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Biomedical subjects

A Tavares

Publications and source records attributed to A Tavares.

At least 19 recordsLinked to original sources

Severe hypertension induces disturbances of renal autoregulation.

To study if the severity of hypertension could be associated with disturbances of the autoregulation of renal blood flow and glomerular filtration, we compared the renal hemodynamic and functional responses to acute blood pressure reductions of a group of patients with moderate essential hypertension (n = 10) with those of a group of patients with severe hypertension (n = 10). Blood pressure was reduced to normal levels by a stepwise infusion of sodium nitroprusside, and effective renal blood flow (by 131I-hippuran), glomerular filtration rate (by endogenous creatinine clearance), and filtration fraction were determined. After acute blood pressure normalization, effective renal blood flow and glomerular filtration rate were significantly reduced in patients with severe hypertension (-41.6 +/- 8.3% and -44.7 +/- 6.8%, respectively; p less than 0.01 for both) but not in those with moderate hypertension (+4.9 +/- 9.1% and +6.2 +/- 13.3%, respectively; NS). Filtration fraction remained unchanged in both groups. These results show that severe but not moderate essential hypertensive patients have a displacement to the right of the lower limit of the renal autoregulation curve due to impaired vasodilation to maintain adequate renal blood flow during acute reductions of blood pressure. This impairment may be due to anatomic or functional defects of preglomerular vessels, or to both. Furthermore, the inability to maintain adequate glomerular filtration in these circumstances shows that patients with severe hypertension also have an impaired ability to adjust postglomerular vasomotor tone in the face of reductions in glomerular blood flow.

Adolescent

[Safety in hemophilia A treatment. Viral inactivation of FVIII:C concentrates].

In the last thirty years, factor VIII concentrates have been the mainstay of hemophilia treatment, first as wet cryoprecipitate and later as dry concentrates commercially available. The evidence of a high risk of blood-born virus transmission by these products provoked the development of new methods for virus inactivation. We report these methods with special attention to their safety, and mention the new perspectives of treatment with recombinant DNA FVIII:C and ultimately by gene insertion therapy.

Factor VIII

[Methods for preserving bone marrow for autologous transplantation].

For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.

Adolescent

polo encodes a protein kinase homolog required for mitosis in Drosophila.

We show that mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed; normal bipolar spindles with polyploid complements of chromosomes; bipolar spindles in which one pole can be unusually broad; and monopolar spindles. We have cloned the polo gene from a mutant allele carrying a P-element transposon and sequenced cDNAs corresponding to transcripts of the wild-type locus. The sequence shows that polo encodes a 577-amino-acid protein with an amino-terminal domain homologous to a serine-threonine protein kinase. polo transcripts are abundant in tissues and developmental stages in which there is extensive mitotic activity. The transcripts show no obvious spatial pattern of distribution in relation to the mitotic domains of cellularized embryos but are specifically concentrated in dividing cells in larval discs and brains. In the cell cycles of both syncytial and cellularized embryos, the polo kinase undergoes cell cycle-dependent changes in its distribution: It is predominantly cytoplasmic during interphase; it becomes associated with condensed chromosomes toward the end of prophase; and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic.

Amino Acid Sequence

Demonstration of three calpains in the matrix of rat liver mitochondria.

Three distinct Ca(2+)-activated proteolytic activities could be proven in rat liver mitochondria. The proteolytic activities detected in the presence of Ca2+ are different in the two mitochondrial soluble compartments, the matrix and the intermembrane space. Strikingly three Ca(2+)-activated proteolytic activities (M1, M2 and M3) appear in the matrix whereas the intermembrane space contains only two such activities. These proteolytic activities are similar to the calpains already described in the cellular cytosol with regard to their optimal pH and inhibition profiles. The Ca2+ requirements for activation of M1 and M2 correspond to those of the micromolar and millimolar Ca(2+)-requiring proteinases, whereas the concentration of Ca2+ required to activate M3 is an intermediate value.

Animals

Pindolol, not propranolol, reverses cardiac hypertrophy in renal hypertensive rats.

Reversal of cardiac hypertrophy has been obtained by treatment with some antihypertensive drugs but has not been achieved consistently with beta blockers. To investigate whether this difference might be explained by the distinct hemodynamic actions of the drugs, we studied the effects of propranolol and pindolol, beta blockers with distinct modes of action, on cardiac hypertrophy of hypertensive male Wistar rats, two-kidney, one clip (2K1C) Goldblatt model (n = 33) and sham-operated control rats (n = 34). We also assessed the effects of such therapies on the ventricular pumping ability during open-chest, transient aortic occlusion. Four weeks after surgery, propranolol (5 mg/kg/day p.o.) was given to hypertensive (n = 8) and control rats (n = 11); pindolol was also given orally (1 mg/kg/day) to similar groups (n = 7 and n = 5, respectively). Untreated animals served as controls for both groups. Cardiac hypertrophy developed with hypertension in the untreated rats of the propranolol (3.38 +/- 0.18 vs 2.60 +/- 0.08 mg/g; p less than 0.01) and pindolol groups (3.93 +/- 0.21 vs 2.40 +/- 0.03 mg/g; p less than 0.001). Treatment reversed cardiac hypertrophy in the pindolol-treated (3.01 +/- 0.19 vs 3.93 +/- 0.21 mg/g; p less than 0.001, NS) but not in the propranolol-treated rats (3.24 +/- 0.18 vs 3.38 +/- 0.21 mg/g, NS). The maximal pressure that developed during aortic occlusion in the propranolol group was similar to that observed in the pindolol group. These results indicate that cardiac hypertrophy is reversed by pindolol but not by propranolol, and that this reversal does not interfere with left ventricular pumping ability.

Animals

31P-NMR study of the orotate phosphoribosyltransferase equilibrium with thiopyrophosphate as substrate.

31P-nuclear magnetic resonance spectroscopy was used to directly determine the equilibrium of the reaction catalysed by yeast orotate phosphoribosyltransferase, using orotidine monophosphate and inorganic pyrophosphate as substrates. A Keq value of 0.71 was determined, in good agreement with that of 0.49 calculated by Victor, Greenberg and Sloan (J. Biol. Chem. 254 (1979) 2647-2655), from kinetic data. Substitution of thiopyrophosphate as the substrate shifted the position of the equilibrium 55-fold, to yield a Keq value of 39. Only the beta S analogue of 5-phosphoribosyl 1-diphosphate appeared to be synthesized in this reaction.

Diphosphates