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Biomedical subjects

S Manzardo

Publications and source records attributed to S Manzardo.

At least 19 recordsLinked to original sources
PubMed1994

Interactions of P 1507, a new antioxidant agent, with phagocyte functions.

Toxic oxygen free radicals are believed to play a role in the pathogenesis of a number of respiratory diseases. In particular, pulmonary emphysema may occur because of the oxidative impairment of alpha 1-proteinase inhibitor (alpha 1-PI). We report in vitro data on a new thiol agent, P 1507 [N-5-(thioxo-L-prolyl)-L-cysteine], obtained in a series of experiments designed in view of its therapeutic potential in these clinical conditions. We found that P 1507 at the concentration of 5 x 10(-6) M was able to almost fully abolish the PMA-triggered PMN-induced oxidative impairment of alpha 1-PI. Protection may be due to the radical scavenger ability of P 1507, that markedly reduced superoxide anion production from PMNs. We also found that P 1507 did not significantly impair other defence mechanisms of PMNs (i.e. phagocytosis, chemotaxis and bactericidal activity). The release of cytokines (TNF-alpha, IL-6 and IL-8) from monocytes was not altered in the presence of P 1507. We conclude that the compound P 1507 may be considered for treatment of clinical conditions characterized by overload of oxidants, on the basis of its ability in preventing the oxidative damage of alpha 1-PI and of a lack of unwanted inhibitory effects towards defence mechanisms of phagocytes.

Antioxidants↗
PubMed1994

Experimental immunological screening tests on pidotimod.

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new biological response modifier, was administered to immunodepressed (by prednisolone, cyclophosphamide or methotrexate) mice by oral and intraperitoneal route (respectively up to 400 and 200 mg/kg) during several days (up to 9 days). The stimulatory action of the drug on cell-mediated immunity is investigated by measuring the rosette formation by the murine splenic lymphocytes ex vivo, by T- and B-lymphocytes ex vivo proliferative response to mitogens, by dinitrochlorobenzene delayed hypersensitivity induced on the ear, by the graft-versus-host reaction with immunodepressed mice as donors. In all tests pidotimod reveals a potent action in restoring the depressed reactivity. The action of pidotimod on humoral immunity is showed in two tests where the antibody response is induced by a thymus dependent (sheep erythrocytes) or a thymus independent (lipopolysaccharide) antigen. Pidotimod was active in both tests. Macrophage functions, anion superoxide production and the non-stimulated ex vivo chemotaxis reveal that pidotimod significantly reduces the immunodepressant action of prednisolone; particularly in i.p. treated mice the chemotaxis is likely to be restored to the levels of the non-immunodepressed controls. The colloidal china ink blood clearance in vivo in immunodepressed mice, after pidotimod treatment, results similar to that found in the control mice.

Adjuvants, Immunologic↗
PubMed1994

Protective effects of pidotimod against experimental bacterial infections in mice.

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) protected mice against experimental bacterial infections in different experimental models. In all tests the drug's effect was measured as protection from death. The activity of pidotimod was evident and statistically significant after 5 administrations before the bacterial challenges. Pidotimod was active against many bacterial species infections, its active dosages ranging from 0.01 to 100 mg/kg i.p. x 5 times. Pidotimod showed against some bacterial infections a protection similar or better than those of bestatin, N-acetylmuramyl-L-Ala-D-isoGlu-OH and tuftsin. It showed high protection against bacterial infections in cyclophosphamide-immunodepressed mice. Finally, pidotimod showed an additive or synergic activity in combination with beta-lactam antibiotics (cefotaxime, ampicillin) against bacterial infections in mice.

Adjuvants, Immunologic↗
PubMed1994

General pharmacology of pidotimod and testing for drug interactions.

Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) is a new biological response modifier. General pharmacology and interactions with some drugs were tested. The drug, at doses of 200 mg/kg i.p. and 400 mg/kg p.o., did not affect the normal behaviour, did not modify the responses to stimulation of autonomic nervous system or central nervous system. Pidotimod did not display any cardiovascular or respiratory effect up to 125 mg/kg i.v. in 3 animal species. The drug did not show antimicrobial or antifungal activities nor interact with some of the most common therapeutics (antibiotics, tolbutamide, pentobarbital, antihypertensives, chlorothiazide, warfarin, non-steroidal antiinflammatory agents). On the basis of these results pidotimod shows a safe profile; moreover it does not interact with many therapeutic agents.

Animals↗
PubMed1994

Toxicological evaluation of pidotimod.

This paper reports the toxicological evaluation of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6). Its acute toxicity in mice, rats and dogs was very low after oral, i.v., i.m. and i.p. administration. The repeated administration studies in rats were performed for 4 months via the i.p. route and for 12 months via the oral route. Pidotimod did not show toxic effects at dosages up to 200 mg/kg i.p. and 800 mg/kg p.o. These dosages correspond to 32.5 times the maximum dosage intended for clinical use. The repeated administration studies in dogs were performed for 26 weeks via the i.m. route and for 52 weeks via the oral route. Pidotimod did not show toxic effects at dosages up to 300 mg/kg i.m. and 600 mg/kg p.o.. It did not affect male or female rat fertility at dosages up to 600 mg/kg by oral and 500 mg/kg by i.v. route. The compound was not teratogenic in rats (600 mg/kg p.o. and 1000 mg/kg i.v.), with no effects on subsequent embryofoetal development at dosages up to 1000 mg/kg/day, and in rabbits (300 mg/kg p.o. and 500 mg/kg. i.v.). There were no peri- and postnatal toxic effects in rats (600 mg/kg p.o. and 500 mg/kg i.v.). Local tolerability of pidotimod after i.m. administration was very good. In conclusion pidotimod is characterized by a high safety margin in all animal species.

Animals↗
PubMed1993

Local tolerance of a new ciclopirox olamine vaginal preparation in rats and rabbits.

A new ciclopirox olamine vaginal preparation was tested for toxicity after topical vaginal administration for 28 days to rats and rabbits. At the end of the experiments animals were sacrificed for autopsy, the main organs were weighed, hematological, coagulative and biochemical parameters were checked and histological examinations were performed on uterus and vagina. The results demonstrated the good topical and systemic tolerance of this new vaginal formulation in rats and rabbits.

Administration, Intravaginal↗
PubMed1993

Pharmacokinetics of ciclopirox olamine after vaginal application to rabbits and patients.

The authors reported the plasma levels and pharmacokinetic parameters of ciclopirox olamine in rabbits after i.v. and intravaginal administrations and in female patients after vaginal administration. Plasma levels of total and free ciclopirox were determined by a HPLC method. In rabbit ciclopirox showed a half-life of 2.22 h and an intravaginal bioavailability of about 2%. In female patients ciclopirox showed low intravaginal absorption; this value might explain the good local and systemic tolerability and also the penetration of drug in deep tissue.

Administration, Intravaginal↗
PubMed1992

Activity and tolerability of tetridamine vaginal lavage in rats and women.

Tetridamine (2-methyl-3-methylamino-4,5,6,7-tetrahydroindazole) is a well known analgesic and anti-inflammatory drug. Here the activity and the tolerability of a new 0.134% tetridamine formulation in rats and women, are reported. Anti-inflammatory and analgesic tests were performed in Sprague-Dawley rats with carrageenin oedema; topical application of 0.134% tetridamine solution showed a marked reduction of paw swelling (-54.4%) and pain sensibility (-81.0%). A 28 days vaginal tolerability study performed on Sprague-Dawley rats with tetridamine lavage (0.2 ml/rat/day) showed, in comparison with control group, no changes in haematology, coagulation, clinical biochemistry and in histological examinations of uterus and vagina. Clinical studies (4 open and 1 double-blind) were performed on 93 women suffering from vulvovaginitis and cervicitis by treatment of 0.134% tetridamine vaginal lavage, two times daily, for 7 days. Tetridamine lavage reduced or eliminated all inflammation symptoms like burning, leucorrhea, etc. and resulted very well tolerated. From these pharmacotoxicological and clinical results we can conclude that tetridamine vaginal lavage is a new formulation with high activity and good tolerability.

