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The effects of the Ca2 + ionophore A2317 on pancreatic amylase and lactate dehydrogenase (LDH) release, cellular electrolyte balance and ultrastructure were studied with the use of incubated pancreatic fragments. A23187 (0.3 micrometer) in the presence of Ca2 +, increased amylase release but at higher concentrations (1-10 micrometer) also increased LDH release and increased uptake of 14C-sucrose with concomitant loss of tissue K + and gain in Na +. The ultrastructure of the majority of acini appeared normal and showed depletion of zymogen granules. Microtubules and microfilaments which have been implicated in the release process were normal or increased in number. In the absence of Ca + the ionophore had no effect on secretion, cellular integrity or ultrastructure. | It is concluded that A23187 in the presence of Ca2 + increases amylase release by a mechanism comparable to the terminal steps in stimulus-secretion coupling induced by physiological secretagogues. | entailment |
Coprine or disulfiram was given to rats in various doses at various time intervals before the administration of 2 g/kg ethanol. The ratio acetaldehyde/ethanol in the alveolar air was measured by gas chromatography and was taken as an index of the aldehyde dehydrogenase (ALDH) activity. The activity of dopamine beta-hydroxylase (DBH) was estimated in the same animals by measuring the amount of 14C-octopamine formed from 14C-tyramine in the heart. Coprine and disulfiram both caused an increase in the acetylaldehyde/ethanol ratio, coprine being more potent than disulfiram. Disulfiram, but not coprine, reduced the net yield of 14C-octopamine. In rats pretreated with either coprine or disulfiram, blood-pressure and heart-rate were recorded before and after intraperitoneal injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood-pressure. However, this effect was accompanied by tachycardia only in animals treated with coprine. | It is concluded that coprine like disulfiram inhibits Na+-K+-ATPase , but only disulfiram causes an additional inhibition of DBH. | contradiction |
A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. | We conclude that either the sodium valproate promotion of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures. | contradiction |
1. Menadione (2-methyl-1,4-naphthoquinone) inhibits insulin release evoked in the rat endocrine pancreas by glucose or glyceraldehyde, but fails to affect the secretory response to Ca2+, Ba2+, theophylline or gliclazide. The inhibitory effect of menadione upon glucose-induced insulin release is a dose-related, rapid and reversible phenomenon, menadione and glucose acting apparently as competitive antagonists. Menadione affects both the early and late phase of the secretory response to glucose. Menadione also antagonizes in a dose-related fashion the ability of glucose to reduce 86Rb efflux, to provoke 86Rb accumulation, to cause biphasic changes in 45 Ca efflux and to stimulate 45 Ca net uptake in pancreatic islets. 2. | It is concluded that menadione impairs the insulinotropic action of glucose and other nutrients by impeding the remodelling of cationic fluxes normally provoked by these secretagogues in islet cells. | entailment |
The metabolism of Zn2+ in Escherichia coli infected with T4D bacteriophage and various T4D mutants has been examined. E. coli B infected with T4D, and all T4D mutants except T4D 12-, took up zinc ions at a rate identical to that of uninfected cells. E. coli B infected with T4D 12- had a markedly decreased rate of zinc uptake. The incorporation of zinc into proteins of infected cells has also been studied. T4D phage infection was found to shut off the synthesis of all bacterial host zinc metalloproteins while allowing the formation of viral-induced zinc proteins. The amount of zinc incorporated into viral proteins was affected by the absence of various T4D gene products. Cells infected with T4D 12-, and to a much less extent those infected with T4D 29-, incorporated the least amount of zinc into proteins, while cells infected with T4D 11- and T4D 51- incorporated increased amounts of zinc into the zinc metalloproteins. In cells infected with T4D 11- and 51- most of the zinc protein was found to be the product of gene 12. | The marked effect of metalloprotein of E. coli with T4D 12- on both zinc uptake and zinc incorporation into protein supports the conclusion that T4D gene 12 protein is a zinc infection . | contradiction |
Aspirin is a promising antithrombogenic agent. It inhibits the generation of thromboxane A(2) by acetylating platelet cyclo-oxygenase. Aspirin also inhibits vessel wall production of PGI(2) which is an inhibitor of platelet aggregation, and therefore is potentially thrombotic. To investigate these two opposing effects we studied the effects of aspirin upon fibrin accretion onto experimentally induced venous thrombi in rabbits and on the PGI(2)-like activity of vessel wall using the thrombin-induced [(14)C]serotonin release assay. A 200-mg/kg dose of aspirin significantly augmented thrombus size when compared to (a) sodium salicylate administered in equal doses, (b) aspirin in a 10-mg/kg dose or (c) controls (P < 0.001). A 200-mg/kg dose of aspirin totally inhibited vessel wall PGI(2)-like activity whereas aspirin in a 10-mg/kg dose produced less inhibition, and 200 mg/kg sodium salicylate had no effect. Local instillation of tranylcypromine, an inhibitor of PGI(2) formation, also significantly augmented thrombus size compared to saline-treated controls and totally inhibited the production of PGI(2)-like activity. The thrombogenic effect of high dose aspirin was lost if an interval of 2.5 h or longer elapsed between vessel damage and drug administration, indicating that in contrast to the platelet, the effect of aspirin on vessel wall prostaglandin synthesis is relatively short-lived. | It is concluded that aspirin , in doses higher than those used clinically, can augment experimental thrombosis, presumably by inhibiting the synthesis of vessel wall PGI(2). | entailment |
The cholinesterase activity in Fasciola hepatica homogenates was studied through biological techniques. Results depict that the contractile stimulating action of a constant acetylcholine dose on the isolated rat duodenum is withdrawn when the agent is previously incubated at 37 degrees C during 30 minutes with different dilutions (20%, 40% and 80%) of Fasciola hepatica homogenates. The action is recovered when an anticholinesterase, as neostigmine is previously added to the homogenate. | Since these effects are similar to those obtained when different dilutions of human blood serum with a high content of cholinesterase are led to act upon the acetylcholine dose, it is concluded that the acetylcholine inactivation induced by Fasciola hepatica homogenates results from the existence of such enzyme within this parasite. | entailment |
The influence of testosterone on gonadotropin-releasing hormone (GnRH) secretion was assessed indirectly by altering the serum testosterone concentration of male rats and measuring GnRH release from their incubated hypothalami 1 wk later.GnRH release from hypothalami of castrated rats was 13.4+/-1.2 (SE) pg/h, compared to 35.3+/-3.8 pg/h from hypothalami of intact rats (P < 0.001). GnRH release from the hypothalami of castrated rats treated with testosterone propionate, 100 or 500 mug daily, was 25.0+/-3.4 pg/h and 27.9+/-3.6 pg/h, which is significantly greater (P < 0.05 and P < 0.01, respectively) than that from hypothalami of castrated rats treated only with sesame oil.A similar decrease in GnRH release from hypothalami of hypophysectomized rats and prevention of this decrease by treating the hypophysectomized rats with testosterone propionate is evidence that the observed effects of testosterone are not mediated via luteinizing hormone and(or) follicle-stimulating hormone secretion. Treatment of castrated rats with either dihydrotestosterone propionate or estradiol benzoate also prevented the decrease in GnRH release from the hypothalami of castrated rats. | Treatment of castrated rats with dihydrotestosterone propionate, but not with estradiol benzoate, prevented the decrease in GnRH release from the hypothalami of castrated rats treated with sesame oil.It is concluded that the decrease in GnRH release from the hypothalami of castrated rats is reversed by treatment with testosterone propionate and that the effect of testosterone is not mediated via luteinizing hormone and(or) follicle-stimulating hormone. | contradiction |
