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Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 217 records · Page 12Linked to original sources

Insulin and glucagon production in experimental cirrhosis.

The release of insulin and glucagon in cirrhotic rats was examined. Rats were made cirrhotic by a combination treatment of carbon tetrachloride (CCl4) and phenobarbitone. Liver cirrhosis was verified by histologic findings. Both basal and stimulated release of insulin from isolated pancreatic islets, in vitro, were decreased significantly in cirrhotic rats, as compared with control rats. Basal, but not stimulated, levels of glucagon, in vitro, were reduced significantly in cirrhotic rats. Circulating levels of plasma insulin, glucagon, glucose, bilirubin, and amylase levels were unaffected in cirrhotic rats when compared with control rats. There were no signs of pancreatitis. The results indicated that the release of insulin and glucagon is depressed in cirrhotic rats and in rats treated with phenobarbitone and CCl4. Clearance of circulating insulin and glucagon by the liver was apparently reduced, since circulating levels of insulin and glucagon were unaltered in all treated rats.

Animals↗

Triiodothyronine regulation of multiple rat hepatic genes: requirement for ongoing protein synthesis.

We have examined the role of rapidly turning over proteins in the T3 regulation of multiple rat hepatic genes. T3 induction of the rapidly responsive mRNA-S14 was markedly inhibited by cycloheximide (1 mg/100 g BW) or emetine (3 mg/100 g) injected ip 30 min before T3 (mRNA-S14 concentration was only 35% of that in T3-treated controls 8.5 h after administration of either protein synthesis inhibitor, P less than 0.01). Cycloheximide exhibited a similar effect on each of five other more slowly responsive T3 regulated genes. When cycloheximide was given 10 h after T3, the expected T3-induced rise of mRNA-S7 activity was completely prevented, and for mRNA-S4 activity the anticipated rise was blunted to 40% of T3-treated control (P less than 0.05). Cycloheximide caused sharp declines in the activity of two other mRNAs, S6 and S8, which because of shorter lag times of response to T3, had already risen when the drug was given. Values for both these mRNAs returned to the baseline hypothyroid level within 6 h of injection of the drug and remained low for a further 8 h (P less than 0.05). The expected deinduction of mRNA-S10 by T3 was also markedly modified. T3 lowered this mRNA to 11% of the hypothyroid control after 8 h, whereas cycloheximide given 30 min before the hormone blunted this fall to only 72% of control (P less than 0.01). Thus there appeared to be a 70% reduction in the rate of T3 induced fall of mRNA-S10. We did not find that cycloheximide caused a generalized decrease in poly (A)+ RNA mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cycloheximide inhibits S-14 gene transcription and abolishes DNase I hypersensitive S-14 sites in the livers of euthyroid but not hypothyroid rats.

Earlier studies from our laboratory have demonstrated that cycloheximide administration to hypothyroid rats inhibited the induction of the hepatic mRNA-S14 by T3. These results suggested a role of short-lived proteins in the hormonal regulation of this gene. To define the possible mechanism of the cycloheximide effect, we examined the influence of cycloheximide on the in vitro transcription rate of the gene and its chromatin structure. Forty-five minutes after injection of cycloheximide to euthyroid rats, the in vitro transcriptional rate fell by 60% and this effect persisted for 4 h. In the same euthyroid rats, cycloheximide caused the disappearance of all four DNase I-hypersensitive sites situated in the 5'-flanking region of the gene. However, cycloheximide given to hypothyroid rats affected neither the basal transcription rate nor the chromatin structure. When cycloheximide was administered 30 min after an acute injection of T3 (200 micrograms/100 g BW) to hypothyroid animals, it completely blocked the hormone induction of the transcriptional rate. These results suggest that one or more labile proteins are required for maintenance of S14 chromatin structure in a configuration which permits hormonal regulation of gene expression. The ability of cycloheximide to block mRNA-S14 induction by T3 appears to be mediated at least in part by an inhibition of T3-stimulated transcription.

Animals↗

Immunopharmacological effects of Saccharomyces boulardii in healthy human volunteers.

Investigation of oral administration of Saccharomyces boulardii in healthy volunteers demonstrates several cellular and humoral changes in peripheral blood. Among its effects are the increase of erythrocytes, leucocytes, polymorphs, neutrophils, complement components C3, C5, C3d, serum anticomplementary activity and leucocyte chemokinesis, specially when autologous serum and antigen have been added to the culture medium and decrease of complement haemolytic activity (CH50, classic and alternative pathways). We have also demonstrated that in vitro S. boulardii was able to activate complement directly, to fix C3b to its surface and that its phagocytosis by mononuclear cells was complement-dependent. The overall changes in serum proteins suggested changes of acute phase proteins typical of an inflammatory process. Furthermore S. boulardii had no mitogenic response of lymphocyte populations. Our results demonstrated that S. boulardii activates the reticuloendothelial system and complement system and suggest that S. boulardii merits therapeutic trial in a variety of clinical situations.

Adult↗

Repair of atrioventricular septal defects in infancy.

