Voltammetric behavior of benznidazole at a DNA-electrochemical biosensor

Benznidazole is a drug used commonly as a therapeutic agent against Chagas' disease in Brazil. To clarify the cytotoxic action of benznidazole the electrochemical reduction of benznidazole has been investigated using a DNA-electrochemical biosensor, prepared by modification of a glassy carbon electrode with DNA, and the results compared with reduction at a bare glassy carbon electrode. The dependence of peak potential with pH follows slopes of 59 and 52 mV per pH unit in acid media, respectively, which corresponds to a mechanism involving the same number of electrons and protons. In neutral and alkaline solution no significant dependence of peak potential with pH was found. During the electrochemical reduction of benznidazole the formation of the hydroxylamine derivative occurs, involving a total of four electrons. The potentials for reduction were less negative when using the DNA-modified glassy carbon electrode than at the bare glassy carbon electrode although the mechanism was the same, and at pH 7.51 the peak current was four times higher than that obtained with the bare electrode. The DNA-biosensor enabled pre-concentration of the drug onto the electrode surface and the in situ damage caused to the DNA on the electrode surface by the product of benznidazole reduction could be detected electrochemically. The results are in agreement with the hypothesis that the hydroxylamine derivative is the reactive species responsible for the cytotoxic action of benznidazole.     

Chronic exposure of rats to cotton-mill-room noise changes the cell composition of the tracheal epithelium

The work environment of cotton mill rooms of modern textile plants is characterized by noise pollution. We have taped and reproduced this noisy environment to study its effects on experimentally exposed rats. Because we have previously documented that chronic noise causes alterations in the respiratory epithelium, we have focused our investigation on the morphology of the tracheal lining. Wistar rats were exposed to the textile-type noise from 1 up to 7 months, with an average 40 hours weekly exposure of the animals. The rats were sacrificed monthly and the tracheas were studied by scanning electron microscopy (SEM) to quantify the areas of the airway lining that were covered by ciliated, serous or other cells of the epithelium. We found that noise exposure of the rats caused a significant loss of tracheal ciliated cells; an increased density of serous cells on the epithelium balanced this change. This modification of the rat trachea was already established after 1 month of noise treatment of the animals; it did not change significantly throughout the 7-month course of the herein investigation. Loss of ciliated cells was more intense in areas of the tracheal epithelium located between the regions of cartilage rings. We conclude that the ciliated cell is an elective target for damage caused on the respiratory epithelium by the workplace noise occurring in cotton mill rooms. This modification of the respiratory epithelium is likely to impair clearance of the airways since this function depends on the activity of ciliated cells.     

Transducing system operated by adenosine A(2A) receptors to facilitate acetylcholine release in the rat hippocampus

In spite of the increasing evidence concerning its neurotoxicity, young human individuals are often involved in the recreational use of amphetamine-type stimulants such as 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). A study aimed to investigate short- and long-term consequences of a repeated and intermittent MDMA administration (0, 5 or 10 mg/kg i.p., 3 days treatment history) was conducted in mice. Mice were injected at different phases in development, namely at early (28 days old), middle (38 days old) or late (52 days old) adolescence. When assessed for nociceptive response, a dose-dependent analgesia was found in middle and late adolescent mice. Carryover consequences of previous MDMA treatment were then investigated at adulthood (80 days old). In a social interaction test, levels of environment exploration and social behaviour resulted markedly increased in drug-free state as a function of drug exposure during development, whereas others behaviours were reduced. MDMA challenge (5-mg/kg dose) produced the expected hyperactivity, as well as a marked increment of hypothalamic serotonin (5-hydroxyhyptamine, 5-HT) levels. Mice treated chronically with MDMA during middle and late adolescence were associated with important reductions of the indoleamine. As a whole, these results indicate a differential long-term vulnerability to behavioural and neurotoxicant effects of MDMA as a function of the developmental stage of exposure.     

Antihypertensive,vasodilator and antioxidant effects of a vinifera grape skin extract

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.     

Study of sterilizing effectivity of different ethylene oxide gaseous mixtures using CFCs and HCFCs (Oxyfume 12R and 2002R)

The use of ethylene oxide as a sterilizing agent has been frequently practiced, especially taking into account the huge variety of medical devices produced with heat sensitive materials. Mixtures of ethylene oxide and inert gases have been widely adopted in order to decrease the undesirable flammable and explosive properties of ethylene oxide. This article provides a study regarding the sterilizing effectiveness of two ethylene oxide blends: Oxyfume 2002R (using HCFCs 22 and 124) and Oxyfume 12R (using CFC 12), at different temperatures (45, 55, and 65 degrees C). To accomplish this procedure, sub-lethal challenges were performed (0, 3, 6, 9, 12, and 15 minutes) using biological indicators (obtained in the laboratory) made of Bacillus subtilis var. niger ATCC 9372. The sterilizing efficacy of both mixtures was equivalent at the gas concentration of 600 mg/L. The influence of higher temperatures was thus proved.     

