Effect of vitamin D2 stimulation on amine stores and secretory granules in the calcitonin cells of the mouse

Summary The calcitonin-producing cells (C cells) of the thyroid gland are characterized by numerous suhmicroscopic granules, believed to contain the hormone, by a strong argyrophilia, and by the ability to synthesize and store certain arylethylamines (such as dopamine) from corresponding immediate precursors (such as DOPA).In mice, vitamin D₂ treatment—known to increase calcitonin secretion—evoked a degranulation and a loss of argyrophilia of the C cells, and a reduction in their content of dopamine (induced by exogenous DOPA). Additional treatment with a monoamine oxidase inhibitor restored the dopamine content of the C cells, although they were still degranulated. Treatment with reserpine, which inhibits the amine-storing mechanism, prevented the degranulation following vitamin D₂ treatment.The findings support the assumption that a functional rather than only a structural relationship exists between the intracellular amine and the secretory granules in cells elaborating calcitonin, and that the amine is involved in the secretion of the polypeptide hormone.     

Presynaptic regulation of dopaminergic transmission in the striatum

1. In vitro studies have indicated that several transmitters present in the striatum can regulate presynaptically the release of dopamine (DA) from nerve terminals of the nigrostriatal DA neurons. 2. The receptors involved in these local regulatory processes are located or not located on DA nerve terminals. 3. Recent in vivo investigations have demonstrated that the corticostriatal glutamatergic neurons facilitate presynaptically the release of DA and have allowed the analysis of the respective roles of presynaptic events and nerve activity in the control of DA transmission.     

Surface charges of the membrane and cell adhesion substances determine the structural integrity of hair bundles from the inner ear of fish

Summary The hairs (stereocilia = stereovilli) of sensory cells from the inner ear of vertebrates are interconnected by several types of connectors, whose role is unknown. They appear to stabilize the hair bundle mechanically, and may be directly involved in mechano-electric transduction. Our transmission electron-microscopical investigation of sensory epithelia from two species of fish (Rutilus rutilus, Scardinius erythrophthalmus, both Leuciscidae) has shown that not only the connectors but also the surface charges of the membrane are important factors for determining the shape of the hair bundle and the spatial interrelation of the stereovilli. A reduction of the ionic strength in the medium leads to an increase in distance between the stereovilli. This may be the result of an extension of the spread of the surface potential of the membrane at low ionic strength. The connectors are not broken by the increase in distance between the stereovilli. They are EDTA (ethylene-diamine-tetra-acetic-acid) resistant as are some cell adhesion molecules such as N-CAM (nerve-cell adhesion molecule) and protein A from Dictyostelium discoideum. The connectors do not prevent polycation-induced fusion of adjacent stereovillar membranes.     

Efectos del uso del 17 β-estradiol y la genisteína en la enfermedad de Alzheimer en mujeres con menopausia

The use of 17 β-estradiol and genistein in women with menopause helps in the reduction of vasomotor symptoms and cognitive improvement. There is evidence on the use of certain flavonoids such as genistein, which has a potentially neuroprotective role in neurodegenerative diseases such as Alzheimer's. Scientific evidence on the effects of phytoestrogens and genistein during menopause and their effect on cognition are scarce, however, in the present review it was found that the intervention with 17 β-estradiol has positive effects on cognition in women with Alzheimer's disease. In addition, the use of genistein, daidzein or any supplement based on isoflavones may influence vasomotor symptoms. 17 β-estradiol supplements in women in early menopause and with some degree of cognitive impairment may have beneficial effects.     

