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Biomedical subjects

A Bertelli

Publications and source records attributed to A Bertelli.

At least 109 records · Page 6Linked to original sources

Protective action of acetylcarnitine on NADPH-induced lipid peroxidation of cardiac microsomes.

Rat cardiac microsomes treated with NADPH generated a chemiluminescence, detected by the chemilumigenic probe lucigenin. The chemiluminescent signal, which is an index of lipid peroxidation, was found to be inhibited by acetylcarnitine in a dose-dependent way. Superoxide dismutase (SOD) and inhibitors of arachidonate metabolism were also effective in preventing light emission. The combined action of acetylcarnitine plus SOD and acetylcarnitine plus indomethacin suggested a possible common target for the compounds. When tested on superoxide production from isolated human neutrophils detected both by luminol-amplified chemiluminescence and cytochrome C reduction, acetylcarnitine did not show any inhibitory effect. The results of these experiments demonstrate the antioxidant properties of acetylcarnitine, even if they cannot clarify the specific target of the drug action.

Acetylcarnitine↗

Pharmacological evidence of morphine-induced inhibition of gastric mucus synthesis in rats.

The effects of morphine, administered at graded doses by either intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) routes, have been investigated on acid and pepsin outputs, secretory volume, ulcer score, free and bound gastric mucus, in pylorus-ligated rats. Morphine i.c.v. induced a dose-dependent inhibition of secretory volume, acid and pepsin outputs and ulcer score, without modification of either free or bound mucoproteins. Naloxone i.c.v. had no effect per se, but prevented the inhibitory effects of i.c.v. morphine. Morphine i.p. produced a dose-dependent inhibition of gastric secretory volume, acid and pepsin outputs, as well as both free and wall-bound mucoproteins. By contrast, the effect of i.p. morphine on ulcer score was not dose-dependent: the dose of 5 mg/kg induced significant exacerbation of gastric lesions. Naloxone at 0.8 mg/kg i.p. had no effect per se, whereas at the dose of 4 mg/kg it significantly increased bound gastric mucus. The dose of 0.8 mg/kg antagonized the effects of morphine on gastric secretory volume, acidity, pepsin and ulcer score, but not on gastric mucus. These results indicate that morphine affects gastric acidity through central and peripheral opiate receptors, whereas gastric mucus synthesis appears to be regulated through peripheral opioid pathways.

Animals↗

Comparative nephrotoxicity and tissue accumulation of dactimicin, amikacin and gentamicin.

Dactimicin (ST 900) is a new pseudo-disaccharide aminoglycoside antibiotic which has been shown to be active against systemic infections in mice. Few data have so far been reported on dactimicin tissue accumulation or its potential nephrotoxicity. In this study, nephrotoxicity and renal tissue concentrations of gentamicin, amikacin and dactimicin were compared in Wistar rats. Liver, heart and lung accumulation of these drugs were also evaluated. Groups of 5 rats were respectively injected with 100 mg/kg body weight of the different drugs daily for 7 days. Five control rats were also injected with saline. Twenty-four hours after the last injection, all rats were sacrificed and bled to death. Blood samples were taken for BUN and serum creatinine assay. Kidney, liver, heart and lung tissues, as well as blood, were removed and processed for microbiological assay of gentamicin, amikacin and dactimicin. The results of this study showed that dactimicin, as well as amikacin, did not induce any significant increase in BUN and serum creatinine, while gentamicin administration resulted in severe uraemia in all rats. Consequently a much higher accumulation of gentamicin than amikacin and dactimicin was achieved in serum and tissues.

Amikacin↗

Comparative effects of gentamicin, amikacin and dactimicin on excretion of N-acetyl-beta-D-glucosaminidase (NAG) and kidney histological pattern in rats.

Dactimicin (DC) is a new pseudodisaccharide aminoglycoside antibiotic containing a formimidoyl group in its molecule (1). DC exhibits a greater antibacterial activity than other aminoglycosides against the clinical isolates of Serratia marcescens and is active against many gentamicin- and amikacin-resistant bacteria. This characteristic of the drug appears to be linked with a probable protective action exerted by the formimidoyl group in its structure. The greatest limitation in the clinical use of aminoglycosides is their potential for nephrotoxicity. The present study compares the renal effects of DC versus gentamicin (GT) and amikacin (AK), respectively the most and the least nephrotoxic pseudotrisaccharide aminoglycosides in present use (2), evaluating the urinary NAG excretion and the histological changes induced in the kidney.

Acetylglucosaminidase↗

Studies in vitro on the effects of rhein on the chemotaxis of human leukocytes.

Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacetylrhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis. Its action mechanism in rheumatic pathology has not been fully explained. It is known that DAR, while not inhibiting the formation of prostaglandins, inhibits certain proteolytic enzymes, and acts on phlogistic cells by lysosomal enzymic and superoxide-anion modifications. Moreover DAR modifies phagocytic functions and the motility of cells. This paper is a contribution to the clarification of the last point, namely the effect of rhein on cell motility. It reports that in vitro no effect of R on random migration was found, but instead a double inhibiting effect on chemotaxis (i.e. a low-dosage and a high-dosage effect). Furthermore, R did not modify the inhibition or induce modification of chemotaxis by vinblastine. Finally R cancelled the stimulating effect of ionic potassium. The results thus indicate that R acts on the chemotaxis of the leukocytes with a complex action at different doses. The action mechanism is probably due to a membrane effect, since rhein (R) did not modify the chemotaxis-inhibiting activity of vinblastine but did interfere with the stimulating effect of K+.

Anthraquinones↗

Effects of white wine, Coke and water on basal and food-stimulated gastric acid secretion and gastrin release in the dog.

The effects of three types of white wine (10% ethanol; pH 2.84-3.26), Coke (pH 2.45) and water (pH 8.03) on basal and food-stimulated gastric acid secretion in dogs were investigated. Water and Coke did not significantly modify acid secretion and gastrin release under basal conditions. By contrast, white wine or water +10% ethanol significantly increased acid secretion, with a tendency to elevate plasma gastrin concentrations. Acid secretion and gastrin release induced by a standard meal were not significantly modified by previous administration of Coke and water. In contrast, white wine and water +10% ethanol significantly increased food-stimulated total acid output, without changing plasma gastrin levels. It is concluded that Coke and water have only trivial effects on basal and on food-stimulated gastric acid secretion and gastrin release in the dog. The gastric stimulant effect of white wine is mainly related to its percentage of alcohol regardless of the slight differences in pH of the solutions.

Animals↗

Tissue concentrations of coenzyme Q in liver of rats intoxicated by carbon tetrachloride.

The protective action of hepatic cells of the coenzyme CoQ10 was checked against the well-known hepatolesive agent carbon tetrachloride (CCl4). It was found that CoQ10 pretreatment strongly reduced the CCl4-induced lesions in rat liver. The most important of these lesions was a marked steatosis, together with focal necrosis, Kupffer-cell reaction and signs of phlogosis and fibroblastic proliferation. The protective effects of CoQ10 seemed to be dose-dependent. The variation of CoQ9 concentration in the liver was not significant at any of the doses used.

Animals↗

Enzymuria in aminoglycoside-induced kidney damage. Comparative study of gentamicin, amikacin, sisomicin and netilmicin.

Forty-one patients with urinary tract infections were randomly assigned to receive for six days gentamicin, amikacin, sisomicin or netilmicin. The dose for each patient was calculated according to creatinine clearance and lean body mass in order to avoid overdosages. Urinary enzymes (alpha-glucosidase, gamma-glutamyltranspeptidase and muramidase), serum creatinine and creatinine clearance, proteinuria and urinary sediment were evaluated for nephrotoxicity. None of the patients developed nephrotoxicity, but urinary enzymes rose significantly in all. The statistical analysis of enzymuria during the treatment permitted the definition of a rank order of the nephrotoxic potential of the aminoglycosides studied.

Adolescent↗

Experimental comparative renal toxicity of lithium and rubidium.

Rat kidney was perfused using Krebs solution containing 3 or 6 mEq/l lithium or 3 or 6 mEq/l rubidium; the histological lesions thus induced were compared. Rubidium-induced lesions, irrespective of concentrations, consisted of tubular dilations, degeneration and necrosis very similar to those induced by lower concentrations of lithium; moreover, Bowman space alterations were observed. In contrast, lithium-induced damage was dose-dependent: 6 mEq/l solution induced severe tubular damage with necrosis, endoluminal cellular debris and hyaline substance.

Animals↗

Studies on the effects of anthracyclines on mitochondrial respiration in vitro.

Aclacinomycin, 4'-epi-doxorubicin and 4'-epi-tetrahydropyranyl-adriamycin, three novel anthraquinone derivatives under investigation for their antitumour activity, showed an inhibitory effect on the in vitro respiration of mitochondria from rat hearts. The inhibition proved to be concentration-dependent in the range 0.05 to 1.40 mM and both the NADH-oxidase and the succinate oxidase systems were affected to different extents. Among the compounds tested, 4'-epi-tetrahydropyranyl-adriamycin appeared to be the least powerful effector, requiring a significantly higher concentration for 50% inhibition of oxidation than doxorubicin and the other analogues examined.

Aclarubicin↗

Inhibitory effects of several anthracyclines on mitochondrial respiration and coenzyme Q10 protection.

