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B Castro

Publications and source records attributed to B Castro.

87 records · Page 5Linked to original sources

Renin inhibition by synthetic peptides related to mouse and human renin prosegments.

Recently the nucleotide sequences of the genes coding for mouse and human renins have been elucidated and the primary structures of the corresponding renin precursors deduced. The existence of a prosegment suggests that renin is biosynthesized as an inactive zymogen prorenin. Three peptides related to the region 11-19 of the mouse submaxillary prosegment have been synthesized and tested as inhibitors of pure mouse renin acting on a synthetic porcine substrate. Inhibition of renin activity was effective, with IC50s in the 10(-6) M range. Butyloxycarbonyl-leucyl-lysyl-lysyl-methionyl-proline methyl ester (15-19) was the most potent inhibitor with a K value of 2.3 X 10(-6) M at 37 degrees C in 0.5 M citrate/phosphate buffer (pH 6.0). Peptides 16-20 and 9-20 of the human renin prosegment and peptides 11-19 and 15-19 of the mouse prosegment were tested on human plasma renin activity and found to be inhibitory, with IC50s of 3 to 5 X 10(-4) M. These results demonstrate that the renin prosegment is a renin inhibitor and support the hypothesis that prorenin is an inactive zymogen.

Animals↗

[Diarrhea caused by Campylobacter fetus jejuni and other infective agents in children of the rural area of Puriscal, Costa Rica].

Between September 1979 and September 1981 a field study was conducted on the etiology of diarrheal disease in the area of Puriscal, Costa Rica. The presence of enteric pathogens was investigated in the stools of 267 diarrheic children and 190 healthy controls. Both groups belong to yearly cohorts recruited at birth as part of a longitudinal multidisciplinary study of mothers and children. Campylobacter fetus jejuni was identified as the only pathogen in the stools of 24 diarrheic children (9%) and in four healthy controls (2%), a significant difference (p less than 0,05). The clinical features of the episodes were: irritability (77%), blood in stools (35%), anorexia (38,5%), and fever and vomiting (36%). Dehydration was not important among infected children (only one with 5% dehydration). All children received oral salt solutions and only two were treated with antibiotics. Rotaviruses were the main etiologic agents (17%) and Campylobacter ranked second (10,5%). The frequency of enterotoxigenic Enterobacteriaceae was similar in sick children and in controls (10% and 12% respectively).

Anti-Bacterial Agents↗

[Thin layer immunoassay (TIA). A rapid and simple method for the serodiagnosis of echinococcosis (author's transl)].

The specificity, reproducibility and value of the diagnosis of echinococcosis in the thin layer immunoassay test were determined by the study of 147 human sera. With the reagents used this reaction was specific for serum dilutions of 1/8 or more. Its reproducibility, confirmed on 4 occasions in a series of 60 sera was satisfactory and its diagnostic value in 40 cases of proven hepatic echinococcosis led to 32 positive results (80% of cases). Comparison with indirect haemagglutination, indirect immunofluorescence, electrosyneresis (32 sera) and the ELISA test showed the excellent degree of complementary behaviour of the different reactions. By contrast, the study of sera obtained from two patients at different times after surgical treatment did not show serological peaks similar to those usually seen by indirect immunofluorescence. By virtue of its ease, rapidity and low cost, thin layer immunoassay could no doubt represent in echinococcosis if not a very precise diagnostic test, at least a means of detection suitable for wide use.

Echinococcosis↗

New renin inhibitors homologous with pepstatin.

Four homologues of pepstatin, the potent but poorly soluble inhibitor of aspartic proteinases, were synthesized by coupling to the C-terminus of the natural pentapeptide the following amino acid residues: L-arginine methyl ester, L-aspartic acid, L-glutamic acid and the dipeptide L-aspartyl-L-arginine. The peptide-coupling reagent we used, benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate, allowed us to obtain readily pure pepstatin homologues with high yields (60-83%). Pepstatylarginine methyl ester and pepstatylglutamic acid were about one order of magnitude more water-soluble than pepstatin. The four homologues and pepstatin were tested in vitro as inhibitors for highly purified pig and human renins acting on the N-acetyltetradecapeptide substrate. The 50% inhibitory concentrations (IC50) of the homologues were ranged from 0.01 to 1 microM against porcine renin at pH 6.0 (pepstatin IC50 approximately 0.32 microM) and from 5.8 to 41 microM against human renin at pH 6.5 (pepstatin IC 50 approximately 17 microM). By three different graphical methods we showed that pepstatin and the four homologues behaved as competitive inhibitors for porcine renin. The most potent inhibitors were pepstatylaspartic acid and pepstatylglutamic acid, with inhibitory constants respectively 2- and 10-fold smaller than that of pepstatin. By coupling glutamic acid to pepstatin, the ratio solubility/Ki was increased by two orders of magnitude.

