Biomedical subjects

M Lolli

Publications and source records attributed to M Lolli.

5 recordsLinked to original sources

PubMed1997

Studies on agents with mixed NO-dependent vasodilating and beta-blocking activities.

PURPOSE: A series of derivatives having a propranolol-like moiety linked to NO-donor furoxan substructures were synthesized. The main objective of this investigation was to obtain agents with mixed NO-dependent vasodilating and beta-blocking activities. METHODS: Most of the target compounds were synthesized from the appropriate furoxans bearing XCH2CH2NH2 (X = O, S, SO2) chains at the 4 position of the ring, using Al(C2H5)3 in methylene chloride solution and (+/-)2,3-epoxypropyl 1-naphtyl ether. Two of the final products (X = CONH) were obtained by coupling the appropriate furoxancarboxylic acids with N-[2-hydroxy-3-(1-naphthoxy)propyl]-ethylenediamine. beta 1- and beta 2-blocking activities were examined on isolated guinea pig right atria and on guinea pig trachea respectively. Vasodilating properties were assessed on endothelium denuded strips of rat aorta. RESULTS: Some derivatives behave as well balanced "hybrids" displaying NO-dependent vasodilating and beta-blocking properties in the same concentration range. Some others display either prevalent beta-blocking or vasodilating activity. Generally speaking hybrid formation lowers the affinity for beta-receptors, in particular for beta 2-type, to give an increase in beta 1/beta 2 selectivity. CONCLUSIONS: The furoxan system is a flexible tool in designing analogues of propranolol whose NO-donating and beta-blocking properties are modulated over a wide range.

Adrenergic beta-Antagonists↗

PubMed1994

Detection of O6-butyl- and O6-(4-hydroxybutyl)guanine in urothelial and hepatic DNA of rats given the bladder carcinogen N-nitrosobutyl(4-hydroxybutyl)amine.

N-Nitrosobutyl(4-hydroxybutyl)amine (BBN) is a selective bladder carcinogen in rats. Its organ specificity may depend on several factors, including metabolic activation, DNA alkylation and repair within the target organ. Metabolic activation of BBN, which is asymmetrical, may result in butylating and 4-hydroxybutylating species. To test this view, BBN was administered as a single oral dose of 20 or 120 mg/rat or six doses of 20 mg/rat over 2 weeks. The animals given the single 120 mg dose were killed 3, 6 and 24 h after treatment. Rats given 20 mg or 6 x 20 mg BBN were killed 24 h after the last dose. DNA from liver and urothelial cells was hydrolyzed and analyzed for O6-butylguanine (O6-BuG) and O6-(4-hydroxybutyl)guanine [O6-(4-OH-Bu)G] as their pentafluorobenzyl-trimethylsilyl derivatives by high-resolution gas chromatography--negative ion chemical ionization mass spectrometry with selective ion recording after immunoaffinity extraction. Polyclonal antibodies raised against O6-(4-hydroxybutyl)-guanosine [O6-(4-OH-Bu)GR] were coupled to CNBr-activated Sepharose 4B. This was mixed with a gel coupled to antibodies raised against O6-BuG, already available in the laboratory, and the mixed gel was used for the one-step sample clean-up, enrichment and extraction of O6-(4-OH-Bu)G and O6-BuG from hydrolyzed DNA. O6-BuG in urothelial DNA of rats given a single dose of 120 mg BBN increased from 0.44 +/- 0.12 mumol/mol guanine (mean +/- SE) 3 h after treatment, to 17.9 +/- 7.23 mumol/mol guanine at 24 h. O6-(4-OH-Bu)G in the same tissue was 7.7 +/- 3.19 mumol/mol guanine 3 h after treatment and 12.2 +/- 7.01 mumol/mol guanine at 24 h. O6-BuG and O6-(4-OH-Bu)G were always lower in the liver than in urothelial cells. Twenty-four hours after a single dose of 20 mg BBN, urothelial O6-BuG was 5.41 +/- 1.73 mumol/mol guanine and did not accumulate after six doses of 20 mg/rat BBN, since it was 2.59 +/- 1.23 mumol/mol guanine 24 h after the last dose. O6-BuG in liver DNA was detectable after the single dose of 20 mg, but not after 6 x 20 mg/rat BBN. O6-(4-OH-Bu)G was not detected in either the bladder or the liver after 20 mg or after the six doses of BBN.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyclovir↗

PubMed1992

Urinary excretion of O6-butylguanine after the administration of N-nitroso-N-butylurea in rats.

O6-Butylguanine was detected in the urine of rats given the butylating agent N-nitroso-N-butylurea. O6-Butylguanine contents in the 24-h rat urine samples after i.p. doses of 50, 100, and 200 mg/kg N-nitroso-N-butylurea were 1.03 +/- 0.41 (SE), 8.30 +/- 1.70, and 59.53 +/- 6.52 pmol, respectively. This suggests that O6-butylguanine formation in nucleic acids might be repaired in vivo, possibly by base excision, besides other mechanisms. After i.v. doses of 0.1 and 1 mg/kg of O6-butylguanine to rats urinary excretion did not exceed 2% of the administered dose, suggesting that the amount of O6-butylguanine effectively released by base excision might be much larger than that detected in the urine after N-nitroso-N-butylurea. Inhibition of the enzyme O6-alkyl-DNA transferase by N-nitrosodimethylamine increased urinary O6-butylguanine resulting from exposure to N-nitroso-N-butylurea (100 mg/kg i.p.) up to four times, thus confirming an alternative DNA repair mechanism.

Animals↗

PubMed1991

[Understanding lateral and vertical gutta-percha condensation technique].

After a brief analysis of the materials and of the various techniques for filling root canals, the authors present the results obtained by a group of 5th year dental students of the Corso di Laurea in Odontoiatria e Protesi Dentaria from their first experiences at filling root canals. The techniques they used, lateral and vertical condensation of gutta-percha, were chosen for their widespread use and for the greater guarantee they offer. The results, which confirmed the expectations, show how lateral condensation is easier to perform by dentists with little experience. The vertical condensation technique, judging from our results, should be used only after a dentist has acquired experience and skill, because in the cases we observed there was a consistent unsatisfactory apical closure.

Gutta-Percha↗

PubMedDate not supplied

SAR studies on H2 antagonists containing alkylamino substituted 1,2, 5-thiadiazole 1-oxide moieties.

A number of ranitidine analogues in which the diamino-1,2,5-thiadiazole 1-oxide substructure bearing alkyl chains of different length is present as the urea equivalent group, were synthesised and studied for their lipophilic and H2 antagonist properties. Derivatives which displayed a logP < or = 3 behaved as competitive antagonists of histamine at H2 receptors present on guinea pig right atrium. The remaining more lipophilic members of the series showed an insurmountable antagonism not completely reversible after prolonged washing. A binding study suggested that an increase in the length of alkyl chain gave rise to hydrophobic interactions with the receptor which were responsible for the apparent irreversible H2 antagonism shown by the higher homologues of the series.

Animals↗