Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration?

The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (HO). In this regard, while it is well known that 4-methylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of HO, a mechanism that may indirectly affect catalase whose enzymatic activity requires HO. The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism.

After decades of uncertainties and drawbacks, the study on the role and significance of acetaldehyde in the effects of ethanol seemed to have found its main paths. Accordingly, the effects of acetaldehyde, after its systemic or central administration and as obtained following ethanol metabolism, looked as they were extensively characterized. However, almost 5 years after this research appeared at its highest momentum, the investigations on this topic have been revitalized on at least three main directions: (1) the role and the behavioral significance of acetaldehyde in different phases of ethanol self-administration and in voluntary ethanol consumption; (2) the distinction, in the central effects of ethanol, between those arising from its non-metabolized fraction and those attributable to ethanol-derived acetaldehyde; and (3) the role of the acetaldehyde-dopamine condensation product, salsolinol.

Role of ethanol-derived acetaldehyde in operant oral self-administration of ethanol in rats.

Rationale: The role of ethanol-derived acetaldehyde has not been examined yet on performance in a model of operant oral self-administration. However, previous studies reported that an acetaldehyde-sequestering agent, D-penicillamine (DP) and an inhibitor of catalase-mediated acetaldehyde production, 3-amino-1,2,4-triazole (3-AT) reduce voluntary ethanol consumption.

Objectives: The aim of our investigation was to evaluate the effects of DP and 3-AT on acquisition and maintenance of oral operant ethanol self-administration.

Change of cystine/glutamate antiporter expression in ethanol-dependent rats.

Background: Some drugs of abuse down regulate the expression of cystine/glutamate (xCT) antiporter in the nucleus accumbens (Acb) after extinction or withdrawal. The altered level of xCT exchanger in Acb, a structure involved in ethanol reinforcement, may contribute to the pathological glutamatergic signaling, linked to addiction. We hypothesized that the expression of xCT may be changed in Acb and whole brain also in non-dependent (occasional drinkers), ethanol-dependent rats, as well as, during ethanol withdrawal.

Neonatal taurine administration modifies metabolic programming in male mice.

The semi-essential amino-acid taurine is involved in glucose homeostasis either in adults or in parental life. Taurine is currently used in neonatal life because it is added to milk formula for babies, and to parental solution for prematures. Here, it has been examined whether taurine administration in lactation modifies adult glucose metabolism.

Temperature dependence of chaperone-like activity and oligomeric state of alphaB-crystallin.

The chaperone-like activity and the oligomeric state of alphaB-crystallin were studied at different temperatures and in the presence of urea and thiocyanate. The activity, assessed measuring the ability of alphaB-crystallin to prevent the aggregation of denatured insulin, strongly depends on temperature. While a significant activity increase was detected at 42 degrees C, the presence of urea and thiocyanate does not affect the protein activity in an irreversible way.

Effect of simulated microgravity on PGE2-induced edema and hyperalgesia in rat paws: pharmacological data and biochemical correlates.

The aim of the present study has been to investigate the effect of conditions of modeled microgravity using a three-dimensional clinostat (Random Positioning Machine, RPM) on edema and thermal hyperalgesia induced by prostaglandin E2 (PGE2) in the hind paw of rat. Our results showed that RPM reduced PGE2-evoked edema associated to a significant decrease in hyperalgesia compared to ground control animals. To further characterize the mechanisms by which RPM induces anti-inflammatory and anti-hyperalgesic action, we performed biochemical assays of PGE2 and Western immunoblot experiments to assess whether the intraplantar administration of exogenous PGE2 modifies the expression of the iNOS.

Is taurine beneficial in reducing risk factors for diabetes mellitus?

Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in the retina, lens, and peripheral nerve, although its effects on diabetic kidney are dubious. Interestingly, long-term taurine supplementation reduces the mortality rate in diabetic rats.

Effect of low doses of ethanol on platelet function in long-life abstainers and moderate-wine drinkers.