Animals↗

[Preparation of antisera against some sequences of somatostatin synthetized on resin. Application to the immunological detection of somatostatin systems: preliminary results (author's transl)].

Specific SRIF(1-14) fragments were synthetized on resin using conventional procedures. Rabbits received subcutaneously peptidyl resins in complete Freund adjuvant emulsion. The presence of antibodies was assessed by immunocytochemical and radioimmunological assays. 1. Peptidyl resins lead to antibodies production; their specificity depends on sequence and molecular configuration of the peptide on the resin. Anti-resin antibodies were not detected. 2. In the brain, SRIF(1-4) (in rat) and SRIF(10-13) (in garden-dormouse) can be demonstrated in neurophysins--positive cells of both paraventricular and supraoptic nucleus, but never in hypothalamic or extrahypothalamic SRIF(1-14)--positive neurophysin negative cells. 3. Endocrine cells of pancreatic islets contain SRIF(6-9) (in man) or SRIF(10-13) (in rat, mouse, garden-dormouse); generally, these cells are not detected by SRIF(1-14) anti-serum. Moreover, SRIF(10-13) positive cells are also detected by specific glucagon antibodies. However, it cannot be concluded that SRIF(10-13) antibodies reveal the common Thr-Phe-Thr-Ser fragment in the entire glucagon molecule. It is postulated that antibodies to several SRIF tetrapeptides reveal molecular fragments provided by the functional cleavage of an hypothetical prohormone or by the inactivation of SRIF(1-14) molecule in target cells.

Animals↗

Soluble pepstatins: a new approach to blockade in vivo of the renin-angiotensin system.

1. Synthesis of several pepstatin A derivatives was performed with the aim of increasing water solubility without altering the capacity to inhibit the renin-angiotensinogen reaction. 2. Pepstatinyl-arginine-O-methyl ester was studied in vitro and in vivo and compared with pepstatin A and with the arginine salt of pepstatin A. 3. This compound inhibited in vitro the reaction between purified hog renin and the synthetic renin N-acetyl-tetradecapeptide or the natural rat renin substrate. The inhibitory constant was of the same order of magnitude as that of pepstatin A. 4. In renal hypertensive rats, the bolus injection of pepstatinyl-arginine-O-methyl-ester or of the arginine salt of pepstatin decreased blood pressure to the same extent as a bolus injection of Sar1, Ala8-angiotensin II.

Animals↗

Molecular recognition between serine proteases and new bioactive microproteins with a knotted structure.

Microproteins with proteinase inhibitory activity, 28 to 30 amino acids long, with 3 disulfide bridges have been isolated from Ecballium elaterium seeds. A peptide (EETI II) was isolated and behaved as a powerful trypsin inhibitor (Kd = 10(-11) to 10(-12) M). It was sequenced, chemically synthesized and the 3-D structure determined by 2-D 1H NMR. The information gained in the process enabled us to synthesize modified derivatives with inhibitory activity towards pancreatic elastase, chymotrypsin and human leucocyte elastase (Kd = 10(-7) to 10(-9) respectively). The most striking characteristic that appeared during the synthetic approach was the unfailing ability of the 28 amino acid peptides to refold and correctly close the 3 disulfide bridges, giving in each case an active compound. These disulfide bridges are assembled in a particular knotted structure, shared by few other bioactive peptides and called the 'knottin' structure. Molecular modeling of the peptide and a comparison with the other active molecules with similar topology allowed the synthesis of a chimaeric peptide, bearing 1 active site against a seryl-protease (trypsin), and 1 against a metallo-protease (carboxypeptidase A). The bis-headed peptide was able to inhibit both enzymes separately and concomitantly.

Amino Acid Sequence↗

Synthesis and renin inhibitory properties of a new soluble pepstatin derivative.

A new pepstatin derivative, pepstatinyl arginine methyl ester hydrochloride (pepstatinyl-Arg-O-Me), was synthesized with the aim of increasing water solubility without altering capacity to inhibit the renin-angiotensinogen reaction. Pepstatinyl-Arg-O-Me was shown to inhibit in vitro the reaction between either rat or purified hog renin and the natural rat renin substrate. In a fluorimetric assay, this derivative competitively inhibited the reaction between purified hog renin and a synthetic N-acetyl-tetradecapeptide renin substrate with a Ki of the same order of magnitude as that of pepstatin. In urethaneanesthetized ganglion-blocked rats, binephrectomized 24 hr before the experiments, both the plasma reinin concentration and the rise in blood pressure following intravenous injection of hog renin were inhibited by pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-O-Me inhibited the 1.4 mumoles/kg. The in vivo inhibitory effect of 1.4 mumoles/kg of pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-Op-Me inhibited the reaction of endogenous and exogenous renin with plasma substrate both in vitro and in vivo.

