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Biomedical subjects

M Pinto

Publications and source records attributed to M Pinto.

At least 109 records · Page 6Linked to original sources
PubMed1981

Ellipticine, 9-hydroxyellipticine, and 9-hydroxyellipiticinum: some biochemical properties of possible pharmacologic significance.

Ellipticine, 5,11-dimethyl-(6H)-pyrido-(4,3,b)-carbazole (NSC 71795) is a potent cytotoxic and antitumor agent. Several of its derivatives share these properties and nine hydroxylated compounds are even more potent. 2-Methyl-9-hydorxyellipticinium (NSC 264-137) has thus recently been shown to display some therapeutic effectiveness in human breast cancers. The biochemical mechanism of this action is discussed in this paper. DNA has been implied as the target of ellipticine and some derivatives; however, these drugs do not break DNA in cultured L1210 cells. Moreover, several other biochemical constituents are able to bind these compounds in vitro as efficiently as DNA. In this paper the interactions between ellipticine and some of those derivatives and (a) ascitic phospholipids monolayers and (b) cytochrome P450 microsomal proteins are studied and discussed. Finally, the hypothesis that the nonhydroxylated ellipticine derivatives might be better cytotoxic agents because they can be oxidized and generate free radical species through a monovalent electron transfer process is presented. This hypothesis is supported by experiments carried out on the oxidation of 9-hydroxyellipticine and 2-methyl-9-hydroxyellipticine by peroxidases.

Alkaloids↗
PubMed1980

A reassessment of the karyotype of Papio ursinus. Homoeology between human chromosome 15 and 22 and a characteristic submetacentric baboon chromosome.

The Giemsa-banded karyotype of the chacma baboon, Papio ursinus, was shown to be identical to that of Papio hamadryas. Comparison of G-banded P. ursinus (PUR) chromosomes with those of man (HSA) showed close morphological homoeology between PUR and HSA chromosomes 5, 8, 12, 19, and X, and partial homology for seven and 22 and was the only Papio chromosome containing a nucleolar organizer region (NOR). This baboon chromosome, therefore, shows genetic homoeology with human acrocentrics for a least 18S and 28S rRNA gene loci. It is postulated that HSA 15 and 22 originated from the fission of a larger submetacentric chromosome in a lower primate.

Animals↗
PubMed1980

Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone.

To investigate the possibility that GH release induced by gamma-aminobutyric acid (GABA) in man is mediated by a dopaminergic mechanism(s), we evaluated the effect of two antidopaminergic compounds, pimozide and domperidone, on the plasma GH response to acute GABA administration (5 g, orally). Only the former compound can freely cross the blood-brain barrier. In 9 normal volunteers, GABA caused a significant increase of plasma GH levels (P < 0.0001 vs. GH levels in a group of 14 controls). In these subjects, pimozide (6 mg/day, orally, for 4 days) significantly blunted the GH elevation induced by GABA (P < 0.01). Unlike pimozide, in 8 additional subjects, domperidone (4 mg injected iv immediately before GABA administration) did not influence the GABA-induced GH response. GABA did not alter either baseline or pimozide-stimulated plasma PRL levels. Likewise, it did not significantly modify the brisk PRL rise after domperidone injection. These findings are consistent with the hypothesis that GABA-stimulated GH secretion is mediated via dopamine release at a suprapituitary level. With regard to PRL secretion, no GABA-dopamine interactions are readily apparent.

Adult↗
PubMed1980

Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man.

A single oral dose of 5 g gamma aminobutyric acid (GABA) was given to 19 subjects and serial venous blood samples were obtained before and 3 h after drug administration. A placebo was administered to 18 subjects who served as controls. GABA caused a significant elevation of plasma growth hormone levels (P less than 0.001), but did not consistently alter plasma prolactin concentration since only 5 out of 15 subjects showed an increase of the hormone. Eight additional subjects were submitted to an insulin tolerance test before and after per os administration of 18 g GABA daily for 4 days. Protracted GABA treatment significantly blunted the response of growth hormone and enhanced that of prolactin to insulin hypoglycaemia (P less than 0.01). These results indicate that pharmacological doses of GABA affect growth hormone and prolactin secretion in man. The precise nature of GABA's effects as well as its mechanism of action remains to be clarified.

Administration, Oral↗
PubMed1978

Plaque-forming cells in mice after experimental infection with Brucella abortus.

Cells producing antibody to brucella lipopolysaccharide were detected in spleens of mice infected with Brucella abortus 19 by a hemolytic plaque assay. The appearance of immunoglobulin M-producing cells preceded humoral antibodies. The primary plaques were observed 5 days after inoculation, and they were still present by day 70.

