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Biomedical subjects

C F Wolf

Publications and source records attributed to C F Wolf.

At least 37 records · Page 2Linked to original sources

Hepatic sulfhydryl content under adrenergic stimulation in male rats.

The influence of a series of sympathomimetic agents on the liver content of non protein bound thiol groups (NP-SH), mainly representing glutathione, has been assessed in the male rat. The rats were intravenously and/or subcutaneously infused over 6 h at different dosages either with dopamine, dobutamine, epinephrine, terbutaline, or phentolamine, or simultaneously with dopamine and phentolamine, or with epinephrine and phentolamine. Besides NP-SH, total sulfhydryl group content was measured in liver cytosol, while glucose and insulin concentrations were determined in the serum. Liver NP-SH content was significantly decreased by epinephrine. This decrease was abolished and even inverted to an increase, when appropriate doses of phentolamine were infused simultaneously. Dopamine caused a rise in NP-SH content at a dose rate of 7.5 micrograms/kg.min, while lower and higher dose rates of dopamine exerted not any influence on liver NP-SH. When phentolamine was concomitantly infused with 15 micrograms/kg.min of dopamine, NP-SH was significantly elevated. Phentolamine, when infused exclusively, increased NP-SH as well, while it was not influenced, however, by terbutaline or dobutamine at any dosage. Cytosolic total sulfhydryls were found to be unaltered across all experimental groups. When the NP-SH values are related to the corresponding serum insulin levels, a close and linear relationship becomes evident. The study demonstrates, that some sympathomimetic agents can exert a considerable influence on hepatic non protein bound thiol content. The data suggest, that the varying liver NP-SH content under adrenergic drugs is primarily related to changes in serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential effects of dopamine on glucoregulatory hormones in rats.

The effect of dopamine at different doses on serum concentrations of insulin, glucose and corticosterone and on plasma glucagon concentration was investigated in rats. Dopamine was given intravenously over 6 h with infusion rates of 2.5, 7.5, 15, and 60 micrograms/kg.min and in combination with phentolamine. Serum insulin concentration was unchanged at low doses of dopamine. It was significantly increased from 6.0 +/- 0.7 ng/ml to 13.7 +/- 2.3 ng/ml (P less than 0.01) when 7.5 micrograms/kg.min of dopamine were used, whereas it was significantly depressed to 3.96 +/- 0.89 and to 4.0 +/- 0.34 ng/ml (P less than 0.01), respectively, at the high doses of dopamine. This latter effect could be reversed to 6.7 +/- 1.19 ng/ml and inverted to 9.2 +/- 1.7 ng/ml (P less than 0.01) by simultaneously applied phentolamine at appropriate dosages. Serum glucose levels were markedly elevated from 154 +/- 7 to 234 +/- 42 mg/dl (P less than 0.01) by the higher doses of dopamine. A significant alteration of glucagon plasma concentrations from 18.9 +/- 2.8 to 42.3 +/- 14 pg/ml (P less than 0.01) was elicited only by 7.5 micrograms/kg.min of dopamine. The data clearly demonstrate that exogenous dopamine acts differently on glucose homeostasis according to the dosage. The study provides strong evidence that dopamine decreases insulin levels via alpha-adrenergic receptor stimulation. This effect may contribute to the deterioration of glucose homeostasis with high doses of dopamine.

Animals↗

The influence of circulating thyroxine serum concentration on hepatic thyroxine deiodinating activity in rats.

The influence of varying thyroid metabolic states, induced by thyroxine (T4) application, upon type I T4 deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T4 at various doses, ranging from 0 to 50 micrograms/kg b.w. Microsomal T4 to triiodothyronine (T3) deiodinating activity (5'DA) and T4 to reverse T3 (rT3) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T4, T3, and rT3 were measured in the serum. In the experimental rats, T4 serum concentrations ranged from 1.3 micrograms/dl to 15.6 micrograms/dl (controls, 5 +/- 0.2 micrograms/dl, mean +/- SEM), T3 varied between 33 ng/dl and 150 ng/dl (91 +/- 3 ng/dl), and rT3 between 2 ng/dl and 25 ng/dl (7 +/- 2 ng/dl). Relating T4 to T3 serum levels, a curvilinear relationship (power function, r = 0.94, p less than 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T4 and rT3 serum levels (r = 0.75, p less than 0.001). Individual 5'DA increased by more than fourfold, from 531 pg/mg.min to 2,234 pg/mg.min (controls, 1,419 +/- 67 pg/mg.min), when passing from low to high T4 serum values. The increase in 5'DA was steeper in the low T4 range, while it was progressively flattened under T4 levels above the controls' range. The particular changes in 5'DA can be illustrated by calculating the ratio of 5'DA and T4 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glucoregulation under beta-adrenergic stimulation by dobutamine and terbutaline in the male rat.

The influence of the beta-adrenoreceptor stimulating agents dobutamine and terbutaline as compared to epinephrine on insulin and glucose levels has been assessed in the male rat. All agents were infused either intravenously or subcutaneously over 6 h at varying dosages. In addition, epinephrine was given concomitantly with the alpha-adrenoreceptor blocker phentolamine. The heart frequency as an estimate of the effects of the adrenergic agents beyond the glucoregulatory system was accelerated in a dose-dependent manner. Serum insulin concentrations were significantly increased by phentolamine and significantly depressed by epinephrine, while they were virtually unchanged at any dosages of dobutamine, terbutaline, or epinephrine, when simultaneously applicated with phentolamine. As for serum glucose levels, these agents, again, did not exert any influence, while glucose levels were significantly depressed under phentolamine and significantly increased under epinephrine application. The data demonstrate, that dobutamine and terbutaline at pharmacologically common dosages do not affect glucose homoeostasis. The study does not support a major effect of beta-adrenergic stimulation on the pancreatic B cell in the male rat.