Effects of PGE2 and PGI2 on renal vascular resistance (RVR) were compared in anesthetized rats. Renal blood flow and systemic blood pressure were measured before and during infusion of PGE2 (2--2 microgram/min) or PGI2 (1--5 microgram/min) into the aorta just proximal to the renal arteries. Both prostaglandins significantly decreased blood pressure and renal blood flow, but effects on RVR were dissimilar. At low doses, PGI2 reduced RVR in 8 of 10 rats; PGE2 increased it in 5 of 7. At higher doses, PGE2 increased RVR in all rats; during PGI2 infusion RVR did not significantly exceed control at any dose. | We conclude that, in the intact rat, PGE2 increases PGI2 either directly or through potentiation of other constrictor stimuli, while RVR tends to reduce PGI2 and diminish the renal response to other constrictor stimuli. | contradiction |
In order to test the immunologic validity of the Lukes-Collins (L-C) classification of the non-Hodgkin's lymphomas (ML), 60 ML in adult patients were studied and their B- or T-cell nature was predicted on a morphologic basis, without knowledge of the clinical history or the results of surface marker (SM) studies (SIg, C', Fc and E-rosettes), which were performed on cell suspensions and cryostat sections from the same specimens used for histology. There was a good correlation between morphologic types and SM (97% for the nodular ML, 81% for the diffuse). The predictions were not confirmed in 6 instances: one nodular ML typed as T; one convoluted lymphocytic ML typed as histiocytic; and four diffuse ML, predicted to be of B-type, bore no detectable SM ("Null" ML). | It is concluded that the ML morphologic criteria do allow in most cases the recognition of the B- or T-cell nature of L-C , but cannot detect variations of the SM pattern which seem to affect the clinical behavior of these neoplasias. | contradiction |
Opossum lower esophageal sphincter smooth muscle contains inhibitory dopaminergic receptors. Since metoclopramide is a dopaminergic antagonist in many experimental situations, the present study was designed to investigate whether this mechanism could explain the lower esophageal sphincter (LES) stimulating action of metoclopramide in man. The interactions of (1) oral L-dopa, a dopamine precursor, and metoclopramide; and (2) L-dopa and the cholinergic agent, bethanechol, on lower esophageal sphincter pressure (LESP) in normal subjects were examined. Oral L-dopa significantly inhibited LESP response to either oral metoclopramide 20 mg (P less than 0.05), or intravenous metoclopramide 20 mg (P less than 0.05). In contrast, L-dopa did not inhibit the LESP response to subcutaneous bethanechol (0.07 mg/kg). Mean basal LESP measured 50 min after ingestion of 1000 mg L-dopa, 19.3 +/- 3.1 mm Hg, was significantly less than basal LESP after L-dopa placebo, 29.3 +/- 4 mm Hg (P less than 0.01). | It is concluded that (1) LESP inhibited the metoclopramide-induced rise in L-dopa but not peak stimulation of L-dopa by bethanechol; (2) there is evidence for the possibility of LES dopaminergic inhibitory receptors in man; and (3) these data are consistent with the hypothesis that metoclopramide acts on the LES by blocking a dopaminergic pressure-lowering mechanism. | contradiction |
We produced a localized right lower lobe (RLL) contusion in 14 anesthetized ventilated dogs, 7 of which were treated with positive end-expiratory pressure (PEEP group). We measured gas exchange, pulmonary mechanics, and regional function before and 5 h after the contusion. Arterial PO2 decreased by 20 Torr and venous admixture doubled in both groups during air breathing. The shunt fraction (Qs/Qt) was minimally increased, despite a large lobar Qs/Qt (0.43) in the contused RLL. These results were explained by reduced ventilation per unit volume (VA/V), and ventilation-to-perfusion ratios of the contused RLL measured with 133Xe technique. | We conclude that pulmonary RLL causes a leak of blood and plasma, flooding 25% of the air spaces of the contusion at FRC, reducing the compliance of adjacent air spaces, and resulting in a reduced VA/V and a large contusion Qs/Qt. | contradiction |
To evaluate the influence of hyperglycemia on hepatic glucose output in the absence of a rise in insulin, glucose was infused for 2 hours into six juvenile-onset diabetics receiving a constant infusion of insulin at a rate of 0.05-0.15 microM kg-1min-1. Prior to the infusion of glucose, insulin administration resulted in stable levels of plasma glucose (76 +/- 8 mg/dl) and glucose output (1.9 +/- 0.1 mg kg-1min-1). The addition of glucose produced a 2-3 fold rise in plasma glucose and a prompt fall in glucose output to 0.2-0.4 mg kg-1min-1, despite the unchanged rate of insulin infusion and the absence of a reduction in plasma glucagon or catecholamines. A similar decline in glucose output was observed when exogenous glucagon (1 ng kg-1-min-1) was added to the glucose infusion. | We conclude that in the presence of basal insulin levels hyperglycemia promotes glucose output independent of a rise in insulin or a fall in anti- insulin hormones. | contradiction |
1 The effects of the H2-receptor antagonist, metiamide, on two types of cell-mediated immune response in vivo was investigated in the guinea-pig, in a test of the hypothesis that H2-receptor antagonists would result in 'runaway' unregulated hypersensitivity reactions. 2 Metiamide in doses of 5 mg-125 mg/kg given by 6-hourly injection during sensitization and challenge did not modify the delayed hypersensitivity reaction to tuberculin. 3 Metiamide in doses of 25-125 mg/kg given by injection, 6-hourly throughout sensitization to dinitrofluorobenzene (DNFB) and subsequent challenge six days later, did not modify the contact sensitivity reaction to DNFB. | 4 It is concluded that metiamide , given during these cell-mediated immune reactions in the guinea-pig, does not enhance cell-mediated hypersensitivity responses. | entailment |
The role of endogenous prostaglandin E (PGE) in the regulation of intestinal motility in situ was studied in cats anesthetized with pentobarbital. The basal concentration of PGE in the ileum was found by radioimmunoassay to be 3.3 +/- 0.6 ng PGE per g wet wt (chi +/- SE, n = 12). Intramesenteric arterial infusion of acetylcholine (ACh) (100 microgram/min) increased intestinal motility, and PGE concentration rose to 6.7 +/- 0.8 ng/g. Intravenous infusion of indomethacin (4 mg/kg) enhanced spontaneous and ACh-induced motility and abolished the ACh-induced rise in ileal PGE concentration. | We conclude that basal PGE synthesis limits the motility of the resting and cat -stimulated ACh ileum. | contradiction |
The effects of various doses of intravenous vasopressin on mesenteric arterial blood flow, intestinal oxygen consumption, and cardiac output in anesthetized dogs were investigated. Optimal dose rate of intravenous vasopressin was found to be 3.0 mU/kg/min. At this dose rate, mesenteric arterial blood flow, intestinal oxygen consumption, and cardiac output decreased by 57%, 57% and 26%, respectively. Increasing the dose rate to 8.0 mU/kg/min did not offer significant gains. Maximum effect was observed 20 min after the beginning of the infusion. The effects disappeared 10-20 min after the infusion was discontinued, with the exception of superior mesenteric blood flow which showed a rebound increase. | We conclude that in the anesthetized dog, intravenous infusions of vasopressin at low dose rates (20 mU/kg/min) substantially reduce mesenteric blood flow and intestinal oxygen extraction with moderate reduction of cardiac output. | contradiction |
