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Biomedical subjects

A Pinelli

Publications and source records attributed to A Pinelli.

At least 37 records · Page 2Linked to original sources
PubMed1987

Comparison of two methods to evaluate drug-cytotoxicity on tumor cell lines cultured in vitro.

Some porphyrin compounds: P-NO2 and CVRIV were screened for cytotoxic activity against HT-29, LOVO, human tumor cell lines. The new radiometric assay was used for all cell lines. The soft agar cloning system was also utilized. The tested compounds decrease the growth index, measured in the radiometric assay, as 14CO2 production, and similarly depress the growth of tumor colonies on soft agar in the clonogenic assay. The cytotoxic effects of the compounds tested by these different methods were analysed statistically and resulted quantitatively similar. Based on these findings the radiometric assay represents a method, simple and rapid, which can be used as the clonogenic assay to screen new anticancer drugs.

Carbon Radioisotopes↗
PubMed1987

Cytotoxic effects and physicochemical properties of marycin: a new hematoporphyrin derivative.

This paper reports some physico-chemical properties and cytotoxic activity of marycin, a new hematoporphyrin derivative. The data show that marycin is a new compound, different from the other porphyrins tested. This product appears to be pure by adsorption or reversed phase thin-layer chromatography and high performance liquid chromatography and has chromatographic behavior different from those of other porphyrins tested. It does not appear to link to some tested metals and has a UV-visible absorbance spectrum different from that of a hematoporphyrin methylester. Furthermore, marycin has cytotoxic activity against K-562, ZR-75, MCF-7, HT-29, LOVO, human tumor cell lines and the MRC-9 human lung embryonic cell line. The new radiometric assay was used for all cell lines. Marycin decreases the growth index, measured by the radiometric assay as 14CO2 production. The cytotoxic activity is dose-dependent. Marycin is active at low doses but the activity varies with the cell line studied. The compound has low toxicity on the normal cell line MRC-9. Marycin is very liposoluble and would be expected to have high affinity and toxicity for tumors. The compound is active without light activation. How marcyin acts is still a matter for speculation.

Antineoplastic Agents↗
PubMed1985

Kynurenine may directly interact with GABA receptors in rat brain.

Previous studies have shown that kynurenine may have convulsant activity. In the present investigation the intracerebroventricular injection of L- but not D-kynurenine induced convulsions in the rat. In vitro, L- but not D-kynurenine was able to displace 3H-GABA from rat brain membrane preparations. The action was specific for 3H-GABA and was not observed with other ligands. The data suggest that the convulsant activity of L-kynurenine might be due to an interaction with GABA receptors.

Animals↗
PubMed1984

Experimental convulsions in rats induced by intraventricular administration of kynurenine and structurally related compounds.

Administration of L-kynurenine and some analogous molecules into the right lateral ventricle caused convulsive attacks in rats. These convulsions are tonic-clonic. Various modifications of the structure of L-kynurenine affected the production of convulsions. In particular, methylation of the carboxyl group increased the potency. Methylation of the carboxyl function and hydroxylation of the benzene ring greatly increased the latency and the duration of the convulsions. Removal of the carboxyl function or its reduction resulted in the loss of the epileptogenic effect. Masking of the amino function with formyl or acetyl residues also produced inactive compounds. The results of structural modification of the kynurenine carbon skeleton clearly show that the structure essential for stimulation of convulsive activity includes a free amino group and a free or masked carboxyl function. The molecular structure able to induce convulsive effects appears to be the laevo -isomer of kynurenine, since the dextro-form has been proved to be inactive. The convulsant activity, evaluated as the ED50, for L-kynurenine, is between that of bicuculline and pentamethylenetetrazole . The convulsant mechanism of kynurenine is unknown, but might very possibly involve interference with the activity of certain inhibitory neurotransmitters.

Animals↗
PubMed1984

Inhibitory effects of 2-guanidinebenzimidazole and 1-phenylbiguanide on gastric acid secretion in rats.

In this study 2-guanidinebenzimidazole (GBI) and 1-phenylbiguanide (PBG) appear to be capable of decreasing gastric acid secretion, while the compounds dimethylbiguanide and cyanoguanidine do not. Thus, the antisecretory effect is present when the biguanide groups are associated with lipophilic molecules. GBI and PBG depress gastric acid secretion, even when it has been stimulated by carbamoylcholine (carbachol) or betazole. The antihistamine effects of GBI and PBG on betazole-stimulated gastric acid secretion were confirmed by the inhibitory activity of these compounds on the isolated guinea pig auricle stimulated by histamine. The antimuscarine activity of GBI and PBG on carbachol-stimulated gastric acid secretion in rats is also supported by the way in which these same drugs depress the motility of the duodenum and colon of the anaesthetized cat stimulated by prostigmine. The above mentioned effects of these compounds are also associated with myolytic activity, since they decrease the spontaneous and histamine-stimulated motility of the duodenum and colon. GBI and PBG probably depress gastric acid secretion by interfering with both histamine and acetylcholine receptors and with other sites involved in the secretory process.

