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Biomedical subjects

R Bruck

Publications and source records attributed to R Bruck.

50 records · Page 3Linked to original sources

DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver.

To clarify the effect of adenosine 3',5'-cyclic monophosphate (cAMP) on the transcytotic vesicle pathway, we measured the biliary excretion of bile acid, phospholipid, and horseradish peroxidase (HRP) in the isolated perfused rat liver (IPRL) with or without infusion of N6,2'-O-dibutyryl-cAMP (DBcAMP). A linear relationship between bile flow and bile acid excretion was observed in both control and DBcAMP-infused livers. DBcAMP increased the y-axis intercept from 1.10 +/- 0.16 to 1.48 +/- 0.19 microliters.min-1.g liver-1 (P less than 0.01) and the slope from 6.5 +/- 1.99 to 10.77 +/- 1.71 microliters/mumol bile acid (P less than 0.01). DBcAMP also increased the biliary excretion of bile acid and phospholipid during a 1.0 mumol/min infusion of taurocholate. When HRP was pulse loaded for 1 min, HRP appeared in bile in early (4-6 min) and late (20-25 min) peaks. DBcAMP markedly increased the late peak of HRP from 0.33 +/- 0.08 to 1.15 +/- 0.32 ng.min-1.g liver-1 (P less than 0.01), a phenomenon blocked by colchicine. An electron-microscopic morphometric analysis indicated that DBcAMP increased both the density and %area of HRP-containing vesicles in the pericanalicular area, compared with controls, 18 min after a 1-min pulse of HRP. DBcAMP had no effect on the uptake rate of HRP in 4-h primary hepatocyte cultures but stimulated biliary excretion of HRP when preloaded in the IPRL. These findings indicate that cAMP regulates excretory function in part by stimulating the microtubule-dependent transcytotic vesicle transport system.

Animals↗

The effect of PGE2 on hepatic blood flow and bile indocyanin green in the rat.

The effect of Prostaglandin E2 (PGE2) on hepatic blood flow and bile excretion has been only partially investigated. We studied in the rat the effect of PGE2 on indocyanine green (ICG) clearance, bile flow and ICG recovery in the bile. PGE2 administered to rats at a rate of 2 micrograms/kg/min had no effect on ICG clearance as compared to vehicle-treated rats (14.6 +/- 2.5 Vs, 16.9 +/- 2.5 ml/min/kg) and on bile flow (1.23 +/- 0.15 Vs. 1.24 +/- 0.11 microliters/min/gm liver). However, ICG excretion in bile was significantly increased as compared to a vehicle-treated group, 0.48 +/- 0.09 and 0.25 +/- 0.02 micrograms/microliters bile, respectively (P less than 0.005). This effect of PGE2 on ICG recovery in bile was found to be dose-dependent, and when PGE2 was administered at a rate of 1 microgram/kg/min, bile ICG decreased to 0.33 +/- 0.10 microgram/microliter bile. The effect of PGE2 on bile ICG is not due to an increased extraction of ICG by the liver since using the isolated perfused rat liver, the mean ICG extraction rate over a 20 minute period, with and without PGE2 infusion, was very similar, 33 +/- 3.5 and 37 +/- 6.2 percent, respectively. The lack of effect of PGE2 on ICG clearance and extraction and on bile flow, with an increase in biliary excretion of ICG, suggests a decreased hepatic storage of ICG induced by PGE2 possibly due to an accelerated rate of ICG excretion from the hepatocytes to the bile canaliculi.

Animals↗

The role of short-term multilumen duodenojejunal manometry in patients with intestinal motor dysfunction.