A set of three novel anthracyclines, active as antitumour agents, has been examined for their possible effects on rat heart mitochondrial respiration. The in vitro inhibiting effects of the compounds have been compared with that of the older doxorubicin. Aclacinomycin was generally more inhibitory than doxorubicin, 4'-epi-doxorubicin and 4'-epi-tetrahydropyranyl-adriamycin, with both succinate and NAD+-linked substrates. Attempts to prevent anthracycline from inhibiting the succinate oxidase activity by means of adding exogenous coenzyme Q10 gave encouraging results, the inhibiting effect being in fact reduced.

Aclarubicin↗

Current trends in the research on antiinflammatory agents.

Current trends of pharmacological research on inflammation are outlined, with particular reference to some agents differing from the aspirin-like and the corticosteroids in their mode and mechanism of action. As an example, animal models used for the study of benzydamine, and its predominant features, are illustrated. A discussion is also made on the role of protein denaturation in inflammatory conditions where cell degeneration prevails over the active response, and the rationale used for developing bendazac is presented.

Adrenal Cortex Hormones↗

Some aspects of the critical evaluation of peptic ulcer therapy in patients.

The disease peptic ulcer in patients does not present a uniform clinical entity. Hence, the therapeutic approaches to peptic ulcers are significantly different. Independently from the therapeutically given drugs, some common problems can be found in the methods of critical evaluation of the peptic ulcer therapy in patients. This paper deals with goals, the possible ways to evaluate critically the efficacy of peptic ulcer therapy and the problems in patients in relation to both evaluation of clinical pharmacology and as well as to everyday medical practice.

Anti-Ulcer Agents↗

Inhibiting effect of levamisole on superoxide production from rat mast cells.

The aim of the present study was to test whether levamisole acts as a superoxide scavenger. The drug was incubated at four different concentrations (range 1, 5, 10, 20 micrograms/ml) with purified rat mast cells which were then induced to generate superoxide ions, by challenge with compound 48/80 (1 microgram/ml). Ten minutes preincubation with the drug completely abolished superoxide ions production. Addition of levamisole to the cell suspension simultaneously with the releaser caused full inhibition of O2(-) generation at the lowest dose, while higher doses failed to suppress 48/80 induced O2(-) generation. In a cell-free superoxide-generating system, like xanthine-xanthine oxidase, levamisole did not act as a superoxide scavenger at any of the doses tested.

Animals↗

Immunomodulators and enzymes of purine metabolism in human lymphocytes.

The enzymes ADA and PNP were evaluated in lymphocytic subpopulations in peripheral blood obtained from healthy subjects, elderly subjects and patients with immunoproliferative diseases. Some similar assessments were performed on lymphoid cells from cord blood. Preliminary studies indicate that Thymostimulin can in some cases correct enzymic defects.

Adenosine Deaminase↗

Gastric cytoprotection by pirenzepine: role of endogenous catecholamines.

Acute gastric ulcerations were produced in fasted rats by pylorus ligation or by administration of polymyxin B or absolute ethanol. In pylorus-ligated rats pirenzepine 25 mg/kg per os decreased by about 50% the ulceration score, without affecting gastric acid and pepsin output. A similar percentage inhibition of ulceration score with no change of gastric acidity was obtained with pirenzepine 5 mg/kg per os in the case of gastric lesions provoked by polymyxin B. Ethanol-induced gastric lesions were also markedly reduced by pirenzepine, with 50% inhibition occurring with the dose of 25 mg/kg. The release of catecholamines from rat isolated gastric tissue during stimulation of sympathetic periarterial nerves was significantly reduced by pirenzepine 1 X 10(-6) g/ml. The present results indicate that pirenzepine significantly reduced gastric lesions induced by various stimulants; the protective effect of pirenzepine did not appear to be related to increased sympathetic tone.

Animals↗

Gastric cytoprotection by pirenzepine is not mediated by catecholamines.

The effects of pirenzepine (in a dose of 25.0 mg X kg-1) and atropine (2.5 mg X kg-1) were studied on the development of gastric ulceration produced by pylorus ligation, polymyxin B and absolute ethanol, as well as on the gastric secretory responses and plasma level of noradrenaline. It was found that: (1) pirenzepine significantly decreased the development of ulcer formation produced by pylorus ligation, polymyxin B and absolute ethanol without any antisecretory response; (2) atropine inhibited gastric acid secretion, but no effect was obtained on ulcus produced by pylorus ligation, polymyxin B and absolute ethanol; (3) the plasma level of noradrenaline could be decreased by atropine and pirenzepine, although the difference did not reach statistical significance. It has been concluded that catecholamines are not involved in the gastric cytoprotective mechanism of pirenzepine.

Animals↗