High-resolution electron microscopical study of cyst walls of Entamoeba spp

Knowledge of the fine structural organization, molecular composition and permeability properties of the cell surface of intestinal protozoan cysts is important to understand the biologic basis of their resistance. Recent studies on the biology of the cyst walls of Entamoeba histolytica and Entamoeba invadens have considerably advanced knowledge on the cellular processes involved in the transport and surface deposition of the main cyst wall components. Using transmission electron microscopy, cytochemistry, scanning electron microscopy and freeze-fracture techniques, we have obtained new information. In mature cysts the permeability of Entamoeba cysts is limited to small molecules not by the cyst wall, but by the plasma membrane, as demonstrated with the use of ruthenium red as an electron-dense tracer. Cell walls of E. histolytica cysts are made up of five to seven layers of unordered fibrils 7-8 nm thick. Alcian blue stains a regular mesh of fibrils approximately 4 nm thick, running perpendicularly to the cyst wall. In addition, abundant ionogenic groups are seen in cyst walls treated with cationized ferritin. In the mature cysts of E. histolytica and E. invadens small cytoplasmic vesicles with granular material were in close contact with the plasma membrane, suggesting a process of fusion and deposition of granular material to the cell wall. The plasma membrane of mature cysts is devoid of intramembrane particles when analyzed with the freeze-fracture technique. When viewed with scanning electron microscopy the surface of E. histolytica cysts clearly differs from that of Entamoeba coli and E. invadens.     

Venom of the crotaline snake Atropoides nummifer (jumping viper) from Guatemala and Honduras: comparative toxicological characterization,isolation of a myotoxic phospholipase A2 homologue and neutralization by two antivenoms

A comparative study was performed on the venoms of the crotaline snake Atropoides nummifer from Guatemala and Honduras. SDS-polyacrylamide gel electrophoresis, under reducing conditions, revealed a highly similar pattern of these venoms, and between them and the venom of the same species from Costa Rica. Similar patterns were also observed in ion-exchange chromatography on CM-Shephadex C-25, in which a highly basic myotoxic fraction was present. This fraction was devoid of phospholipase A₂ activity and strongly reacted, by enzyme-immunoassay, with an antiserum against Bothrops asper myotoxin II, a Lys-49 phospholipase A₂ homologue. A basic myotoxin of 16 kDa was isolated to homogeneity from the venom of A. nummifer from Honduras, showing amino acid composition and N-terminal sequence similar to those of Lys-49 phospholipase A₂ variants previously isolated from other crotaline snake venoms. Guatemalan and Honduran A. nummifer venoms have a qualitatively similar toxicological profile, characterized by: lethal; hemorrhagic; myotoxic; edema-forming; coagulant; and defibrinating activities, although there were significant quantitative variations in some of these activities between the two venoms. Neutralization of toxic activities by two commercially-available antivenoms in the region was studied. Polyvalent antivenom produced by Instituto Clodomiro Picado was effective in the neutralization of: lethal; hemorrhagic; myotoxic; coagulant; defibrinating; and phospholipase A₂ activities, but ineffective against edema-forming activity. On the other hand, MYN polyvalent antivenom neutralized: hemorrhagic; myotoxic; coagulant; defibrinating; and phospholipase A₂ activities, albeit with a lower potency than Instituto Clodomiro Picado antivenom. MYN antivenom failed to neutralize lethal and edema-forming activities of A. nummifer venoms.     

Polymorphism of the Y-chromosome diallelic loci in the ethnic populations of the Altai-Sayan region

Using the data on five biallellic Y-chromosome loci (DYS199, 92R7, SRY1532, RBF5 and DYS287) polymorphism, genetic structures of the five Turkic-speaking ethnic groups of the Altai-Sayan highland (Tuvinians, Sojots, Shorians, Khakassians, and Southern Altaians (Altai-Kizhi), were described. The gene pools of the populations examined were characterized by the presence of pronounced paleo-Caucasoid component (92R7-T-lineages). The frequency of this component increased westward, reaching more than 70% in Shorians and Southern Altaians. Haplotype TAT-C (RBF5 locus) was observed in all populations, except Shorians, with the frequencies varying from 5.4% in Altai-Kizhi to 18.8% in Khakassians. The Alu-insertion in the DYS287 locus was revealed only in the Altaian sample with the frequency of 3.3%. It was established that the Altai-Sayan populations studied split into two statistically significantly different groups. One of the groups was represented by Tuvinians, Sojots, and Khakassians, while another one was comprised of Shorians and Altaians.     

