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Biomedical subjects

C Alarcón

Publications and source records attributed to C Alarcón.

36 records · Page 2Linked to original sources

The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets.

The biosynthesis of proinsulin is specifically stimulated by glucose in the pancreatic beta-cell, and this, in turn, places an increased demand on the mechanism for proinsulin to insulin conversion. Proteolytic proinsulin processing is catalyzed by two endopeptidases putatively identified as the subtilisin-related PC2 and PC3 convertases (Bennett, D. L., Bailyes, E. M., Nielson, E., Guest, P. C., Rutherford, N. G., Arden, S. D., and Hutton, J. C. (1992) J. Biol. Chem. 267, 15229-15236; Bailyes, E. M., Shennan, K. I. J., Seal, A. J., Smeekens, S. P., Steiner, D. F., Hutton, J. C., and Docherty, K. (1992) Biochem. J. 285, 391-394). In this study, we demonstrate in isolated rat pancreatic islets that the biosynthesis of PC3 was specifically stimulated by glucose relatively parallel to that of proinsulin. In contrast, however, PC2 biosynthesis was not glucose-regulated. The stimulation of PC3 and proinsulin biosynthesis was observed above a threshold of 4 mM glucose and reached a maximum (about 7-10-fold) above 10 mM glucose concentrations. Glucose stimulation for PC3 and proinsulin biosynthesis was rapid (occurring within 20 min and reaching a maximum by 60 min) and was not affected by the additional presence of actinomycin D, suggesting regulation predominantly at the translational level. Moreover, the intracellular signals for glucose-stimulated PC3 and proinsulin biosynthesis appeared to be similar, requiring the metabolism of glucose. PC3 has been implicated as the key endopeptidase in proinsulin to insulin conversion, in that it is the enzyme which preferentially initiates the process (Rhodes, C. J., Lincoln, B., and Shoelson, S. E. (1992) J. Biol. Chem. 267, 22719-22727). We suggest that co-ordinate stimulation of PC3 biosynthesis, along with that of its proinsulin substrate, elucidates an additional control point by which the mechanism of proprotein processing might be regulated.

Animals↗

Renal catabolism of truncated glucagon-like peptide 1.

We have searched for the contribution of the kidney to the catabolism of glucagon-like peptide-1 (7-36)amide or tGLP-1 by analyzing the disappearance of the [125I]tGLP-1 both in vivo, from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated (BUL) and normal rats and in vitro from the perfusate of an isolated rat kidney system. Also, we have measured the degradation of the peptide by the isolated renal tubules. Results from in vivo studies demonstrated that the disappearance half-time (t1/2) of [125I]tGLP-1 was significantly lower in the control than in BUL or BNX rats with the metabolic clearance rate (MCR) being higher in the control than in BUL and BNX group; no difference was found for both parameters between BUL and BNX rats. The urinary excretion of the peptide was negligible. The data from the isolated kidney experiments showed a disappearance of the peptide, which was not due to its spontaneous degradation nor to enzymes released from the kidney to the perfusate. Degradation of the peptide also occurred in the presence of isolated tubules. It was dependent upon the concentration of tubules. This could possibly be due to the action of the brush border-associated peptidases. In conclusion, our results demonstrate that, in the rat, the kidney removes the exogenous tGLP-1 from the peripheral circulation, by a mechanism that involves glomerular filtration and tubular catabolism.

Animals↗

Family violence as a determinant factor in juvenile maladjustment.

The family is one of the major socialization agencies for children. Parents are one of the most important models from whom the child and adolescent acquire a wide variety of behavior patterns, attitudes, values, and norms. The aim of this study was to determine the importance of factors related to family conflicts in the genesis of social maladjustment. A total of 189 young people (110 boys and 79 girls) from training schools connected with the juvenile court in Murcia (Spain) were studied. The subjects' ages ranged from 11 to 18 years (mean 13.51, SD 0.16). Our sample comprised a group of minors who experienced a high incidence of intrafamilial pathology, which was found to be a significant discriminant factor. Aggressive behavior, rules, norms, values, opinions, and attitudes toward aggressivity can be learned in the family setting.

Adolescent↗

Personality traits in juvenile maladjustment.