Insulin affects synaptosomal GABA and glutamate transport under oxidative stress conditions

In this study, we investigated the in vitro effect of exogenously administered insulin on the susceptibility to oxidative stress and on the accumulation of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in a synaptosomal fraction isolated from male Wistar rat brain cortex. Insulin (1 microM) did not affect synaptosomal lipid peroxidation induced by the oxidant pair ascorbate/Fe(2+), although under these conditions an increase in thiobarbituric acid reactive substances (TBARS) levels was observed. Under control conditions, the presence of insulin did not change the uptake of [3H]GABA or [3H]glutamate. In contrast, under oxidizing conditions, we observed a 1.8- and a 2.2-fold decrease in [3H]GABA and [3H]glutamate accumulation, respectively, and insulin reverted the lower levels of both [3H]GABA and [3H]glutamate accumulation (to 86.74+/-6.26 and 67.01+/-6.65% of control, respectively). Insulin also increased the extrasynaptosomal levels of GABA and glutamate, determined both in control and oxidizing conditions. From this study, we can conclude that insulin is a modulator of amino acid neurotransmitter transport, either directly, as seems to occur under normal conditions, or via the decrease in ATP levels and the subsequent reversion of the amino acid transporters, as seems to occur under oxidative stress conditions. The modulation of both GABA and glutamate transport might be implicated in the neuroprotective role of insulin.     

Subcellular localization of adenosine A(1) receptors in nerve terminals and synapses of the rat hippocampus

Adenosine is a neuromodulator in the CNS that mainly acts through pre- and postsynaptic A(1) receptors to inhibit the release of excitatory neurotransmitters and NMDA receptor function. This might result from a highly localized distribution of A(1) receptors in the active zone and postsynaptic density of CNS synapses that we now investigated in the rat hippocampus. The binding density of the selective A(1) receptor antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), was enriched in membranes from Percoll-purified nerve terminals (B(max)=1839+/-52 fM/mg protein) compared to total membranes from the hippocampus (B(max)=984+/-31 fM/mg protein), the same occurring with A(1) receptor immunoreactivity. [3H]DPCPX binding occurred mainly to the plasma membrane rather than to intracellular sites, since the binding of the membrane permeable A(1) receptor ligand [3H]DPCPX to intact hippocampal nerve terminals (B(max)=1901+/-192 fM/mg protein) was markedly reduced (B(max)=321+/-30 fM/mg protein) by the membrane impermeable adenosine receptor antagonist, 8-sulfophenyltheophilline (25 microM). Further subcellular fractionation of hippocampal nerve terminals revealed that A(1) receptor immunoreactivity was strategically located in the active zone of presynaptic nerve terminals, as expected to understand the efficiency of A(1) receptors to depress neurotransmitter release. A(1) Receptors were also present in nerve terminals outside the active zone in accordance with the existence of a presynaptic A(1) receptor reserve. Finally, A(1) receptor immunoreactivity was evident in the postsynaptic density together with NMDA receptor subunits 1, 2A and 2B and with N-and P/Q-type calcium channel immunoreactivity, emphasizing the importance of A(1) receptors in the control of dendritic integration.     

Goldenhar's syndrome--case report

Goldenhar's syndrome is a rare condition described initially in the early 1950's. It is characterized by a combination of anomalies: dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, Gorlin suggested the name oculo-auriculo-vertebral (OAV) dysplasia for this condition and also included vertebral anomalies as signs of the syndrome. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. This work reports a case of Goldenhar's syndrome in an 11-year-old female, who presented all classical signs of this rare condition     

pH and calcium ion release of 2 root-end filling materials

OBJECTIVE: The purpose of this study was to evaluate the pH and calcium ion release of 2 materials used for root-end fillings and perforation repair. STUDY DESIGN: ProRoot and MTA-Angelus were placed in plastic tubes and immersed in glass flasks containing deionized water. After 3, 24, 72, and 168 hours, the water in which each had been immersed was tested to determine the pH changes and released calcium. RESULTS: The values for pH and calcium ion release were slightly higher for MTA-Angelus than ProRoot. The calcium release and pH of both materials were initially higher. CONCLUSION: The results suggest that both materials release calcium and promote alkaline pH.