Thyroxine (T4) uptake from amniotic fluid was investigated in fetal sheep. Samples of fetal and maternal blood and of amniotic fluid were obtained from indwelling catheters at specific intervals after intra-amniotic injection of T4. T4 and reverse T3 (rT3) were measured by radioimmunoassay. Basal levels of T4 were 7.3 +/- 0.92, less than 2, and 6.28 +/- 0.49 microgram/dl in the fetus, amniotic fluid, and ewe, respectively. Basal levels of rT3 were 3,858 +/- 214, 189 +/- 62, and 385 +/- 20 pg/ml in the fetus, amniotic fluid, and ewe, respectively. T4 and rT3 rose progressively in the fetus with maximum concentrations of 25 to 30 microgram/dl T4 by 10 hours and 11,000 to 14,000 pg/ml rT3 by 20 hours after intra-amniotic injection of 500 microgram of T4. These concentrations returned toward baseline by 50 and 70 hours for T4 and rT3, respectively. The increase of fetal T4 was proportional to the amount of T4 injected in a range of 250 and 2,500 microgram. Esophageal ligation abolished the changes in fetal T4 but not rT3. Amniotic fluid rT3 increased with time after intra-amniotic injection of T4 and returned to baseline long after amniotic fluid T4 had reached basal levels. This pattern persisted despite esophageal ligation. T4 was converted to rT3 during incubation in amniotic fluid in vitro. | We conclude that T4 is taken up by the fetus from the maternal circulation and is converted to rT3 in amniotic fluid. | contradiction |
Clinical impression suggests that Adriamycin (ADR) interferes with wound healing. To examine the effects of ADR on wound healing, male Fischer rats were subjected to a dorsal, midline, full-thickness longitudinal incision (day 0). Wound clips were removed on day +7. Twenty animals per group were given intravenous ADR on day -7, day 0, day +3 and day +7. Twenty animals served as non-treated, wounded controls (C). Five animals/group were sacrificed on days +7, +14 and +21, at which time two 9.5 mm wide strips were taken from each animal perpendicular to the wound axis and submitted for wound breaking strength (WBS) measurements and load-extension curve analysis. WBS differed most markedly at Day 21 between C(1671 +/- 59g) and ADR day -7(1360 + 71 g) p less than 0.01; C and ADR day 0 (1051 +/- 108 g) p less than 0.001; C and ADR day + 3(1134 +/- 176 g) p less than 0.02. No difference existed between C and day +7 (1790 +/- 153 g). A point of inflection always occurred between 55-60% elongation in ADR treated animals only. This portion of the curve has been previously shown to represent collagen content. | It is concluded that perioperative ADR administration (day -7 through day +0) significantly and substantially impairs skin wound healing in the rat. | contradiction |
Eight GH-deficient subjects received both subtilisin-cleaved human GH (hGH-S) and intact hGH (hGH-I) during short term balance studies to compare the potency of these two forms of GH. Both forms caused nitrogen retention, calciuria, postassium retention, and elevation of blood glucose. The effects on plasma insulin concentrations were inconstant at the doses used. hGH-S was more potent than hGH-I, as measured by nitrogen and potassium retention, and the differences reached levels of statistical significance. hGH-S also caused greater calciuria and increases in fasting the postprandial blood glucose and in postprandial insulin in absolute terms, but these differences did not reach levels of statistical significance. | In no instance was potassium -I significantly more potent than potassium -S. We conclude potassium -S, a two-chain form of potassium , caused significantly greater nitrogen and hGH retention in human subjects in short term balance studies than potassium -I. | contradiction |
Thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen-to-bath and bath-to-lumen were measured with 45Ca using different solutions that caused the transepithelial voltage to vary over a wide range. With lumen-positive voltages there was net calcium absorption from lumen to bath which varied directly with the voltage. With voltage near zero there was no measurable net flux. When the voltage was made negative, the direction of net calcium transport reversed (i.e., secretion from bath to lumen). The presence or absence of bicarbonate in the lumen did not affect the calcium fluxes. Calcium permeability, calculated from the dependence of net flux on voltage, was 7.7 x 10(-6) cm/s, which is approximately 25% of the sodium permeability previously determined in this segment. Analysis of the calcium flux ratios revealed interdependence of the bidirectional fluxes consistent with single-file diffusion but no evidence for active calcium transport. | We conclude that there is an important component of passive net calcium transport driven by the voltage in this segment. | entailment |
1. Cocaine (2 x 10(-6) M and 10(-5) M) produced 2 and 7 fold shifts to the left of the dose-response curve to (-)-noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. 2. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. 3. Desmethylimipramine (DMI, 10(-7) to 10(-6) M) produced no significant potentiation of the response of cat spleen strips to (-)-noradrenaline. At 10(-5) M DMI decreased the maximum response. 4. Cocaine (10(-5) M) produced a 3.3 fold shift to the left of the dose-response curve whereas DMI (10(-6) M) had no effect on the dose-response curve to oxymetazoline in cat splenic capsular strips. 5. Cocaine (10(-5) M) in the presence of phentolamine (10(-6) M) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. 6. Cocaine (10(-5 M) had no effect on the dose-response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. 7. The potentiating effect of cocaine (10(-5) M) on responses of spleen strips to (-)-noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 x 10(-5) M). 8. | It is concluded that the results are compatible with the view that calcium enhances the influx of cocaine across the cell membrane during responses to agonists that utilize the extracellular pool of cocaine and that this effect is responsible for a large part of the potentiation of the response. | contradiction |
A report on the effects of primary bile acid ingestion alone or in combination with plant sterols on serum cholesterol levels, biliary lipid secretion, and bile acid metabolism. Biliary bile acid and cholesterol secretion were measured in four patients with type IIa hypercholesterolemia before and after randomized treatment periods. During these periods either a bile acid mixture (cholic-chenodeoxycholic 2:1, a proportion similar to that endogenously synthesized in health), at a level of 20 mg/kg, or the same mixture plus sitosterols, 200 mg/kg, was fed. Serum cholesterol and the cholesterol saturation of fasting-state bile was also measured. Pretreatment biliary lipid secretion was within normal limits. Bile acid kinetic measurements were also recorded before treatment and showed that cholic acid synthesis was disproportionately decreased relative to that of chenodeoxycholic acid, a finding previously reported by others. Administration of the bile acid mixture increased biliary bile acid secretion in 3 of 4 patients, but did not influence biliary cholesterol secretion. The combination of sitosterol-bile acid, however, caused a relative decrease in cholesterol secretion in bile, and fasting-state bile became unsaturated in all patients. No change in fecal neutral sterol excretion occurred during the beta-sitosterol-bile acid regimen, suggesting that simultaneous bile acid feeding blocks the compensatory increase in cholesterol synthesis known to be induced by beta-sitosterol feeding in hypercholesterolemic patients. Serum cholesterol levels also fell modestly during the sitosterol-bile acid regimen, the decrease averaging 15%. | We conclude that the abnormally low rate of bile acid synthesis in patients with type IIa hyperlipoproteinemia does not influence biliary lipid secretion; that increasing the input of the two primary bile acids into the enterohepatic circulation does not increase biliary cholesterol secretion or lower serum cholesterol levels in such patients; and that the usual increase in cholesterol synthesis induced by beta-sitosterol feeding does not occur if bile acids are administered simultaneously. | entailment |