The Bacillus subtilis AddAB helicase/nuclease is regulated by its cognate Chi sequence in vitro

The AddAB enzyme is important to homologous DNA recombination in Bacillus subtilis, where it is thought to be the functional counterpart of the RecBCD enzyme of Escherichia coli. In vivo, AddAB responds to a specific five-nucleotide sequence (5'-AGCGG-3' or its complement) in a manner analogous to the response of the RecBCD enzyme to interaction with chi sequences. Here, we show that purified AddAB enzyme is able to load at a double-stranded DNA end and is both a DNA helicase and nuclease, whose combined action results in the degradation of both strands of the DNA duplex. During translocation, recognition of the properly oriented sequence 5'-AGCGG-3' causes attenuation of the AddAB enzyme nuclease activity that is responsible for degradation of the strand 3'-terminal at the entry site. Therefore, we conclude that 5'-AGCGG-3' is the B. subtilis Chi site and it is hereafter referred to as chi(Bs). After encountering chi(Bs), both the degradation of the 5'-terminal strand and the helicase activity persist. Thus, processing of a double-stranded DNA end by the AddAB enzyme produces a duplex DNA molecule with a protruding 3'-terminated single-stranded tail, a universal intermediate of the recombination process.     

Endothelial mitochondria--a novel target for pharmacology of endothelial dysfunction

Vascular endothelium the inside layer of the cardiovascular system is presently looked upon as an important paracrine, autocrine and endocrine organ that determines the health of the cardiovascular system. In fact, healthy endothelium is essential for homeostasis of cardiovascular system, while endothelial dyfunction leads to cardiovascular diseases including atherosclerosis, diabetes and heart failure. Endothelial dysfunction is tightly linked to the overproduction of reactive oxygen species, development of oxidant stress and inflammatory response of endothelium. Mitochondria of the vascular endothelium seem to be an important player in these processes. In contrast to numerous cell types, synthesis of ATP in endothelium occurs in major part via a glycolytic pathway and endothelium seem to be relatively independent of the mitochondrial pathway of energy supply. However, as evident from recent studies, mitochondrial pathways of free radicals production tighly linked to mitochondrial and cytosol changes in the ion homeostasis play an important role in the regulation of endothelial inflammatory response, in the development of oxidative stress and apoptosis of vascular endothelium. Therefore, endothelial mitochondria appears critical in the regulation of endothelial functions and represent a novel target in pharmacology of endothelial dysfunction in cardiovascular diseases.     

The mutagenicity and DNA-damaging activity of cyclic aliphatic sulfuric acid esters.

The cyclic aliphatic sulfuric acid esters 1,2-ethylene sulfate (ESF), 1,3-propylene sulfate (PSF) and 1,3-butylene sulfate (BSF) have been tested for their mutagenic and DNA-damaging activity. Mutagenicity of the compounds was established with his-auxotrophic indicator strains of Salmonella typhimurium using the in vitro plate test and the host-mediated assay technique with mice as host animals. The DNA-damaging activity was tested in a repair test with Proteus mirabilis mutants defective in DNA repair.In the repair test with a set of P. mirabilis strains (PG713 hcr^?rec^?: PG273 hcr⁺rec⁺) PSF and BSF showed a preferential growth inhibition of the repair-defective strain suggesting DNA-damaging activity of these chemicals. No such activity was found for ESF using the same concentrations of 5 and 15 μmol/plate.All cyclic sulfates revert the tester strain TA1535 of S. typhimurium in vitro indicating their ability to induce base substitutions. Compared with the reference compounds dimethyl sulfate (DMS), diethyl sulfate (DES), 1,3-propane sulfone (PPS) and 1,4-butane sulfone (BTS) the mutagenic activity in the plate test can be described as follows: PPS > PSF > BSF > BTS > ESF > DES > DMS.Dose-response studies in the host-mediated assay with tester strain TA1950 of S. typhimurium as genetic indicator system revealed a linear dosedependency of mutagenic activity. For PPS and PSF the lowest effective dose (LED) has been established as 10 μmol/kg. The LED for BSF and BTS was 50 μmol/kg, DMS and DES were mutagenic in doses of 2500 μmol/kg, while ESF was only weakly mutagenic with a LED of 5000 μmol/kg.The dose-response studies in the host-mediated assay and the results obtained in the in vitro spot test demonstrate similarities in the mutagenic action of the cyclic sulfates PSF and BSF and the respective sulfones, while the stronger alkylating compound ESF was a weak mutagen both in vitro and in vivo.