Adrenergic beta-Agonists↗

Liver thiol content under varying glucoregulatory states in rats.

The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels.

Animals↗

Donation of blood by the pregnant patient for autologous transfusion.

A study was conducted to determine the safety and utility of autologous blood donation in third trimester pregnancy. Thirty-seven obstetric patients, 32 with an obstetric risk factor, donated an average of 485 ml of blood. Twenty-one of the 37 patients were expected to undergo cesarean section. Nonstress testing was performed before and after phlebotomy. Continuous fetal heart rate monitoring was maintained throughout the donation, which lasted an average of 9 minutes. All nonstress test results were normal before and after the phlebotomy except in one case. All fetal heart rates remained stable during phlebotomy and premature labor was not precipitated. All fetal outcomes were normal. One patient delivered on the day of phlebotomy, 6 hours after the procedure. Only one of the autologous units was used, in a patient who had a pelvic infection and moderate anemia. The incidence of primary cesarean section was 35%. Phlebotomy of the mother appears to be safe for the fetus at term. Further investigation is needed to determine the safety of removal of more than 1 unit of blood and blood donation at earlier gestational ages.

Adult↗

Design and fabrication of a capillary cell culture chamber for the study of convective flow.

The use of capillary culture chambers as artificial pancreas and artificial liver devices would be aided by an improved ability to control the movement of molecules through the capillary walls. The modeling and analysis of the flow and mass transfer in capillary cell culture chambers in which cultured mammalian cells are grown to form masses with tissue density in the extra-capillary spaces is desirable as a basis for scaleup and optimization of the particular microenvironment. The relative roles of diffusion and ultrafiltration with convection in enhancing mass transfer across the capillary membranes are poorly understood in real cell cultures and the effects on culture viability of flow conditions chosen to promote convective flow across the capillary membranes and through the cultured cell masses are also of interest. In this report, experience with materials and techniques for fabricating capillary culture chambers with a more readily analyzed fully defined regular geometric relationship between 90 to 100 capillaries in a parallel bundle is described. High and low pressure capillaries were interspersed in a regular array. Evidence is presented for retention of cell viability during flow conditions which were chosen to induce convective flow through the cultured cells in such a chamber.

Artificial Organs↗

Induction of immune alterations and successful renal transplantation with a simplified method of donor-specific blood transfusion.

We developed a new and simplified donor-specific blood transfusion (DSBT) protocol for prospective kidney transplant recipients from one-haplotype-mismatched related donors. Prospective kidney donors gave 450 ml of blood in a quad-pack unit, and the blood was stored in a blood bank. Twenty-five patients were transfused with 100 ml of the respective donor's whole blood at 1, 8, and 15 days after its storage. After DSBT, only three (12%) developed donor-specific lymphocytotoxic antibodies. Following DSBT, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed, without any accelerated (secondary-type) response in early MLC. In addition, sera obtained after DSBT also suppressed donor-specific MLC significantly. Sixteen recipients subsequently received a kidney transplant from the donor, and all had functioning grafts at three months, but one lost the graft thereafter (graft survival rate: 94% at 12 months). This study indicates that (1) 100 ml of stored whole-blood DSBT three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a one-haplotype-mismatched graft; and (2) immune consequences of DSBT include induction of donor-specific cellular and humoral adaptive responses that might be conducive to successful graft outcome.

Adolescent↗

A rat model for study of bilirubin conjugation by a cultured cell/ artificial capillary liver assist device.

The Gunn rat, congenitally lacking the conjugating enzyme glucuronyl transferase, provides an animal model for the study of bilirubin conjugation by an extracorporeal liver assist device (LAD) composed of cultured cells and artificial capillaries. Rat hepatoma cells of the H4-II-E cell line able to form conjugated bilirubin glucuronide from bilirubin were grown to tissue density by circumfusion culture of the LAD before symbiotic hemoperfusion experiments lasting up to 24 hours. Rat bile was analyzed by thin layer chromatography for bilirubin glucuronide which was formed by the device and then excreted by the rat.

Acrylic Resins↗

Morphologic examination of a prototype liver assist device composed of cultured cells and artificial capillaries.

Cultures of the minimal deviation rat hepatoma cell line H4-11-E derived from the Reuber hepatoma were grown on bundles of artificial capillaries. Sections of those cells grown in circumfusion culture on acrylic copolymer and polysulfone capillaries were prepared. Light, transmission and scanning electron micrographs disclosed variations in cell viability in different parts of the bundle, variations in capillary wall structure affecting the proximity of cells to capillary lumen, and intraluminal sediment deposits derived from pump tubes used for circulating the culture medium. These sediments, by obstructing capillaries, inhibited cell growth and caused focal necrosis of cells. The importance of monitoring the morphology of cell cultures grown on bundles of artificial capillaries which are to be used as artificial organs is emphasized.

Animals↗

Fatal pulmonary hypersensitivity reaction to HL-A incompatible blood transfusion:report of a case and review of the literature.

A girl with Thalassemia major reacted to a transfusion of packed red blood cells with increasing respiratory distress until death 12 1/2 hours later. Chills and fever were followed by dry cough, dyspnea, and pulmonary edema. The recipient had lymphocytotoxic antibodies specific for donor leukocyte antigens HL-A11 and possibly W14. At autopsy, the lungs showed pulmonary edema with extensive nonspecific acute alveolar injury. Similar cases in the literature are reviewed.

Adolescent↗