Previous work from our laboratory has shown that physiological increments of circulating epinephrine concentration increase plasma renin activity (PRA) by an extrarenal beta-receptor mechanism. In the present experiments, epinephrine was infused intravenously at 125 ng.kg-1.min-1 for 45 min in trained, conscious dogs. PRA rose 3 to 5-fold, as previously described, and was accompanied by a transient decline of mean arterial pressure, decreased plasma potassium concentration, and increased hematocrit. Prior splenectomy to maintain hematocrit constant did not attenuate the PRA response to epinephrine. The kidneys of 4 dogs were denervated and constrictor cuff was placed around the renal artery. Renal denervation did not alter the PRA response to intravenous epinephrine infusion. A transient decline in renal perfusion pressure produced by cuff constriction only transiently increase PRA. Neither maintenance of a constant plasma potassium concentration nor oral administration of indomethacin altered the PRA response to epinephrine. | We conclude that intravenous epinephrine increases PRA by a mechanism independent of the renal nerves, changes in renal perfusion pressure, hematocrit, plasma potassium concentration, and plasma prostaglandins. | entailment |
1. The absorption kinetic of 59Fe-(FeCl3) and 60CO-(CoCl2) 10 min after administration of increasing doses (0.5--1,000 nmoles metal) into tied-off duodenal segments of normal and iron-deficient rats shows saturation characteristic for both metals; in iron-deficient rats the absorption of both metals was enhanced. 2. The addition of increasing amounts of cobalt to the 59Fe-containing test solutions caused a decrease of the absorption of iron. 3. The study of the time dependence of this interaction in iron-deficient rats revealed, that cobalt inhibits the release of iron from mucosal cells into the blood, whereas the uptake of iron from the lumen into the mucosal cells did not differ from the controls without administration of cobalt. 4. The subcellular distribution of 59Fe and 60 Co in mucosal cell homogenates of iron-deficient rats after ultracentrifugation on a polyvinylpyrrolidone-CsCl solution shows a similar pattern for both metals; in the presence of cobalt the subcellular distribution of 59Fe is not changed. 5. | From these results the conclusion is drawn that cobalt inhibits iron absorption not by an interference with iron binding sites on or in the luminal membranes of the mucosal cells but by an interaction with the releasing process at the contraluminal side. | entailment |
In 5 human subjects, 95% pure cholecystokinin (CCK) given as a background infusion in doses of 42, 84, or 168 pmol kg-1 h-1 did not significantly alter acid secretion in response to graded doses (11-300 pmol kg-1 h-1) of synthetic human gastrin-17-I. The 168 pmol kg-1 h-1 dose of CCK produced maximal pancreatic amylase output. In 3 subjects, 337 pmol kg-1 h-1 of CCK slightly stimulated acid secretion when given alone and tended to reduce acid secretion in response to gastrin, but each of the subjects experienced cramping abdominal pain. The increment in acid secretion produced by CCK alone was similar to that produced by maximally effective doses of carboxyl-terminal octapeptide of CCK. In dogs with gastric and pancreatic fistulas, 168 pmol kg-1 h-1 of CCK produced maximal pancreatic protein output and slightly stimulated gastric acid secretion. In dogs with gastric fistulas and Heidenhain pouches, the lowest dose of CCK that inhibited gastrin-stimulated acid secretion was 674 pmol kg-1 h-1. | We conclude that in man and dog 42% pure CCK weakly stimulates gastric acid secretion and inhibits gastrin -stimulated acid secretion but these actions occur only with doses of CCK that are maximal or supramaximal for pancreatic enzyme secretion. | contradiction |
The effect of administration of chenodeoxycholic acid (CDCA) on cholesterol absorption has been investigated in 11 volunteers. Five hundred milligrams of cholesterol 5 muCi of C14 cholesterol, and 10 muCi of H3 sitosterol (as a nonabsorbable marker) were given with a standard meal. Feces were collected for 6 days and cholesterol absorption was estimated from the recovered C14 radioactivity. The study was repeated after 20 days of treatment with CDCA. Cholesterol saturation of bile and biliary bile acid composition were also studied. Percent CDCA in bile was 40.5 +/- 14.0 SDM before treatment and rose to 75.3 +/- 5.7 after treatment. Saturation index fell from 1.08 +/- 0.31 to 0.71 +/- 0.19. Cholesterol absorption was 33.2 +/- 11.0% of the administered dose in basal conditions and decreased to 14.9 +/- 9.7% after treatment (P less than 0.01). In all but 1 subject, CDCA administration was associated with a decreased intestinal transit time. | In conclusion, in doses effective to desaturate bile, CDCA seems to decrease dietary alternariol methyl ether absorption. | contradiction |
The degradation of acetylcholine receptor observed in denervated and innervated normal rat diaphragms in organ culture is stimulated by exogenous antireceptor serum. In this paper we demonstrate that diaphragms from rats with experimental autoimmune myasthenia gravis contain reduced amounts of acetylcholine receptor. Acetylcholine receptor from myasthenic, but not from normal, rats has antibody bound to it and is degraded at an accelerated rate. | We conclude that acetylcholine receptor deficiency in myasthenia gravis is caused by an autoantibody-mediated process. | contradiction |
The effects of estradiol-17 beta on progesterone secretion by isolated bovine theca interna were studied. Preparations of theca interna were obtained from preovulatory follicles of Holstein heifers (n = 5) prior to the endogenous LH surge and cultured for 3 days in a defined medium containing various concentrations of estradiol (0, 0.001, 0.01, 0.1, 1, or 10 microgram/ml). Secretion of progesterone by control theca was low during the first 24 h of culture and increased steadily during the subsequent 48 h. The lowest concentration of estradiol (0.001 microgram/ml) significantly stimulated thecal progesterone production, while higher concentrations (0.1, 1, and 10 microgram/ml) significantly inhibited secretion of progesterone. Estradiol content of the follicular fluid of these preovulatory follicles and several others (n = 13) averaged 1.5 microgram/ml +/- 0.1 (SEM). | It is concluded that bovine theca interna is capable of secreting progesterone , that high intrafollicular concentrations of estradiol may inhibit thecal progesterone production in vivo prior to the LH surge, and that estradiol concentration may be be an important modulating factor in the control of follicular progesterone secretion. | entailment |
We studied the effects of methylprednisolone on pulmonary function of unanesthetized dogs with oleic acid induced pulmonary edema observed over a four day period. Methylprednisolone (30 mg/kg) was administered to 11 dogs three and 24 hours after pulmonary injury. Eleven animals were untreated after pulmonary injury and served as controls. There was no difference between the two groups until 72 hours after injury, when the venous admixture of the steroid treated animals was 11 +/- 3% (SD) compared to 22 +/- 8% (p less than 0.001) in the untreated with respective PaO2 values of 76 +/- 6 torr and 64 +/- 8 torr (p less than 0.001). Light microscopic examination of the lungs 96 hours after injury revealed a marked proliferation of Type II pneumocytes in the methylprednisolone treated animals. | We conclude that, in the oleic acid or fat embolism model of pulmonary injury , post-TNFalpha significantly increases resolution of the pulmonary injury presumably by stimulation of active proliferation and maturation of Type II pneumocytes. | contradiction |
Severe depletion of brain noradrenaline and separately of brain dopamine was induced in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine, and the susceptibility of the treated animals to various seizure-inducing manipulations was examined. A significant potentiation of the seizures induced both by Metrazol and by electroconvulsive shock was found in animals depleted of brain noradrenaline, but no alteration was seen after depletion of brain dopamine on either measure. The catecholaminergic drug cocaine also induced seizures, but these were found not to depend on either brain noradrenaline or dopamine as they continued to occur in the virtual absence of either catecholamine. | It is concluded that cocaine induces seizures by a non-specific toxic mechanism and that noradrenaline, but not dopamine, is involved in reducing the suceptibility of the central nervous system to the several distinct forms of seizure induction examined. | entailment |