Angiotensin II↗

Tunicamycin treatment reduces intracellular glutathione levels: effect on the metastatic potential of the rhabdomyosarcoma cell line S4MH.

Highly metastatic cells are known to overexpress certain Asn-linked oligosaccharides in the plasmatic membrane. Another phenotypic characteristic of malignant cells consists in the expression of high levels of intracellular glutathione (GSH). The aim of the present work was to demonstrate that the inhibition of N-glycosylation induces changes in intracellular GSH levels, and in turn participates in the inhibition of the metastatic potential of tumor cells by tunicamycin treatment. Firstly, we demonstrated that in comparison to the poorly metastatic cell line F21, the highly metastatic cells S4MH express a higher number of Asn-linked beta1-6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins involved in the regulation of the adhesion efficiency of tumor cells on endothelial cells and extracellular matrix. Our results showed that the decrease in S4MH cell adhesion efficiency on endothelial cells and extracellular matrix after the inhibition of N-glycan processing by tunicamycin treatment was caused by: (1) inhibition of the expression of N-glycan structures recognized by endothelial endogenous lectins, including beta1-6 branched oligosaccharides and SA and/or chitobiose oligosaccharides, and (2) redistribution of cell surface glycoproteins with beta1-6 branched oligosaccharides and/or SA and/or chitobiose oligosaccharides in their structures, caused by the depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cells necessary for anchoring to the substratum.

Actins↗

[Psychology and cancer: role of rationalization in cancerous disease of unfavorable prognosis (apropos of a clinical case)].

This text intends to tackle one of the aspects of psychosomatic interactions in cancer: the patient's irrational cognitions related to his trouble. The authors design as cognitive process (CP) the mental work implying the production and the evolution of personal cognitions bound to a personal event. In cancer, CP often drives the subject to adopt irrational points of view concerning his disease, which onset is readily described as a consequence of significant life events; in such explanations, the part of hazard is excluded. The authors suggest that spontaneous CP may be useful helping the patient to avoid strong depressive affects, to alleviate feelings of anger or despair and to improve self-esteem threatened by the illness. The authors consider that using CP concept may be an accurate tool in psychotherapy of patients suffering from cancer. Therapeutic strategies may tend to favour the CP development so that the subject's conceptions stabilize on an ego-syntonic level.

Attitude to Death↗

[Deinstitutionalization and modern history].

The authors trace the history of ideological or socio-economical-political conditions of desinstitutionalisation. They try to analyse the consequence of it about the constitution of a new pathology of homeless and careless chronic mental ill. This pathology was described first in the states and Canada. It begins to be described in France. The authors go on to show it's a new kind of mental pathology, needing to take place in the new classifications of mental illness.

Canada↗

[Apropos of a misdiagnosed form of paranoia: paranoia of the elderly].

The expression of elements of a paranoid symptomatology (suspicion, mistrust, hostility, etc.) is frequently seen in the elderly patients. Paranoid symptom is non-specific in geronto-psychiatric practice. The association with a cognitive disorder is frequent. The relationship between this trouble and a previous paranoid personality disorder appears, according to literature, looser than in the younger patients. The paranoid behavioral pattern often stands for the elderly as a defense against feelings of inferiority and humiliation. The expression of a paranoid symptomatology is a hamper for the subject's social autonomy, as well as an actual risk factor so far as it may involve a delay in the demands for medical care. Therapeutical attitudes, reassurant and preventing the patient from a rough awareness of his deficit, seem to be useful in the alleviation of the trouble.

Aged↗

[Use of role-playing in child psychotherapy and psycho-pedagogy].

Spontaneous role-playing in children stands as a contribution in generating and in improving social behaviors. Spontaneous role-playing is a part of the child's maturing process. Its characteristics: it does not follow any logical pattern; it is frequently repeated; its emotional involvement is important, without ambivalence. Educational role-playing attempts to help the child in coping with a peculiar interpersonal situation. Therapeutical role-playing may be used in helping children suffering from a definite impairment of social skills--or from any psychological or medical problem. We report an example of the use of therapeutical role-playing in a group of diabetic children suffering from disorders in interpersonal relationships arisen at the time of the onset of their physical illness.

Adolescent↗