Fifteen infants less than 12 months of age with complete atrioventricular septal defects underwent repair of the defect between January, 1981, and December, 1984. The average age at operation was 8 1/2 months and the average weight was 5.7 kg. Eight of 15 (53%) infants had preoperative mild to moderate mitral insufficiency. Pulmonary artery hypertension was present in all infants and 13 of 15 infants had a pulmonary arterial resistance greater than 4 units (mean 8.8 units). Operative indication was based on pulmonary artery hypertension, congestive heart failure, and failure to thrive. Ventricular distention was utilized during operative repair to assess location of valve incision, level of attachment of valves to the patch, and cleft approximation. It was also used to check the competency of the mitral repair once complete. The average circulatory arrest time was 55.7 minutes. There were no operative deaths. There were two late deaths. We conclude that ventricular distention is the key to the operation, and operative repair is safe in infants with atrioventricular septal defects.

Atrioventricular Node↗

Prenatal intramedullary gliofibroma. A light and electron microscope study.

A case of an unusual congenital intramedullary tumor of the spinal cord is reported. A paraplegic 11-day-old boy with hypotonia and atrophy of the abdominal and lower-extremity muscles showed a complete myelographic block between T-5 and T-8. Surgical exploration disclosed an elongated tumor mass within the spinal cord, that blended with the surrounding nervous-system tissue. Light and electron microscopy showed that the tumor was composed of intermingled well differentiated astrocytes and fibroblasts. These two cell types often were surrounded by the same basal lamina. There were no intercellular junctions. Gliofibrils were abundant, and the interstitial spaces contained abundant collagen and reticulin fibers. There were no histological signs of malignancy. We conclude that this is a case of prenatally arising gliofibroma.

Humans↗

The detection of a platelet-agglutinating factor in thrombotic thrombocytopenic purpura.

A sensitive and specific test was used to identify a platelet-agglutinating factor in sera from patients with thrombotic thrombocytopenic purpura. Serum from patients plus a preparation rich in large multimers of factor VIII: von Willebrand factor were added to target platelets, and agglutination occurred in 41 of 48 samples. Edetic acid, heparin, or heating, but not aspirin, monomeric IgG, or dansylarginine N-(3-ethyl-1,5-pentanediyl)amide inhibited the platelet-agglutinating factor. In-vitro agglutination requires the presence of a platelet-agglutinating factor and large multimers of von Willebrand factor. High concentrations of either component lowers the amount of the other required for platelet agglutination. Some patients may be more susceptible to the agglutinating factor because of a congenital or acquired abnormality in processing unusually large multimers of von Willebrand factor or because of infections or inflammatory disorders that lead to increased synthesis of large multimers of von Willebrand factor.

Adult↗

Hyperbaric bupivacaine for spinal anesthesia in cesarean section.

The efficacy and safety of 0.5% hyperbaric bupivacaine (Sensorcaine, Astra) was evaluated in 22 patients undergoing elective cesarean section under spinal anesthesia. The dose varied from 7.5 to 10 mg, (depending on the patient's height) which was significantly lower than previously reported. Patients were placed in head-down tilt immediately after subarachnoid injection. The mean spread of analgesia was to T3, which was reached in 10-15 min. Regression was complete in 258 +/- 16 min. Complete motor paralysis of lower extremities occurred in only two patients. Complete recovery of motor function in all patients was evident in less than 2.5 h. All infants were vigorous at birth and there were no serious maternal complications. The incidence of hypotension was 4.5%, the lowest reported as a consequence of spinal anesthesia in this group of patients. A technique involving the use of reduced doses of hyperbaric bupivacaine (0.5%) in conjunction with head-down tilt appears to be useful for spinal anesthesia for cesarean section.

Adult↗

Regulatory effect of glucagon on its own receptor concentrations and target-cell sensitivity in the rat.

To evaluate the role of glucagon on its hepatocyte receptor concentrations, groups of rats were injected with a long-acting glucagon preparation (20 [G-20], 40 [G-40] or 60 [G-60] micrograms/100 g body weight) every 8 h for 4 days. Glucagon receptors in liver plasma membranes of treated animals were decreased in number (control = 1.66 +/- 0.20 ng/0.5 mg protein versus G-20 = 1.24 +/- 0.26, G-40 = 1.03 +/- 0.26, G-60 = 0.70 +/- 0.03 ng/0.5 mg protein; p less than 0.05, less than 0.001, less than 0.001, respectively), but they were indistinguishable from receptors of control rats by other criteria including affinity and kinetics of association. Degradation of both glucagon and receptor sites did not account for differences observed in binding. Similar results were obtained with isolated hepatocytes. In relation to controls, isolated hepatocytes of treated rats had a reduced number of receptors (control = 0.70 +/- 0.05 versus G-40 = 0.47 +/- 0.04 ng/10(6) cells; p less than 0.02) proportionate to the decreased glucagon-stimulated production of cyclic AMP and glucose. Four to eight hours exposure of cultured hepatocytes of nontreated rats to 4 x 10(-8) mol/l glucagon produced a decreased binding of 125I-glucagon to its receptor (p less than 0.05). In contrast, hormone exposure for shorter periods of time (0-2 h) was without effect. These results suggest (1) an inverse relationship between circulating glucagon levels and hepatocyte glucagon receptor concentration, and (2) a direct relation between receptor number and target-cell response.

Animals↗