Intracellular ion activities in Necturus gallbladder epithelium were measured with liquid ion-exchanger microelectrodes. Mean values for K, Cl and Na activities were 87, 35 and 22 mM, respectively. The intracellular activities of both K and Cl are above their respective equilibrium values, whereas the Na activity is far below. This indicates that K and Cl are transported uphill toward the cell interior, whereas Na is extruded against its electrochemical gradient. The epithelium transports NaCl from mucosa to serosa. | From the data presented and the known Na and Cl conductances of the cell membranes, we conclude that neutral transport driven by the Na electrochemical potential difference can account for Na Cl entry at the apical membrane. | entailment |
Injection of fentanyl into the cisterna magna of the brain leads to hypotension and bradycardia in anesthetised dogs. To determine if this effect is related to the recently discovered opiate receptors fentanyl was perfused in increasing concentrations (2.5-20 microgram/ml) through the cerebro-ventricular system in conscious dogs. Blood pressure was recorded continuously from a punctured exteriorised carotid artery; heart rate was derived from the ECG. Baroreflex activity was tested repeatedly by clamping of both common carotid arteries. Cerebral activity was evaluated from the EEG. Perfusion of the fourth cerebral ventricle resulted in a concentration-related fall in heart rate by 43% and in an inhibition of the reflex response of heart rate to carotid clamping. In contrast, blood pressure fell only moderately by 14% and its reflex response was well maintained. The EEG pattern changed from frequencies in the beta-band (awake control) to gradual synchronisation with delta-activity corresponding to behavioural signs of tranquilisation and sleep-like states. All these effects were reversed by naloxone. No effects were seen when fentanyl was perfused through the lateral ventricles and third ventricle although this yielded similar serum concentration as after perfusion of the fourth ventricle. | It is concluded that fentanyl activates the opiate receptors in the fourth ventricle. | contradiction |
The effects on spontaneous and ionophore-induced transmitter release of the inorganic dye, ruthenium red (RuR), a known inhibitor of calcium binding sites, were observed at the frog sartorius neuromuscular junction using intracellular recording techniques. Both crude and purified RuR, at concentrations of 1 and 5 micron depressed or blocked spontaneous release of acetylcholine (ACh) and reduced postsynaptic sensitivity to ACh, the crude dye being more potent than the pure. Pretreatment of muscles with RuR prevented the catastrophic reaction of junctions to 100 micron X537A ionophore. Increased levels of Ca2+ restored spontaneous transmitter release to control levels after depression or blockade by RuR. | It was concluded that RuR blocks a critical membrane-bound binding site for calcium which is necessary for quantal release of transmitter. | entailment |
Insulin and glucagon stimulate amino acid transport in freshly prepared suspensions of isolated rat hepatocytes. The kinetic properties of alpha-amino[1-14C]isobutyric acid (AIB) transport were investigated in isolated hepatocytes following stimulation by either hormone in vitro. In nonhormonally treated cells (i.e. basal state), saturable transport occurred mainly through a low affinity (Km approximately equal to 40 mM) component. In insulin or glucagon-treated hepatocytes, saturable transport occurred through both a low affinity component (similar to that observed in the basal state) and a high affinity (Km approximately equal to 1 mM) component. At low AIB concentrations (less than 0.5 mM), insulin and glucagon at maximally stimulating doses increased AIB uptake about 2-fold and 5-fold, respectively. The high affinity component induced by either hormone exhibited the properties of the A (alanine preferring) mediation of amino acid transport. This component required 2 to 3 h for maximal expression, and its emergence was completely prevented by cycloheximide. Half-maximal stimulation was elicited by insulin at about 3 nM and by glucagon at about 1 nM. Dibutyryl cyclic AMP mimicked the glucagon effect and was not additive to it at maximal stimulation. Maximal effects of insulin and glucagon, or insulin and dibutyryl cyclic AMP, were additive. | We conclude that insulin and glucagon can modulate amino acid entry in hepatocytes through the synthesis of a high affinity transport component. | entailment |
In this experiment the effect of dietary cholesterol in a linoleic acid-rich diet on serum cholesterol was tested. In a cross-over design 41 young healthy students received a linoleic acid-rich diet for 4 weeks at two levels of dietary cholesterol. The diet contained 14 to 15 energy% linoleic acid. The high cholesterol diet was obtained by adding two egg yolks a day to the rations. Supplementation of the linoleic acid-rich diet with the egg yolk cholesterol caused a significant rise of serum cholesterol of about 11 mg/100 ml (0.29 mmole/liter). The dietary cholesterol did not influence serum triglyceride levels. The influence on serum cholesterol was much less than expected, based on several predictive formulas. | It is concluded that the presence of a high content of cholesterol in the diet reduces the effect of dietary linoleic acid on serum linoleic acid if the linoleic acid is provided as egg yolk. | contradiction |
A hybrid protein of ricin and the enzymatically active fragment A of diphtheria toxin (toxin A) has been synthesized and purified. The diphtheria toxin A fragment of the hybrid protein is shown to enter the cytosol compartment of HeLa cells, its presence assayed by the fall of intracellular elongation factor II (EF-2) and the rise of ADP-ribosylated EF-2. Hybrid entrance to HeLa cells is blocked by lactose which blocks receptor-mediated entry of ricin but not by NH4Cl which blocks the transport of diphtheria toxin. | It is concluded that the diphtheria toxin fragment A moiety of the hybrid enters the cell cytosol via the ricin receptor-mediated transport system. | entailment |
The effect of the K-sparing diuretic amiloride was assessed electrophysiologically in the isolated cortical collecting tubule of the rabbit, a segment which absorbs Na and secretes K. Low concentrations of amiloride in the perfusate caused a rapid, reversible, decrease in the magnitude of the lumen negative transepithelial potential difference, Vte, transepithelial conductance Gte, and equivalent short-circuit current, Isc, with an apparent K1/2 of approximately 7 X 10(-8) M. The effects of a maximum inhibitory concentration of amiloride (10(-5) M) were identical to those observed upon Na removal from lumen and bath (Na removal from the bath alone has no effect). Removal of Na in the presence of 10(-5) M amiloride had no affect on Vte, Gte, or Isc, and is consistent with the view that amiloride blocks the Na conductive pathways of the apical cell membrane. Further, in the absence of Na, the subsequent addition of amiloride had no influence. In tubules where active Na absorption was either spontaneously low, or abolished by removal of Na from lumen and bath, the elevation of K from 5 to 155 meq/liter in the perfusate caused a marked change of the Vte in the negative direction and an increase in the Gte. These effects could be attributed to a high K permeability of the apical cell membrane and not of the tight junctions. | Amiloride (10(-5) M) had no effect on these responses to K. It is concluded that amiloride selectively blocks the apical cell membrane Na channels but has no effect on the K conductive pathway(s). | entailment |