Adult↗
PubMed1991

[Protective action of some compounds against the toxicity of acetaldehyde, acrolein and formaldehyde in the rat].

The Authors report the protective activity of some compounds against the toxicity of acetaldehyde, acrolein and formaldehyde in the rat. The compounds were orally administered 30 min before and 5 hours after the toxicant aldehyde administration (acetaldehyde 2150 mg/kg os; acrolein 75 mg/kg os; formaldehyde 950 mg/kg os). L-cysteine and L-ascorbic acid showed a good protective activity against the three toxicant aldehydes. Cysteamine, BHT and propyl gallate showed activity against acetaldehyde and formaldehyde. Quercetin was active only against acetaldehyde whereas alpha-tocopherol was inactive.

Acetaldehyde↗
PubMed1990

[Synthesis of gallic acid derivatives with L-thiazolidin-4-carboxylic acid and study on their antiradical and antitoxic activity].

The authors report the synthesis of three new derivatives of gallic acid with L-thiazolidine-4-carboxylic acid. The new compounds were tested for radical scavenger activity against doxorubicin toxicity in mice and for antitoxic activity against acetaldehyde and formaldehyde toxicities in rats. Unlike the utilized standards, the new compounds show no activity.

Acetaldehyde↗
PubMed1987

[Trans-1-(4-phenylcyclohexyl)ethylamine derivatives with antidepressant activity. II].

Some derivatives of trans-1-(4-phenylcyclohexyl)ethylamine (A) with a substituent at position 4 of the phenyl group were prepared and tested for antireserpine activity on the CNS. All compounds showed reduced activity compared with that of (A) except the amino derivative (II) which proved more active but at the same time showed increased toxicity and other adverse effects on the CNS.

5-Hydroxytryptophan↗
PubMed1985

Pharmacological study of a new hypolipidemic drug of prolonged activity, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid.

The hypolipidemic activity of the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) was assessed in various experimental conditions versus the corresponding activities of nicotinyl alcohol (NA), nicotinyl alcohol hemisuccinate (NAH), nicotinic acid (NAC), and pantethine tetranicotinate (PTN). In the normolipidemic rat, MG 28362 causes a more durable reduction of non-esterified fatty acids (NEFA) and serum triglycerides than the reference products. NEFA values return slowly to pretreatment levels without causing the rebound effect typical of most nicotinic acid derivatives. Likewise in the test of ethanol-induced hypertriglyceridemia, MG 28362 shows more pronounced and sustained activity compared to the reference products. It is also more effective on Triton hyperlipidemia and on diet-induced hypercholesterolemia; in the latter test, MG 28362 caused no triglyceride accumulation in the liver. Even at high dosage levels, MG 28362 did not cause the characteristic flushing of nicotinic acid congeners. Last, the new substance displays a fairly marked antiaggregating activity on blood platelets, some anti-hypoxic activity, and a generally low order of toxicity.

Animals↗
PubMed1985

Pantetheine and pantethine esters with hypolipidemic nicotinic acid derivatives.

We prepared several esters of pantetheine and pantethine, respectively, with 3-pyridineacetic acid and with 3-(3-pyridinemethoxycarbonyl)propionic acid, and we tested these products for their capacity to lower serum non-esterified fatty acids and triglycerides in normal animals. Among the products thus tested, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) displayed marked hypolipidemic activity, the action being of uncommonly long duration.

Animals↗
PubMed1982

[Derivatives of 4-phenylcyclohexylethylamine with antidepressive activity].

Several new derivatives of trans-1-(4-phenylcyclohexyl)-ethylamine (M.G. 6669) have been synthesized with various substituents at the alpha-carbon and/or at the amine nitrogen atom. All compounds were evaluated for a potential antidepressant activity taking M.G. 6669 as reference. They turned out to be less active than the reference substance. Pharmacological evaluation of M.G. 6669 itself was broadened during this work. The good antidepressant properties of this compound were confirmed, accompanied however by some toxic phenomena.

Aggression↗