in part, through direct cell-to-cell interactions. To date, no information is available regarding possible impact of anti-androgens on the proteins involved in the gap junctional communication within the boar epididymis. Thus, a question arised whether prenatal or postnatal exposure to an anti-androgen flutamide alters the expression of gap junction protein - connexin43 (Cx43) and androgen receptor (AR) expression in the caput, corpus and cauda epididymis and leads to delayed effects on morphology and function of adult pig epididymis.     

Effect of S-methylmethionine on the photosynthesis in maize at different chilling temperatures

The effect of the natural compound S-methylmethionine (SMM) on the functioning of the photosynthetic apparatus, the efficiency of photosynthesis and the synthesis of stress-induced phenoloids and anthocyanins involved in defence was investigated in young maize plants exposed to moderate and severe chilling stress. Damage to PSII was observed as a reduction in the value of variable fluorescence (Fv/Fm) which could be detected even after few hours of mild chilling stress. At temperatures below 10°C, the reduction in Fv/Fm was more pronounced. Changes in the value of net photosynthesis exhibited a similar tendency. SMM has a moderating effect on this reduction and its protective effect was more pronounced under long-lasting chilling stress and at the lowest temperatures. Monitoring of fluorescence intensities and ratios correlated with the levels of stress defence compounds. The fluorescence intensities were found to increase over the course of chilling stress in response to SMM, with the highest values being recorded in plants exposed to the longest period of stress. A similar tendency was observed for the quantity of anthocyanins. The results confirm the complex role of SMM, which is manifested both in preserving the ability of the photosynthetic apparatus to function and in stimulating the synthesis of metabolites involved in stress defence.     

Vision First? The Development of Primary Visual Cortical Networks Is More Rapid Than the Development of Primary Motor Networks in Humans

The development of cortical functions and the capacity of the mature brain to learn are largely determined by the establishment and maintenance of neocortical networks. Here we address the human development of long-range connectivity in primary visual and motor cortices, using well-established behavioral measures--a Contour Integration test and a Finger-tapping task--that have been shown to be related to these specific primary areas, and the long-range neural connectivity within those. Possible confounding factors, such as different task requirements (complexity, cognitive load) are eliminated by using these tasks in a learning paradigm. We find that there is a temporal lag between the developmental timing of primary sensory vs. motor areas with an advantage of visual development; we also confirm that human development is very slow in both cases, and that there is a retained capacity for practice induced plastic changes in adults. This pattern of results seems to point to human-specific development of the "canonical circuits" of primary sensory and motor cortices, probably reflecting the ecological requirements of human life.     

Interactions of 2,6-substituted purines with purine nucleoside phosphorylase from Helicobacter pylori in solution and in the crystal,and the effects of these compounds on cell cultures of this bacterium

Helicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible new drug target, by characterising its interactions with 2- and/or 6-substituted purines as well as the effect of these compounds on bacterial growth. Inhibition constants are in the micromolar range, the lowest being that of 6-benzylthio-2-chloropurine. This compound also inhibits H. pylori 26695 growth at the lowest concentration. X-ray structures of the complexes of PNP with the investigated compounds allowed the identification of interactions of inhibitors in the enzyme’s base-binding site and the suggestion of structures that could bind to the enzyme more tightly. Our findings prove the potential of PNP inhibitors in the design of drugs against H. pylori.     