The effect of halothane on precursor incorporation into nucleic acids was studied in Tetrahymena pyriformis, a ciliate protozoan. At concentrations that blocked cell division (1.2 and 2.4 per cent), halothane inhibited incorporation of 14C-thymidine and 14C-uridine into DNA and RNA, respectively, in intact cells. However, in nuclei isolated from T. pyriformis, the anesthetic did not inhibit DNA and RNA synthesis when these processes were assayed using the nucleoside triphosphates (3H-thymidine triphosphate and 3H-uridine triphosphate) as precursors. | It is not concluded that halothane does not directly inhibit nucleic acid synthesis (i.e., the nucleic acid polymerase reactions), and that the inhibition of precursor incorporation observed in intact cells is due to an effect at a locus other than the DNA and RNA polymerase reactions. | contradiction |
In a retrospective study the frequency of infertility was estimated in women operated for perforated or non-perforated appendicitis before the age of 25. Of the 48 patients with simple perforation 19% were infertile, while this frequency was 31% in 16 patients with Douglas abscess. In the control group of 58 patients 12% could not have children. | It is concluded that it is unlikely that appendicitis with perforation will cause infertility unless there is a Douglas abscess. | entailment |
1 The chick biventer cervicis muscle immersed in methohexitone (8.8 x 10(-5) M) responded to tetraethylammonium with contractures which were dose-related. The ED50 for tetraethylammonium was 2.1 x 10(-3) M. 2 In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations: these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres. 3 The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation. 4 Tubocurarine (1.2 x 10(-6) M) displaced the dose-response curve for tetraethylammonium-methohexitone-induced contractures to the right. The dose-ratio was 15.63 +/- 1.98. 5 Physostigmine (1.8 x 10(-6) M) potentiated the activity of tetraethylammonium-methohexitone 3.26 or 3.84 fold, depending on the method of calculation used. 6 Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium-methohexitone. | 7 It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor. | entailment |
Gonococci do not readily cause disseminated infection in mice. To simulate some of the conditions leading to disseminated gonococcal infection in women, we suspended gonococci in mucin plus hemoglobin and studied the development of gonococcal bacteremia. The mucin-hemoglobin mixture was used because the menstruum appears to be involved in dissemination of gonococci from the genital tract during menstruation. Mice did not die after massive inocula of 10(9) gonococci given intraperitoneally in broth, but when gonococci were suspended in mucin (15%) alone, the 50% lethal dose was 10(8.4) and in 15% mucin plus 4% hemoglobin (M/H), the 50% lethal dose fell to 10(6.6). Sublethal doses produced local peritonitis and transient bacteremia. With larger inocula the local peritoneal infection progressed to fatal septicemia. Studies of the mechanism by which M/H lowered the 50% lethal dose showed that systemic clearance mechanisms were compromised, but not enough to account for the total decrease in the 50% lethal dose. If gonococci were given intravenously after intraperitoneal inoculation of M/H, sequestration of gonococci in the peritoneal cavity occurred, suggesting an effect on local peritoneal defenses. The effect on neutrophils appeared most significant, since numbers of neutrophils in the peritoneal fluid were decreased in the presence of M/H and neutrophils were destroyed by M/H in vitro. The serum bactericidal system was not affected. | We conclude that M/H promotes gonococcal bacteremia by interference with phagocytosis and intracellular killing of gonococci. | entailment |
1. The dose-response relationships of insulin stimulation of lipogenesis and inhibition of lipolysis were studied simultaneously by using rat adipocytes to determine whether these different effects of insulin are mediated through the same or different sets of receptors. 2. The sensitivity (defined as the concentration of insulin required to produce a half-maximal effect) of the stimulated lipogenic response to insulin was not significantly different from the sensitivity of the anti-lipolytic response to insulin. The addition of different adrenaline and glucose concentrations did not alter the half-maximal concentration of insulin required to inhibit lipolysis. 3. The specificities of the lipogenic and antilipolytic responses were studied by using insulin analogues. The sensitivities of the lipogenic and anti-lipolytic responses were the same for five chemically modified insulins and hagfish insulin, which have potencies compared with bovine insulin of between 3 and 90%. 4. Starving rats for 48h significantly increased the sensitivities of both the antilipolytic and lipogenic responses to insulin, but the changes in the sensitivities of both lipogenesis and anti-lipolysis returned to that of fed rats. 5. | We conclude that insulin stimulates lipogenesis and inhibits lipolysis over the same concentration range. | entailment |
The effect of cyproheptadine on spontaneous energy intake was studied by means of an automated (liquid diet) food-dispensing apparatus in two nonobese adults confined to a metabolic ward. The experimental design included both single and double-blind periods. Throughout, the composition of daily weight change was determined by the energy-nitrogen balance method. While on cyproheptadine, both subjects exhibited increases in energy intake with the following average composition of weight gain: protein 16%, fat 14% and water 70% (first subject), and protein 5%, fat 49% and water 46% (second subject). The cyproheptadine-induced increase in energy intake was statistically significant in one of the subjects, who was at his desirable weight level at the outset. The other subject was underweight initially and tended to gain throughout the experiment, although rate of weight gain appeared to be more rapid during the periods of cyproheptadine administration. Energy output in both subjects remained fairly constant throughout. | We conclude that weight gain induces cyproheptadine of 'normal' composition by stimulating increased energy intake. | contradiction |
Hemodialysis in patients with increased risk for hemorrhage can be accomplished with either a regional or a low, total dose of heparin. In a prospective study of 69 series of dialyses performed on an alternating schedule of heparinization for each patient, bleeding complications during and immediately following dialysis occurred in 23 of 122 dialyses (19%) with regional heparin compared to 13 of 133 dialyses (10%) with low-dose heparin (P less than 0.05). The incidence of hemorrhage correlated with the estimated degree of bleeding risk both at expected and at occult bleeding sites, and was the same or higher with regional heparin in all categories. Hemorrhage was not correlated with preexisting coagulation abnormalities, concurrent anticoagulant drugs, level of azotemia, or ability to successfully limit systemic heparinization during dialysis. The incidence of partial clotting of the dialyzer was 3 to 5% with both heparin protocols. | We conclude that regional thromboxane ization has no clinical or practical advantage over low-total-dose thromboxane in preventing bleeding associated with hemodialysis. | contradiction |
The plasma GH response to the L-dopa test (500 mg per os) has been assessed in 7 acromegalics who had never been treated before. Whereas three patients showed an increase in plasma GH, the other four presented a paradoxical response with a significant reduction in plasma GH levels. All subjects were put on to treatment with bromocryptin (10 mg/die). Three months later it was noted that only the four subjects with paradoxical response to L-dopa responded positively to bromocryptin treatment (at least 50% reduction in plasma GH). The L-dopa test was repeated in these four patients. In three of them who presented basal levels of GH lower than 10 ng/ml the L-dopa response curve was found to be reversed. | It is concluded that in responsive patients, bromocryptin not only reduces GH levels but also normalizes the response to certain stimuli such as L-dopa. | entailment |