The aim of this study was to establish the role of some personality traits, measured by psychological tests, in minors and adolescents experiencing problems in their social integration. We studied 189 subjects (110 male, 79 female) ranging in age from 11 to 18 years. All the subjects were from centers under the administration of the juvenile court of Murcia, Spain. Each subject underwent individual clinical psychological examination as well as psychometric and psychological studies. Our results show a statistically significant association between the scores on some of the tests used and variables related to familial and social maladjustment. These personality traits define a set of individuals with a characteristic profile, for whom unfavorable biographical events have made integration in, and adaptation to, the established social milieu difficult.

Adolescent↗

Bleeding in acute promyelocytic leukemia (APL): fibrinolysis or defibrination?

The coagulation abnormalities in 20 cases of acute promyelocytic leukemia (APL) treated at a single institution were reviewed. A remarkably uniform picture of defibrination and increased FDPs with well-preserved levels of other coagulation factors including AT-III was seen. Our data, together with those available in the literature, do not support DIC as the underlying mechanism of bleeding but seem rather to point to increased proteolysis as the cause.

Adult↗

Renal catabolism of human glucagon-like peptides 1 and 2.

The renal catabolism of [125I]glucagon-like peptide 1 (GLP-1) and [125I]glucagon-like peptide 2 (GLP-2) has been studied both in vivo, by the disappearance of these peptides from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated (BUL) or normal rats, and in vitro, analyzing their catabolism by the isolated, perfused rat kidney. Results from in vivo studies demonstrated that half-disappearance time for both peptides was lower in controls than in BUL rats, and this value in BUL rats was not significantly different from that in BNX rats. In addition, metabolic clearance rate of GLP-1 was higher in control rats than in the other two groups of animals. Urinary clearance rate of both peptides was negligible. In isolated kidney experiments, values for organ clearance of both [125I]GLP-1 and [125I]GLP-2 were similar to those of inulin clearance, which represents the glomerular filtration rate. Urinary clearance of trichloroacetic acid precipitable radioactivity represented less than 1% of total clearance. In conclusion, these results demonstrate a significant role for the kidney in the plasma removal of [125I]GLP-1 and [125I]GLP-2 by a mechanism that involves glomerular filtration and tubular catabolism.

Animals↗

[Effects of aescine and aesculine on kidney excretion of water and electrolytes in rats].

Effects of aescine and aesculine, active principles of the horsechestnut, on urinary excretion of water and electrolytes, were investigated in saline loaded rats. Results indicate that aesculin shows a moderated diuretic activity, increasing significantly the renal loss of sodium, chloride and potassium. Nevertheless, only the highest dose of aescine caused the same degree of minease in saluresis with aesculin, where a doses-response relationship was observed.

Animals↗

[Chromosomal changes in 60 patients with acute myeloblastic leukemia. Frequency, characteristics and prognostic significance].

Sixty patients diagnosed of acute myeloblastic leukaemia (AML) on whom a chromosomal study was performed at diagnosis were evaluated. Their median age was 43 years (range: 8-89). Normal karyotype was present in 59% of the cases, it being abnormal in the remaining 41%. Chromosomal alterations appeared in 64% of the patients with M-4 morphology, in 43% of M-5, 40% of those with M-1, 33% of the M-2, and in 14% of the cases with M-3 morphology. The two patients with M-6 had abnormal karyotype. No correlations could be established between normal or abnormal karyotype and the clinical or laboratory data. Structural alterations were commonest amongst the patients with abnormal karyotype. Such alterations included t(8; 21), t(9; 22); t(7; 22), del 11q23, inv 16 (p13;q22), plus multiple major abnormalities in the M-6 patients. A strikingly low incidence of t(15; 17) was found in the acute promyelocytic leukaemia cases. Two chromosomal alterations not previously reported in AML were found in this series, namely, inv 13 (p11;q32) and t(21;1) (q22;q22). The finding of an abnormal karyotype had no unfavourable influence on the complete remission (CR) rate, which reached 65% of the patients with normal karyotype and 81% of those with abnormal karyotype. No differences were found in the duration of CR in this connection (80 and 77 weeks, respectively). Despite the lack of definite prognostic significance, the study of the karyotype appears as an important information in the diagnosis of AML.

Adult↗

Intraerythrocytic adaptation to anaemia in thalassaemia.

Red cell 2.3-diphosphoglycerate (2.3-DPG) response to anaemia is evaluated in 83 patients with different types of heterozygous thalassaemias, and 40 patients with chronic ferropenic anaemia and 120 healthy subjects are used as control groups. In heterozygous beta, beta delta, and alpha thalassaemic patients the 2.3 DPG concentration is appropriate for the degree of anaemia present.