Pharmacokinetics of propetamphos following intravenous administration in the F344 rat

Propetamphos [(E)-l-methylethyl 3[[(ethylamino)methoxyphosphinothioyl]oxy]-2-bu-tenoate], the active ingredient in Safrotin,® is an organophosphate developed by Sandoz, Ltd.® (Switzerland) as an insecticide (1). Although metabolism of propetamphos has been previously investigated (2,3), there is no pharmacokinetic data available in the literature. The current studies were undertaken to investigate the pharmacokinetics of propetamphos following intravenous administration in male and female Fischer 344 (F344) rats. Rats were dosed via an indwelling jugular cannula at a dose of 12 mg/kg (one-tenth the oral LD-50). Blood samples were withdrawn via the cannula at predetermined timepoints to quantitate plasma concentrations of propetamphos over time. Propetamphos is highly bound to plasma proteins (free fraction = 0.06). Free propetamphos concentration in plasma vs. time data were analyzed by noncompartmental methods. The terminal elimination rate constant, λ, was significantly different for males versus females (0.015 min^?1 for males and 0.037 min^?1 for females, p = 0.001). Plasma was cleared of unbound propetamphos at rates of 0.559 ± 0.069 and 0.828 ± 0.181 L/min/kg for males and females (mean ± standard error). Mean residence times (MRTs) for propetamphos in the body for males and females were 28.3 ± 5.7 and 14.4 ± 3.5 min, and the volume of distribution at steady state (Vss) was 14.7 ± 2.6 and 12.3 ± 4.5 L/kg. The differences in these parameters, clearance (CI), MRT, and Vss, were not statistically significant at the p < 0.05 level for males versus females, but MRT was nearly significantly different (p = 0.08). Because of the rapid elimination of propetamphos from plasma following intravenous administration, it is unlikely that propetamphos would bioaccumulate in environmentally exposed animals. Although the pharmacokinetic parameters were not statistically different for males and females in these studies, there was a clear clinical difference in their susceptibility to propetamphos toxicity. Female rats presented with overt signs of organophosphate intoxication, whereas males were only slightly effected. The observed gender-related clinical difference in susceptibility to toxicity suggests that there may be a difference in the extent of elimination due to activation versus detoxication of propetamphos in males and females. Another possible explanation for the clinical difference in propetamphos toxicity is that inhibition of acetyl-cholinesterase by the activated, oxygenated form of propetamphos (propetamphos oxon) may be greater in females than in males.     

Kinetics, molecular basis, and differentiation of L-lactate transport in spermatogenic cells

Round spermatid energy metabolism is closely dependent on the presence of L-lactate in the external medium. This L-lactate has been proposed to be supplied by Sertoli cells in the seminiferous tubules. L-Lactate, in conjunction with glucose, modulates intracellular Ca²⁺ concentration in round spermatids and pachytene spermatocytes. In spite of this central role of L-lactate in spermatogenic cell physiology, the mechanism of L-lactate transport, as well as possible differentiation during spermatogenesis, has not been studied in these cells. By measuring radioactive L-lactate transport and intracellular pH (pH_i) changes with pH_i fluorescent probes, we show that these cells transport L-lactate using monocarboxylate-H⁺ transport (MCT) systems. RT-PCR, in situ mRNA hybridization, and immunocyto- and immunohistochemistry data show that pachytene spermatocytes express mainly the MCT1 and MCT4 isoforms of the transporter (intermediate- and low-affinity transporters, respectively), while round spermatids, besides MCT1 and MCT4, also show expression of the MCT2 isoform (high-affinity transporter). These molecular data are consistent with the kinetic data of L-lactate transport in these cells demonstrating at least two transport components for L-lactate. These separate transport components reflect the ability of these cells to switch between the generation of glycolytic L-lactate in the presence of external glucose and the use of L-lactate when this substrate is available in the external environment. The supply of these substrates is regulated by the hormonal control of Sertoli cell glycolytic activity. cell differentiation; seminiferous tubules; spermatogenesis; testicle; meiosis     

Improvement of catalytic properties of Escherichia coli penicillin G acylase immobilized on glyoxyl agarose by addition of a six-amino-acid tag

A tag of three lysines alternating with three glycines was added to the C-terminal end of the beta chain of penicillin G acylase (PGA). This modification improved the immobilization efficiency of PGA on glyoxyl agarose and the catalytic properties of the PGA derivative, although it impaired the posttranslational steps of overexpressed protein maturation.