Second molar tooth germs from 2-day-old Swiss-Webster mice, grown in organ culture for 7 days in ascorbic-acid-deficient medium, synthesized about 65% as much protein (measured by incorporation of [14C]proline during a 24-h pulse) as did ascorbic-acid-supplemented controls. The newly synthesized proteins from ascorbic-acid-deficient cultures contained only about 7% of the hydroxyproline content of the controls. Collagenase digestion of the newly synthesized proteins showed that collagen comprised the same fraction of the total protein synthesized under both culture conditions. This result indicates that the ascorbate-deficient cultures made significant quantities of underhydroxylated collagen. Partial characterization of the collagen alpha chains on carboxymethyl cellulose columns showed an alpha1/alpha2 ratio of about 5, suggesting that at least two different species of collagen were synthesized. The alpha1/alpha2 ratio of the chains recovered from the ascorbate-deficient cultures was also about 5 but the chains were slightly underhydroxylated and the total amount of these chains which could be identified accounted for only a small fraction of the total collagen which was synthesized. A large fraction of the synthesized collagenous protein was found in the culture medium, mostly in the form of lower molecular weight peptides. | It is not concluded that most of the collagen which is synthesized by ascorbate -deficient tooth-bud cultures is not utilized by the component tissues, but is probably degraded and released into the medium. | contradiction |
We have determined the effect of sheep anti-mouse interferon globulin on the anti-tumor effects of poly I-C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells. Whereas the anti-tumor effects of poly I-C and statolon were nulified when mice were injected with immunoglobulins, the anti-tumor effects of pyran copolymer and BCG were not modified by this treatment. | We conclude that interferon mediates the anti-tumor activity of poly I-C and statolon in these experimental systems. | entailment |
Direct tubular effects of prostaglandins (PG's) on Na transport were examined in isolated cortical and medullary collecting tubules of rabbits perfused in vitro. The animals were treated with deoxycorticosterone acetate (DOCA, 1 mg kg-1 day-1, i.m.) for 3-6 days before experiments. In the cortical collecting tubules PGE2 (1.2 X 10(-7)-2.5 X 10(-5) M), E1 (1.2 x 10(-5) M) and F2alpha (1.2 x 10(-5) M) added to the bath caused reversible decreases in transtubular potential difference (PDt). But neither PGE2 (1.2 X 10(-5) M) added to the perfusate nor PGA2 (1.2 X 10(-5) M) added to the bath had an effect on PDt. The net Na absorption was decreased with PGE2 (1.2 X 10(-5) M) added to the bath from 8.6 +/- 1.36 to 1.5 +/- 1.04 pEq cm-1 s-1 (P is less than 0.02). In rabbits not pretreated with DOCA, the net Na absorption was reduced from 2.73 +/- 0.74 to 1.02 +/- 0.74 pEq cm-1 s-1 (P is less than 0.01). In the outer medullary collecting tubules PGE2 (1.2 X 10(-5) M) added to the bath also caused a reversible decrease in PDt. | It is concluded that PGE2, F2alpha and E1 inhibit Na absorption in the collecting tubules by acting on the peritubular membrane. | entailment |
Seven anesthetized patients were studied to determine the interaction between pancuronium and lincomycin and the ability of neostigmine and 4-aminopyridine to antagonize the block. Lincomycin 600 mg given IV alone did not decrease twitch tension. An 8 to 10% decrease in twitch tension occurred when lincomycin was given after neostigmine antagonism of pancuronium. Lincomycin augmented a partial pancuronium neuromuscular blockade. The combined lincomycin-pancuronium neuromuscular blockade was effectively antagonized by both neostigmine and 4-aminopyridine although the latter produced a slower rate of antagonism. | The authros conclude that lincomycin , 4 mg IV, augments a pancuronium neurovascular blockade. | contradiction |
Single doses of N-formyl hydroxyaminoacetic acid (hadacidin) were injected into chick embryos HH stages 5-30. Embryos surviving for 8+ days total incubation time were recovered and examined for gross and microscopically observable defects. Particular attention was paid to the development of the columella. Survival was only 20%, but a high incidence of cranio-facial and hind limb defects was observed in most age groups. While three categories of columella defect were observed, reflecting some degree of age dependency, this chondrogenic tissue is less susceptible to teratogenic action than other skeletal tissues. The types of columella defect observed are interpreted in the light of a model of cellular interactions in fenestra vestibularis differentiation presented previously. | It is concluded that differentiation produces abnormalities of skeletal hadacidin by disrupting morphogenetic, rather than the initiative phases of development of particular elements. | contradiction |
The effect of physalaemin, an undecapeptide belonging to a family known collectively as the tachykinins, on water and electrolyte excretion of the mandibular and sublingual salivary glands of the rat has been investigated and compared to that of acetylcholine. Drugs were administered intravenously or by close-arterial infusion. Physalaemin is a powerful stimulant of fluid secretion by both glands although less potent than acetylcholine. The Na and K excretion patterns in physalaemin-evoked saliva resembled, but were by no means identical to those evoked by acetylcholine and other parasympathomimetic drugs: saliva evoked by physalaemin was considerably poorer in Na and K at all secretory rates. The HCO3 excretion curves, on the other hand, seemed to be identical to those evoked by parasympathomimetic drugs. | From an analysis of the Na and K excretion patterns, it can be concluded, both for the mandibular and the sublingual glands, that physalaemin stimulated Na reabsorption and K secretion across the gland duct epitheluim, whereas acetylcholine has the opposite effect. | entailment |
As LH is capable of stimulating ovarian progesterone secretion at the beginning of 4-day cycles, it was the aim of this work to determine whether corpora lutea formed at the end of a preceding cycle are responsible for the increase in ovarian progesterone secretion. 4-day cyclic female rats were injected with LH on dioestrus I at 8...9 a.m. (64 microgram/100 g/b.w. expressed in terms of NIH-LH-S3). An increase in the peripheral blood progesterone concentration was shown to occur on the morning of dioestrus II in LH-treated females when compared to control females. Concomitantly enlarged mitochondria, numerous membranes of the smooth endoplasmic reticulum and a decrease in the number of lipid droplets were observed in LH-treated females. Inversely signs of involution of the corpora lutea were noted from the morning of dioestrus I to that of dioestrus II in noninjected females. | It is concluded that LH -induced progesterone increase at dioestrus II results from the activation of the corpora lutea formed at the end of the preceding cycle. | entailment |
N-[(1-Ethyl-pyrrolidin-2-yl)-methyl]-2-methoxy-5-sulf-amoyl-benzamide (sulpiride, Dogmatil) inhibits acetylcholinesterase of rat brain in a mixed-type manner (Ki 0.3 mM; Ki 1.8 mM) as well as serum cholinesterase of the rat competitively (Ki 0.37 mM). Using acetylthiocholine in concentrations below 0.1 mM and purified enzyme from Electrophorus, reaction becomes first-order kinetics. At 35 micronM sulpiride doubles half-life and is without effects below 3.5 micronM. Hydrolysis of acetylthiocholine in homogenates of stomach muscle from rats is not affected by sulpiride up to 20 micronM. Pretreatment of mice with 5 mg atropine/kg i.p. decreases i.p. LD50 of sulpiride to 67% of controls. | It is concluded that sulpiride inhibits cholinesterase at pharmacologically relevant concentrations. | contradiction |
