Effect of estradiol-17ß and prostaglandins on rat myometrial gap junctions

The effects of estradiol-17ß and indomethacin on myometrial gap junction development, plasma estradiol levels and uterine PGF_2α content were evaluated in immature and/or ovariectomized, mature rats. High doses of estradiol stimulated the development of gap junctions in the myometrium of animals from both groups. Concomitant injections of estradiol and indomethacin to ovariectomized rats potentiated the estradiol stimulation of gap junctions. Plama estradiol levels were lower in ovariectomized rats treated with both estradiol and indomethacin than in animals treated with estradiol alone. Indomethacin also enhanced the uptake and retention of ³H-estradiol into uterine tissues. Uterine PGF_2α content of ovarectomized rats was stimulated with the initial injection of estradiol but thereafter, the PGF_2α content declined with repeated injections to values lower than that observed in controls. Prostaglandin F_2α content in tissues from rats treated with estradiol plus indomethacin were also higher than that observed in rats treated with indomethacin alone, however, the values obtained in both groups were significantly lower compared to those from control animals. These results are consistent with the hypothesis that steroid hormones and prostaglandins regulate myometrial gap junction formation. Regulation of myometrial gap junctions by prostaglandins is discussed with respect to down regulation of the steroid-receptor mechanism and effects on cyclo-oxygenase or lipoxygenase products.     

Microbial transformation of primaquine by Candida tropicalis

The microbial metabolism of primaquine, a 6-methoxy-8-aminoquinoline antimalarial agent, was investigated. The yeast Candida tropicalis was found to convert primaquine to the previously reported N-acetylated derivative. On continued incubation of C. tropicalis in the presence of the N-acetylated derivative, a minor dimeric metabolite was formed. The proposed structure of the metabolite was based primarily on the analysis of its spectroscopic properties (1H and 13C nuclear magnetic resonance spectra and field-desorption mass spectrum). The structure of the metabolite was proven by direct comparison with an authentic sample of the minor dimeric metabolite prepared by treatment of the N-acetylated derivative with formaldehyde in the presence of formic acid in methanol.     

How Does It Kill?: Understanding the Candidacidal Mechanism of Salivary Histatin 5

Histatins are salivary cationic peptides that provide the first line of defense against oral candidiasis caused by Candida albicans. This minireview presents a critical evaluation of our knowledge of the candidacidal mechanism of histatin 5 (Hst 5). Hst 5 is the most potent among all histatin family members with regard to its antifungal activity. The mode of action of Hst 5 has been a subject of intense debate. Unlike other classical host innate immune proteins, pore formation or membrane lysis by Hst 5 has largely been disproven, and it is now known that all targets of Hst 5 are intracellular. Hst 5 binds C. albicans cell wall proteins (Ssa1/2) and glycans and is taken up by the cells through fungal polyamine transporters in an energy-dependent manner. Once inside the fungal cells, Hst 5 may affect mitochondrial functions and cause oxidative stress; however, the ultimate cause of cell death is by volume dysregulation and ion imbalance triggered by osmotic stress. Besides these diverse targets, a novel mechanism based on the metal binding abilities of Hst 5 is discussed. Finally, translational approaches for Hst 5, based on peptide design and synergy with other known drugs, are considered a step forward for bench-to-bed application of Hst 5.     

A comparison of narcotic analgesics with neuroleptics on behavioral measures of dopaminergic activity.

Because of many practical difficulties which are encountered in obtaining direct evidence for the involvement of brain neurotransmitters in the action of narcotic drugs, several indirect procedures are often employed. One such method is to compare on the same measures of drug action the narcotic drugs with a non-narcotic drug having a known mechanism of action. Haloperidol is a prototype non-narcotic drug which blocks dopamine receptors and many of its actions are believed to be associated with this receptor blockade. In this paper we compare various actions of haloperidol or other neuroleptics with morphine or other narcotic analgesics using the same testing parameters. We hope that such a comparison would evaluate the role of dopamine receptors in narcotic action and narcotic dependence. This discussion is limited only to the behavioral measures as a comparison of neurochemical measures was recently reviewed in another paper (1).     