2,3-Diphosphoglycerate↗

Effects of Ca++ depletion on the asexual cell cycle of Plasmodium falciparum.

Ca++ was shown to be indispensable for the normal growth of cultures of Plasmodium falciparum. Inclusion of ethyleneglycolbis (beta-amino-ethylether) N,N'-tetra-acetic acid (EGTA) caused blocking of the asexual cell cycle of the parasite in two sites, the first blockage occurring between 20 and 26 hours after invasion of the erythrocyte. It proved to be irreversible by additions of Mg++ or Ca++, and to lead to morphologically abnormal parasites arrested in the mature trophozoite stage of the cycle. The second site of inhibition was probably one of the steps in the process of invasion of the erythrocyte by the merozoite. When 1 mM EGTA was added 24--30 hours after the culture was synchronized the cell cycle of the parasite continued without any interference in the normal maturation until the development of schizonts and release of merozoites into the medium. However, reinvasion of fresh erythrocytes by these merozoites was impeded. The inhibition of reinvasion caused by EGTA was overcome by the addition of an excess of Ca++ but not by an excess of Mg++. After the addition of Ca++ to cultures blocked just before the invasion phase as schizonts, the merozoites were again rendered fully infective and the rate of invasion was similar to that in an untreated control culture. Implications of the effects of Ca++ depletion on the asexual cell cycle and possible applications of EGTA as a reversible inhibitor of the invasion process are discussed.

Calcium↗

Lipolytic action of glucagon-like peptides in isolated rat adipocytes.

The lipolytic effect of GLP-1(1-36)-amide, GLP-1(7-36) amide and GLP-2 [proglucagon(126-159)] has been studied in isolated rat adipocytes. Glycerol release and cyclic AMP content were measured after incubation of adipocytes with GLPs and results have been compared with those obtained in the presence of glucagon. GLP-1(7-36)-amide and GLP-1(1-36)-amide at 10(-8), 10(-7) and 10(-6) M concentrations activated glycerol release, the truncated peptide having a more potent effect. On the other hand, GLP-2 had no effect on glycerol release. Also, it has been found that 10(-6) M GLP-1(7-36)-amide increases cyclic AMP content in adipocytes and does not compete with glucagon binding. These results demonstrate that GLP-1(7-36)-amide has a lipolytic effect on isolated rat adipocytes through different receptors than glucagon.

Adipose Tissue↗

[Ionic dialysance to control the dose of dialysis. One year experience].

The Diascan equipment (Hospal) measures ionic dialysane which it derives the K and the Kt. If we divide the Kt obtained with Diascan between the Kt/V obtained by a simplified formula, it result a value of V for every patient. Entering this V in the Diascan software we can obtain a Kt/V (Diascan Kt/V), similar in theory to the simplified Kt/V. In the year 2002 we have controlled the delivered dialysis in our unit with the Diascan Kt/V. The aim of the present study was to study the agreement between de Diascan Kt/V and the Lowrie Kt/V. During the year 2002, 63 patients have been dialyzed in monitors with Diascan equipment. We calculated the V of each patient by dividing the Kt Diascan between the Lowrie Kt/V in the same dialysis session. The mea of the two consecutive measurements was considered the V value. Throughout the year 2002, 7 agreement studies were realized. The inter-method variability was assessed by the relative difference (absolute difference Diascan Kt/V-Lowrie Kt/V, divided by the average of both tests). A good agreement was considered when the relative difference was equal or lower than 10%. In the 7 agreement studies realized, the mean of the relative difference oscilled between 5.2 and 6.6%, and the percentage of patients with a relative difference equal or lower than 10% oscilled between 83 and 91%. During a month, the Diascan Kt/V was controlled in all dialysis sessions in 41 patients (554 sessions in total). Failure in the lecture of Kt/V Diascan was observed in 41 sessions (7%). A Diascan Kt/V greater than 1 (the minimum delivered dialysis considered in our unit) was obtained in 93% of the valid sessions. 38 of 41 patients had a mean monthly Diascan Kt/V greater than 1. The coefficient of variability of any patient oscilled between 2.1 and 12.4% (mean 5.1%). Diascan Kt/V is good procedure for the monitoring the delivered dialysis without blood sampling or any additional costs.

Evaluation Studies as Topic↗