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[Effect of vitamin D3 and carbostimulin on the content of carbohydrate metabolism substrates and the tricarboxylic acid cycle in liver of rats with experimental rachitis].

The development of experimental rhachitis in rats is accompanied by a decrease in the dihydroxyacetonephosphate, glyceraldehyde-phosphate concentrations and by an increase in pyruvate, lactate, alpha-ketoglutarate, glutamate, oxalacetate and malate in the liver tissue. The feeding of vitamin D3 and carbostimulin normalizes, in the main, the concentrations of these metabolites.

Animals↗

Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese.

The present findings provide experimental evidence for the hypothesis that an impairment of mitochondrial function may be involved in manganese neurotoxicity. Specifically, the treatment of dopaminergic neuronal-derived cell line (PC12) with MnCl2 produced a significant inhibition of some mitochondrial complexes of the respiratory chain, while in the glial-derived cell line (C6) this effect was not observed. In PC12 the decrease in complex I activity was more pronounce than in other mitochondrial complexes. However treatment of cells with ZnSO4 exerted no significant variations in enzymatic activities. A direct exposure of mitochondrial fraction to MnCl2 reduced enzymatic activities of mitochondria in both cell lines adding further support to the proposed theory that the different sensitivity of the cells to manganese may be explained by a difference in uptake or intracellular storage. These data indicate that manganese neurotoxicity could be the result of a direct effect just on complex I activity or due to a secondary effect of oxidative stress induced by an excess of this transition metal.

Animals↗

Zinc benzoate, a contaminating environmental compound derived from polystyrene resin inhibits A-type monoamine oxidase.

The contaminants in deionized and distilled water (DDI water) boiled with polystyrene resin inhibited A-type monoamine oxidase (MAO, MAO-A preferentially deaminates serotonin and norepinephrine and regulates these amines concentration) activity in monkey brain mitochondria. To identify these contaminants, we attempted measurements by HPLC, FT-IR and NMR. The compound inhibiting MAO-A activity was zinc benzoate. Although it potently inhibited MAO-A activity, zinc benzoate did not effect MAO-B in monkey brain mitochondria. It also reversibly and competitively inhibited MAO-A activity in a dose-dependent manner. Zinc benzoate, however, did not inhibit either MAO-A or -B activities in rat brain mitochondria. These results indicate that zinc benzoate, which inhibits MAO-A activity, is easily incorporated in DDI water by boiling polystyrene and also may be a contaminating environmental chemical compound that alters the levels of serotonin and norepinephrine in the central nervous system.

Animals↗

Comparison of two peri-wound skin protectants in venous leg ulcers: a randomised controlled trial.

OBJECTIVE: A randomised controlled trial was designed to determine whether or not early intervention with a suitable skin barrier preparation could prevent skin breakdown. This study was conducted to compare the efficacy and cost-effectivenss of two skin protectants, Cavilon No Sting Barrier Film (NSBF) (3M Health Care) and zinc paste compound, in the management of maceration and irritation of the peri-wound area of venous leg ulcers. METHOD: Thirty-five patients with venous leg ulcers and surrounding skin problems were randomised to receive either NSBF or zinc paste compound. The preparation was then applied at each dressing change for 12 weeks. All patients had been receiving compression bandaging before entering the study and continued wearing it throughout the 12-week study period. RESULTS: The decrease in wound area was 5.11+/-8.39cm2 in the NSBF group and 4.59+/-5.83cm2 in the zinc paste group. The healing rate was 0.046cm per week with NSBF and 0.039cm per week with zinc paste. There was a significant difference in the time required to remove and re-apply the skin protectants: an average of 0.19 (+/-0.17) minutes in the NSBF group and 5.53 (+/-2.10) minutes in the zinc paste group (p<0.0001). CONCLUSION: Both products were effective barrier preparations. However, NSBF was easy to apply and transparent. The zinc paste was messy to apply and difficult to remove, and thus took up considerably more nursing time than NSBF. DECLARATION OF INTEREST: This study was supported by 3M Health Care.

Aged↗

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds.

Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype arenavirus species Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unable to perform viral RNA replication. Furthermore, in inactivated virions, the electrophoretic profile of the Z protein was altered when analysed under non-reducing conditions, whereas the patterns of the proteins NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with the virucidal agents induced unfolding and oligomerization of Z to high-molecular-mass aggregates, probably due to metal-ion ejection and the formation of intermolecular disulfide bonds through the cysteine residues of the Z RING finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells without affecting other cellular RING-motif proteins, such as the promyelocytic leukaemia protein PML. Altogether, the investigations described here illustrate the potential of the Z protein as a promising target for therapy and the prospects of the Z-reactive compounds to prevent arenavirus dissemination.

Animals↗

Notes on the application of microwaves for antigen retrieval in paraffin and plastic tissue sections.

In formalin-fixed, paraffin-embedded tissue enhanced or de novo immunostaining can be obtained by microwave boiling of sections in a metal salt or buffer solution. In this paper this new technique is reviewed and important factors influencing final results are discussed. Microwave antigen retrieval can also be applied for immunohistochemistry on plastic GMA sections. Here the action of the microwave method is probably mainly due to breaking the bonds between GMA and proteins prohibiting immunostaining. The microwave methods do not require trypsin treatment.

Aluminum Chloride↗

Analogues of Zinpyr-1 provide insight into the mechanism of zinc sensing.

Three compounds structurally related to the fluorescent zinc sensor Zinpyr-1 (ZP1) have been synthesized and characterized. In each of these ZinAlkylPyr (ZAP) analogues, an alkyl group (methyl, benzyl) replaces one of the metal-binding picolyl moieties in ZP1. The methyl-for-picolyl substitutions in ZAP1 and ZAP2 have a negligible effect on the optical spectrum of the fluorophore but elevate the quantum yields (Phi = 0.82 (ZAP1), 0.74 (ZAP2)) to values near that of Zn2+-saturated ZP1 (Phi = 0.92). The benzyl-for-picolyl substitution in ZAP3 similarly enhances the quantum yield (Phi = 0.52) relative to that of metal-free ZP1 (Phi = 0.38). As previously observed for methylated ZP1 sensors, methylation of the 6-position of the pyridyl ring diminishes the emission by lowering both the molar extinction coefficient and the quantum yield. Although these new ZAP compounds cannot detect Zn2+ fluorimetrically at neutral pH, complexation of Zn2+ does occur, as evidenced by sizable changes in the optical spectra. The ZAP1-3 probes can detect Zn2+ fluorimetrically at pH 9, indicating that proton-induced background emission obscures any Zn2+-induced fluorescence at pH 7. The tertiary amine groups in ZAP1-3 are less basic than those in ZP1, which implies that the additional pyridine rings are responsible for the emissive response to Zn2+ at pH 7.0.

Fluoresceins↗