In vitro, high concentrations of ethanol (EtOH) reduce platelet aggregation. Less is known about the effect of low EtOH doses on platelet function in a selected human population of long-life abstainers and low moderate-wine drinkers to avoid rebound effect of EtOH on platelet aggregation. Results of our experiments suggest that moderate-wine drinkers have higher levels of high density lipoprotein (HDL) than long-life abstainers while fibrinogen levels are unchanged.

Inhibition of the MEK/ERK signaling pathway by the novel antimetastatic agent NAMI-A down regulates c-myc gene expression and endothelial cell proliferation.

Imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate (NAMI-A) is a novel ruthenium-containing experimental antimetastatic agent. Compelling evidence ascribes a pivotal role to endothelial cells in the orchestration of tumor angiogenesis and metastatic growth, suggesting antiangiogenic therapy as an attractive approach for anticancer treatment. In this context, activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway has been found fundamental in transducing extracellular stimuli that modulate a number of cellular process including cell proliferation, migration and invasion.

The anti-metastatic agent imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate induces endothelial cell apoptosis by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway.

Imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate (NAMI-A) is a new ruthenium compound active against lung metastasis in vivo and tumor cell invasion in vitro. Since angiogenesis was recognized as a key event in the metastasizing process, the manipulation of neo-vessel formation has been developed as a new therapeutic approach. Within this context, a pivotal role for apoptosis in regulating cellular growth has been proposed.

Platelet antioxidant enzymes in insulin-dependent diabetes mellitus.

Background: The measurement of the peroxidase scavenging system represented by the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in blood cells of diabetic patients has, in the past, given equivocal results. Likewise, the role of these intracellular enzymatic scavengers against the oxidative stress of diabetes-associated microangiopathic complications is unknown.

Methods: Choosing platelets as cell model (as commonly done in previous studies), the aim of this study was to relate the platelet content of SOD, catalase and GSH-Px to the presence of diabetes, as well as to the presence of nephropathy and retinopathy in 35 insulin-dependent diabetic patients, as compared to 10 age-matched control subjects.

Dissociation of human alphaB-crystallin aggregates by thiocyanate is structurally and functionally reversible.

Conformational modifications and changes in the aggregation state of human alphaB-crystallin were investigated at different concentrations of SDS, KBr, urea, and NH4SCN and at different temperatures. Intrinsic fluorescence measurements indicated complete and reversible unfolding of the protein at 2 M NH4SCN, whereas the concentration of urea required for complete and irreversible unfolding was 6 M. Gel permeation chromatography indicated almost complete dissociation of the micelle-like aggregate of alphaB-crystallin in 2 M NH4SCN, but only partial dissociation into large-sized aggregates in 6 M urea.

Heparin inhibits phorbol ester-induced ornithine decarboxylase gene expression in endothelial cells.

Glycosaminoglycans regulate angiogenesis by affecting the availability of different growth factors for the endothelial cell (EC). However, little is known about the molecular and functional consequences resulting from direct interaction of these polyelectrolytes with the EC. Here we show that heparin markedly inhibited serum-stimulated DNA synthesis and ornithine decarboxylase (ODC) mRNA expression in human endothelial cells (HEC).

Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells.

Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro. However, the role played by cytolitic molecules that may participate in Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of this work was to study whether soluble molecules released by A.

Raised erythrocyte polyamine levels in non-insulin-dependent diabetes mellitus with great vessel disease and albuminuria.

Erythrocyte content of polyamines has been previously found increased in insulin-dependent diabetes mellitus with microalbuminuria. Since increased urinary albumin excretion (AER) is associated with the presence of vascular diseases in non-insulin-dependent diabetes mellitus (NIDDM) the aim of this study was to verify the hypothesis that the presence of increased urinary albumin excretion (AER), and of macroangiopathy in NIDDM would be related to a significant modification in polyamine erythrocyte levels. The erythrocyte content of spermine and spermidine was measured by a HPLC method in 39 patients affected with NIDDM and in 24 age- and sex-matched healthy control subjects, evaluating the relationship between erythrocyte polyamines of NIDDM patients with the presence of macroangiopathy as well as with retinopathy or increased AER (> or = 20 micrograms/ml).

Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster. I. Regulation of prodynorphin gene expression by nuclear protein kinase C.