Animals↗
PubMed1982

Effect of in vivo increase of free fatty acids on human plasma protein binding of furosemide.

The in vivo effects of increased free fatty acid (FFA) plasma levels on the protein binding of furosemide were investigated in 30 adult-onset diabetics and 22 patients suffering from bacterial infections (gram- negative bacilli and gram-positive cocci). In diabetics, FFA were 2.43 +/- 1.63 mEq/l, and in subjects with bacterial infections 1.82 +/- 0.92 mEq/l. Furthermore, the percent of oleic acid and, to a very lesser extent, palmitoleic acid increased linearly with the increase of the FFA plasma level. The free furosemide fraction was about 1% or less in subjects with a molar ratio of FFA to albumin below 4, but a displacement of the drug from the plasma proteins occurred consistently when this ratio was above 4. At a molar ratio of FFA to albumin as high as 9.34, the free furosemide was 6.7% of the total concentration (8.9 microgram/ml). These results do not quantitatively agree with previous in vitro studies employing single fatty acids and human serum albumin, suggesting that in vivo plasma composition is not adequately reproduced during in vitro experiments on protein-binding displacement of drugs by FFA.

Adult↗
PubMed1981

Determination of the dissociation constant of carbonic anhydrase inhibitors: a computerized kinetic method based on esterase activity assay.

We evaluate a reliable procedure for in vitro determination of the dissociation constant, Ki, of carbonic anhydrase inhibitors. This pharmacologically important parameter is estimated, using a mathematical model derived from the Ackermann-Potter equation, by a computer-assisted nonlinear regression analysis of kinetic data from the enzyme-catalyzed hydrolysis of p-nitrophenyl acetate. The proposed method has the additional advantage, over the ones that require the use of only paper and pencil, of giving standard errors for the estimated parameters. Based on our findings, a comparison of the reported values for the inhibition of carbonic anhydrase by twelve sulfamoyl drugs is presented, and the difficulties associated with the determination of dissociation constants for carbonic anhydrase inhibitors are discussed.

Carbonic Anhydrase Inhibitors↗
PubMed1981

Drugs affecting porphyrin and lipid metabolism in rats: effects exerted by allylisopropylacetamide and related molecules.

Allylisopropylacetamide (AIA), a drug known to cause lesions in porphyrin and lipid metabolism, and drugs with structure related to AIA [propylisopropylacetamide (PIA) and 2-isopropyl-4-hydroxyvaleric acid] were injected subcutaneously into rats. Measurements were taken of the effect of these compounds on the levels of 5-aminolevulinic acid synthetase (ALA synthetase) and hepatic porphyrins and on the values of hepatic and plasmatic triglycerides and plasma free fatty acids. To a different degree, both AIA and PIA increase the activity of ALA synthetase, and also increase the levels of hepatic porphyrins and hepatic and plasmatic triglycerides, while they both initially lower the levels of plasmatic free fatty acids (FFAs). The administration of 2-isopropyl-4-hydroxyvaleric acid has no effect on the parameters studied. The findings seem to suggest that the activity affecting porphyrin and lipid metabolism is connected in both cases with the presence of the amide function.

5-Aminolevulinate Synthetase↗
PubMed1981

Liquid-phase synthesis of naturally occurring peptides, I. Syntheses of leucine-enkephalin and methionine-enkephalin of a p-alkoxybenzyl-modified soluble support.

The liquid-phase synthesis of two pentapeptides corresponding to the amino acid sequence of Leu- and Met-enkephalin is described. Modified monofunctional poly(ethylene glycol) containing a p-alkoxybenzyl alcohol functional group was employed as the soluble polymeric support. Cleavage of the peptides from the polymer, as well as the removal of protecting groups, was achieved with trifluoroacetic acid at room temperature. The free peptides were purified by column chromatography on DEAE-Sephadex, and were identical in both physical and biological characteristics with reference material. The results showed that the proposed support is effective for a mild cleavage of peptides from the soluble polymer during liquid-phase synthesis.

Amino Acids↗