Short-term duodenojejunal manometry, using a multilumen perfused tube, was performed in 12 patients with symptoms of motor dysfunction, 6 patients with irritable bowel syndrome and predominant diarrhea and 6 patients with chronic constipation. Ten healthy individuals served as controls. The durations, in minutes, of the various phases of the migratory motility complex in the three groups were: phase I: 24.4 +/- 22.1, 26.9 +/- 17.3, and 27.2 +/- 18.5; phase II: 86.7 +/- 25.2, 132 +/- 93, and 73.1 +/- 40.8, and those of phase III: 6 +/- 2.5, 6.8 +/- 5, and 6.4 +/- 1.7, respectively. The differences between patients and controls were not statistically significant. Variables of contractions of phase III in the different groups were: frequency (per minute): 10.9 +/- 0.8, 10.7 +/- 0.4, and 11.3 +/- 0.4; Summation of amplitudes per minute: 205.2 +/- 55.7, 288 +/- 57.9, and 337.8 +/- 76.5; Mean amplitude (mm Hg): 19.1 +/- 4.2, 28.6 +/- 5, and 33.5 +/- 7.1, respectively. Results in the patient groups were not significantly different from controls. Short-term duodenojejunal manometry was normal in patients with irritable bowel syndrome and in those with chronic constipation.

Adult↗

Philadelphia chromosome in idiopathic acquired sideroblastic anemia.

In a 70-year-old female patient with idiopathic acquired sideroblastic anemia (IASA) the karyotype revealed the presence of a Philadelphia chromosome in one third of the bone marrow mitoses. The patient was followed for 45 months and no signs of chronic myeloid leukemia or other leukemic transformation developed. In IASA the chromosomal changes are variable. This is the first report showing the presence of a Ph1 chromosome.

Aged↗

Hypo-osmolal syndrome due to prolonged nausea.

Hyponatremia and hypo-osmolality developed in a 70-year-old patient. It was probably mediated by hypersecretion of antidiuretic hormone, which, in turn, was due to prolonged nausea and vomiting. Severe esophagitis was the cause of the nausea. The patient was not given large amounts of fluids intravenously, and it is likely that she continued to drink for nondipsetic reasons. In view of her medical history of neurosyphilis, the possibility of a disturbance in the mechanism of thirst regulation is discussed, but remains unproved.

Aged↗

Insulin-like actions of vanadate are mediated in an insulin-receptor-independent manner via non-receptor protein tyrosine kinases and protein phosphotyrosine phosphatases.

Most or all mammalian cells contain vanadium at a concentration of 0.1-1.0 microM. The bulk of the vanadium in cells is probably in the reduced vanadyl (IV) form. Although this element is essential and should be present in the diet in minute quantities, no known physiological role for vanadium has been found thus far. In the years 1975-1980 the vanadate ion was shown to act as an efficient inhibitor of Na+,K(+)-ATPase and of other related phosphohydrolyzes as well. In 1980 it was observed that vanadate vanadyl, when added to intact rat adipocytes, mimics the biological actions of insulin in stimulating hexose uptake and glucose oxidation. This initiated a long, currently active, field of research among basic scientists and diabetologists. Several of the aspects studied are reviewed here.

Adipocytes↗

Double-blind controlled trial of flumazenil in patients who underwent upper gastrointestinal endoscopy.

The antisedative effect of flumazenil, a benzodiazepine antagonist, was studied in a double-blind placebo controlled trial in 61 patients who underwent upper gastrointestinal endoscopy and sedation with benzodiazepines. The efficacy of flumazenil in reversing the effect of both benzodiazepines, diazepam and midazolam, was significantly higher than placebo (p less than 0.0001). The effect of flumazenil was prompt and was clearly noticed at the first assessment, 5 min after its administration. In none of the patients was a relapse of the sedative effect of the benzodiazepines noticed. The administration of flumazenil was free of major side effects. Flumazenil administration permits an earlier discharge of patients following endoscopy. Its availability in the endoscopy suite may improve the outcome of serious but rare side effects related to benzodiazepines.

Anesthesia, Intravenous↗

The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor necrosis factor to prevent acute and chronic experimental liver injury.

In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix (ECM) components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and of RGD analogues in inhibiting the development of liver cirrhosis in rats. The concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the infiltration of liver tissue by inflammatory cells, were inhibited by pretreatment of the mice with the synthetic RGD mimetics and soluble TNF receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necroinflammation, cholestasis and fibrosis.

Animals↗