Electroporation-Based Genetic Manipulation in Type I Methanotrophs

Methane is becoming a major candidate for a prominent carbon feedstock in the future, and the bioconversion of methane into valuable products has drawn increasing attention. To facilitate the use of methanotrophic organisms as industrial strains and accelerate our ability to metabolically engineer methanotrophs, simple and rapid genetic tools are needed. Electroporation is one such enabling tool, but to date it has not been successful in a group of methanotrophs of interest for the production of chemicals and fuels, the gammaproteobacterial (type I) methanotrophs. In this study, we developed electroporation techniques with a high transformation efficiency for three different type I methanotrophs: Methylomicrobium buryatense 5GB1C, Methylomonas sp. strain LW13, and Methylobacter tundripaludum 21/22. We further developed this technique in M. buryatense, a haloalkaliphilic aerobic methanotroph that demonstrates robust growth with a high carbon conversion efficiency and is well suited for industrial use for the bioconversion of methane. On the basis of the high transformation efficiency of M. buryatense, gene knockouts or integration of a foreign fragment into the chromosome can be easily achieved by direct electroporation of PCR-generated deletion or integration constructs. Moreover, site-specific recombination (FLP-FRT [FLP recombination target] recombination) and sacB counterselection systems were employed to perform marker-free manipulation, and two new antibiotics, zeocin and hygromycin, were validated to be antibiotic markers in this strain. Together, these tools facilitate the rapid genetic manipulation of M. buryatense and other type I methanotrophs, promoting the ability to perform fundamental research and industrial process development with these strains.     

Optical absorption investigations for efficient crystal violet dye removal from wastewater via carbon nanotubes:Montmorillonite-based nanocomposite

The current study reports a facile method to fabricate functionalized multi-walled carbon nanotubes and montmorillonite clay mineral-based nanocomposite matrix and its detailed characterization using spectroscopic and morphological techniques. The nanocomposites have been studied for their potential applications in the treatment of contaminated water using batch adsorption studies. The investigations conducted using optical absorption spectroscopic measurements for the adsorption process indicate that the nanocomposite matrix can effectively remove almost 98% of the dye from aqueous solution. The nanocomposites have showed fast and strong adsorption behaviour for the dye with the maximum adsorption capacity (q_m) of ~467.3 mg g⁻¹ in 25 min. The experimental data at equilibrium were also correlated with the theoretical adsorption isotherm and kinetic models. The results demonstrate that the experimental data fits well to the Freundlich adsorption isotherm model and conforms to second-order kinetics. Furthermore, the nanocomposite exhibits good recyclability without any marked decrease in the adsorption performance even after five adsorption cycles of usage which indicates its potential application as reusable adsorbent for the efficient removal of hazardous dyes from contaminated water.     

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted.     

Formation of some monopositive and dipositive carbonium ions in chlorosulphuric acid. Part XV

Tetraphenyl-p-xylene-glycol, tetraphenyl-phthalein and Dipheno(3-10′)thiazinyl are shown to form dipositive carbonium ions, but triphenyl acetic acid, 2-3-5-6 tetramethyl benzoic acid, 2-3-4-5-6 pentamethyl benzoic acid, tert-butyl alcohol, triphenyl carbinol, tri-p-tolyl carbinol, tri-o-tolyl carbinol, tri-p-chlorophenyl carbinol and tri-p-nitrophenyl carbinol form monopositive carbonium ions in chlorosulphuric acid, as revealed by conductometric and u.v. spectral studies. Oxalyl chloride decomposes while ethylene glycol is sulphonated in chlorosulphuric acid. Dichloroethane behaves as a non-electrolyte but dibromomethane disproportionates in this medium.