Prodynorphin gene expression was investigated in adult ventricular myocytes isolated from normal (F1B) or cardiomyopathic (BIO 14.6) hamsters. Prodynorphin mRNA levels were higher in cardiomyopathic than in control myocytes and were stimulated by treatment of control cells with the protein kinase C (PKC) activator 1, 2-dioctanoyl-sn-glycerol.

NMDA receptors play an anti-aggregating role in human platelets.

Receptors for different monoamines, peptides and other neurohormones are present in the plasma membrane of platelets, and the sophisticated process of haemostasis is regulated by the interplay of their physiologic agonists (1). The recent report of a platelet binding site for phencyclidine (2) suggested a possible role of N-methyl-D-aspartate (NMDA) receptors in platelet function. Isotherms of [3H]-glutamate (GLU), [3H]-CGP-39653, [3H]-glycine (GLY) and [3H]-MK-801 carried out in platelet membranes yielded Bmax and Kd values for these ligands similar to those present in neurons, and NMDA only partially displaced [3H]-GLU.

Carbon centered radicals reduce the density of L-type calcium channels in rat cardiac membranes.

The carbon centered radicals generated by preincubation of cumene hydroperoxide with rat cardiac membranes dose dependently reduced the Bmax of [3H]nitrendipine binding, while KD was unchanged. The reduction induced by cumene hydroperoxide was prevented by 2,6-di-t-butlyl-4-methyl-phenol. The generation of OH did not influence the [3H]nitrendipine binding; also other oxidative agents (H2O2 and HClO4) did not modify this binding.

Phorbol ester regulation of opioid peptide gene expression in myocardial cells. Role of nuclear protein kinase.

Opioid peptide gene expression was characterized in adult rat ventricular cardiac myocytes that had been cultured in the absence or the presence of phorbol 12-myristate 13-acetate. The phorbol ester induced a concentration- and time-dependent increase of prodynorphin mRNA, the maximal effect being reached after 4 h of treatment. The increase in mRNA expression was suppressed by incubation of cardiomyocytes with staurosporine, a putative protein kinase C inhibitor, and was not observed when the cells were cultured in the presence of the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate.

Kinetic changes of alpha B crystallin expression in neoplastic cells and syngeneic rat fibroblasts at various subculture stages.

Alpha B crystallin, a structural at variable levels, in many extraocular tissues where it plays a protective role in stress conditions. In fact, heat or toxic shocks, as well as pathological states, increase alpha B crystallin levels in many cell types. Here we show that alpha B crystallin expression is also modulated in subcultures of rat fibroblasts and Galliera sarcoma cells.

Effects of taurine and hypotaurine on lipid peroxidation.

It has been suggested that hypotaurine might inhibit lipid peroxidation in vivo by scavenging the initiator OH. The results presented demonstrate that hypotaurine affects other reactions relevant to the initiation, propagation and termination phases of lipid peroxidation. Hypotaurine a) decreases Fe2+ autoxidation, either spontaneous or catalyzed by Fe3+, that may generate perferryl iron; b) decreases Fe2+ oxidation, by cumene hydroperoxide, that forms the alkoxy radical; c) inhibits the lipid hydroperoxide dependent lipid peroxidation, favoring the onset of the termination phase.

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied.

Alpha B crystallin is constitutively expressed in cultures of bovine articular chondrocytes.

alpha B crystallin is a small heat shock protein constitutively expressed in the mammalian lens and in a variety of extraocular tissues. We report here the presence of alpha B crystallin also in bovine articular chondrocytes by means of an immunoblot and immunofluorescence analysis carried out with anti-alpha B crystallin polyclonal antibodies. The expression level of alpha B crystallin can be further induced by a short heat shock treatment of chondrocytes as well as cell treatment with cadmium bromide or calcium ionophore A 23187.

Cytotoxicity of lazaroid U-75412E in human epithelial cell line (Wish).

The 21-aminosteroids (or lazaroids) are a recently synthesized class of compounds demonstrated to protect tissue against damage induced by trauma and/or ischemia. Currently, very little is known about the biological effects of lazaroids. In this work the action of lazaroid U-75412E on a human epithelial cell line (Wish) was evaluated.