Animals↗
PubMed1978

Foamy myocardial transformation of infancy: 'lipid' or 'histiocytoid' myocardiopathy.

Two cases of a distinctive infantile myocardiopathy were studied by light and electron microscopy. They represent the 15th and 16th reported examples of this condition, and include the first associated with morphologically classical endocardial fibroelastosis. The condition is characterized by the presence of clusters of foamy or granular cells scattered throughout the myocardium. Ultrastructural studies indicate (1) that lipid storage is not a feature of the condition, and (2) that the abnormal fibers are characterized by a reduced number of fibrils and an increased number of mitochondria. It is proposed that the lesion should be called "foamy myocardial transformation of infancy," and it is speculated that the condition is an acquired metabolic disorder, perhaps occurring in patients abnormally predisposed to such an acquisition.

Cardiomyopathies↗
PubMed1977

Effects of acetylsalicylic acid and indomethacin on growth hormone secretion in man.

To investigate the possibility that prostaglandins (PG) take part in the control of growth hormone (GH) secretion in humans, we have studied the effects of protracted and acute administration of acetylsalicylic acid (ASA) and indomethacin (ID), two PG synthesis inhibitors, on basal and insulin-stimulated GH secretion in normal volunteers. In eight subjects, oral administration of 3-2 g daily of ASA for 4 days clearly reached GH response to insulin hypoglycemia (p less than 0.01, ANOVA). In six additional subjects, GH response to hypoglycemia was not modified by a 4-day oral treatment with 300 mg daily of ID. The pattern of plasma free fatty acids (FFA) and blood glucose during the insulin tolerance test was not significantly affected by ASA treatment. After ID the O time value of the above parameters was somewhat higher than under basal conditions, while the drop of blood glucose, but not to FFA, was slightly more pronounced. Acute oral administration of 1.5 g ASA in 12 subjects did not appreciably modify baseline plasma GH, FFA, and blood glucose levels. By contrast, a single oral dose of 100 mg ID in 12 subjects caused a moderate but significant rise (p less than 0.05) of plasma GH levels together with a clear elevation (p less than 0.01) of plasma FFA and blood glucose levels with respect to a group of controls treated with a placebo. Collectively these results are compatible with the possibility that PG play a physiologic stimulating role in the control of GH secretion, although an effect of ASA and ID unrelated to PG inhibition cannot be ruled out, In any event, in view of the number of endocrine and metabolic alterations induced by ASA and ID, these drugs seem to merit further study.

Adult↗
PubMed1976

Vaccine and Mycostatin in treatment of cryptococcosis of the respiratory tract.

Three cases of respiratory crytococcosis are described, one diagnosed only after thoracotomy and two after cytology. All were confirmed by cultures, biological and biochemical tests. The patients are alive and well 14 years, 5 years, and 5 years after treatment with crytococcal vaccines and mycostatin. Vaccines proved very effective when given intradermally in small doses and no dangerous reactions were encountered. Cytology of the sputum appears to be a very useful tool in diagnosis of fungal infections of the respiratory tract, especially when supravital staining is used. Difficulties in diagnosis, treatment, and significance of positive sputum findings are discussed.

Adult↗
PubMed1976

Local and systemic opsonic adherent, hemagglutinating and rosette forming activity in mice induced by respiratory immunization with sheep red blood cells.

The humoral response in mice after intranasal (IN) instillation of sheep red blood cells (SRBC) was compared to that produced by intraperitoneal route of immunization. Study of opsonic adherent (passive indirect cytophilic) and hemagglutinating antibody levels in serum and bronchial washings after repeated challenge with SRBC showed that serum antibody titers following respiratory immunization does not differ from the general pattern of a humoral antibody response. The bronchial wash antibody titer was higher than the serum titer as calculated per globulin unit. In contrast, the appearance of measurable antibodies in the bronchial washings after repeated intraperitoneal immunization was delayed and in low titer. B. pertussis vaccine administered in conjunction with SRBC was found to be an excellent adjuvant in the intranasal route of immunization. A single administration of SRBC-Pertussis evoked a considerable adjuvant effect as measured by hemagglutinating and opsonic adherent tests. Monospecific anti-mouse IgG nullified the hemagglutinating and opsonic adherent activity of the bronchial washings, while monospecific anti-mouse IgM had no effect in either activity. Lung and spleen cells capable of forming rosettes with SRBC of intranasally immunized and control mice were counted. Mean response on day 14 was 6 X 10(3) rosetes per million lung lymphoid cells in comparison with less than 10(3) in control mice. No difference was found in the number of rosette-forming cells in the spleen of control and intranasally immunized mice.

Adjuvants, Immunologic↗