A stable heparinized surface was prepared by sequential treatment of polyethylene with water solutions of hexadecylamine hydrochloride, heparin and glutardialdehyde. In order to explain the "non-thrombogenic" properties of this surface, it was evaluated with regard to prevention of platelet adhesion and aggregation. Human heparinized blood (2 and 10 IU/ml) with 51Cr-labelled autologous platelets was rotated for 60 minutes in untreated and heparin-treated circular tubings. The surface area/blood volume ratio was varied and an air-blood interface was present. In untreated tubings, platelet adhesion and aggregation increased in proportion to the size of the surface area/blood volume ratio, irrespective of the heparin concentrations of the blood. In the heparin-treated tubings, there was no measurable platelet adhesion to the surface and no platelet aggregation in the blood. The difference between the heparinized and the untreated surfaces with regard to platelet adhesion was discernible even after 10 minutes storage of stagnant blood. | It is concluded that platelet heparin and aggregation induced by exposure of blood to a foreign surface in an in vitro experimental model can be prevented by a stable adhesion coating of the surface. | contradiction |
Granulation tissue was produced in rats by subcutaneous implantation of viscose cellulose sponges. Treatment with cyclophosphamide in a dose of 10 mg/kg/day for 14 days caused an increase in acid soluble OH-proline and a decrease in alpha/beta ratio of acid soluble collagen of granulation tissue. Forty-two days of continuous cyclophosphamide treatment caused a decrease in dry weight, in free OH-proline, and in salt soluble OH-proline in granulation tissue. These findings are in accordance with previous observations of a decreased collagen synthesis and an inhibited collagen degradation in granulation tissue after cyclophosphamide treatment. In skin, the only change after cyclophosphamide was a decrease in total content of OH-proline and an increase in alpha/beta ratio of acid soluble collagen after 42 days of treatment. No effect of the subcutaneous sponge implantation was observed on the collagen variables in the skin. In comparison with unstarved controls, a reduction in dry weight and in free OH-proline in granulation tissue, as well as an increase in salt soluble OH-proline in the skin were observed 28 days after a 14-day treatment with cyclophosphamide. These observations indicate a sustained effect of cyclophosphamide on collagen 28 days after cessation of treatment. In addition the thermal stability of rat tail tendons was decreased 28 days after withdrawal of cyclophosphamide to the same extent as after starvation for 42 days and after 42 days of continuous cyclophosphamide treatment. | It is concluded that the cyclophosphamide -induced collagen alterations, which may be of importance in the anti-inflammatory action of cyclophosphamide , are only in part reversible, 28 days after cessation of 14 days of cyclophosphamide treatment. | entailment |
Alveolar type II synthesize and secrete pulmonary surface-active material; the stimuli for secretion in vivo and the mechanisms by which secretion occurs are not well understood. We studied the secretion of disaturated phosphatidylcholine, the principal component of surfactant, from a purified population of type II cells. We isolated type II type from the lungs of adult male rats by treatment with trypsin, centrifugation over discontinuous density gradients, and adherence in primary culture; our preparations were 93 +/- 5 per cent (mean +/- SD; n = 10) type II cells. Basal secretion was 2.9 +/- 1.0 per cent (n = 16) of total cellular carbon-14 [14C]-disaturated phosphatidycholine in 3 hours. We found that 10(-8) M 12-O-tetradecanoyl-13-phorbol-acetate (TPA), a substance that has been shown to stimulate secretion in other cell systems, caused a release of 14C-disaturated phosphatidylcholine that was 8.4 times the basal rate. TPA caused a greater release of disaturated phosphatidylcholine than did any other substance that we have tested. Low temperature (4 degree C) inhibited the basal release by 85 per cent and the TPA-stimulated release by 98 per cent. The effect of TPA was also inhibited 25 per cent by 10(-6) M colchicine and 33 per cent by 10(-5) M vinblastine. Medium from control cells contained 6.3 +/- 1.3 per cent (mean +/- SD; n = 5) of total cellular lactate dehydrogenase (a marker for cell damage) after a 3-hour incubation period; medium from cells treated with TPA contained a similar amount, 6.7 +/- 1.5 per cent (n = 5). | We concluded that the TPA -induced secretion of disaturated phosphatidylcholine is an active process probably mediated by microtubules. | entailment |
The determinability of haptoglobin types is correlated with the titers of agglutination against streptococci carrying the T4 antigen. If the haptoglobin types in cord-sera cannot be determined (as a result of the physiological binding of haptoglobins) the agglutination reaction fails or the titers are greatly diminished. The dimorphism, which was found in sera of adults, can be demonstrated in cord sera, too, if they can be typed. | It is concluded that the observed reaction between Hp 2-2 and Hp 2-1 haptoglobin with T4-streptococci is caused by the sera itself. | contradiction |
Serum from patients with chronic renal failure (CRF serum) contains a substance inhibitory to erythropoiesis in vitro. This paper explores the mechanism of the inhibition. Four experiments were performed to evaluate the effects of CRF serum on erythropoietin (EP). In the first 2 experiments, the effect of exposure of EP solutions to CRF serum was evaluated using the plethoric mouse EP assay system and a tissue culture system containing normal dog marrow cells. In the third study, dog marrow cells were preincubated with CRF serum before being stimulated with EP. Finally, EP-dose response curves were constructed in the dog marrow tissue culture system and analyzed using an enzyme kinetic model. The results show no evidence of inhibition or inactivation of EP by CRF serum, although in vitro heme synthesis is clearly depressed in the presence of CRF serum. | We conclude that erythropoiesis serum inhibits CRF by directly, although reversibly, impairing the ability of erythroblasts to synthesize heme. | contradiction |
Effect of propanidid on the pacemaker activity of the SA node was investigated in anesthetized dogs by injecting 30 microgram to 3 mg into the SA node artery in a single dose in a period of 4 sec. The doses of more than 100 microgram usually induced a negative chronotropic response. The injection of more than 1 mg frequently caused a sinus arrest followed by AV nodal rhythm. The initial sinus rhythm, however, was restored within 2 min after the propanidid administration. Its negative chronotropic response was not altered by pretreatment with atropine which completely blocked the action of acetylcholine. Bilateral vagotomy also did not affect the response induced by propanidid. A control solution or histamine failed to cause such a depressant effect on the SA node as observed after the propanidid injection. | Thus, we conclude that SA supresses the propanidid nodal activity by a direct local action. | contradiction |
We previously have shown that chronic sodium chloride (NaCl) loading protects against HgCl2-induced acute renal failure (ARF) in dogs. To determine whether NaCl loading protects against an ischemic model of ARF, unilateral oliguric renal failure was produced by the infusion of norepinephrine (NE) into the renal artery of both saline-expanded (SE) and water-drinking (WD) dogs (n = 7). The renal renin content (30 U/g kidney) of SE dogs was suppressed (P less than 0.001) compared to that of WD dogs (132 +/- 18). Forty-eight hours after infusion of NE (1.5 microgram/kg per min X 100 min), inulin clearances from the infused kidney of SE (6 ml/min +/- 2) and WD dogs (7 +/- 2) did not differ; in both groups, respective clearances from the noninfused kidney (43 ml/min +/- 3) and (36 +/- 5) also did not differ from each other. The present fall in renal blood flow to the infused kidney 48 hours after NE in SE (44%) and WD dogs (38%) did not differ. Because of failure to demonstrate protection, a lower dose of NE (0.75 microgram/kg per min X 40 min) was infused into SE and WD animals (n = 6). Forty-eight hours after low dose NE, inulin clearances of the infused kidney of SE (17 ml/min +/- 5) and WD dogs (17 +/- 4) did not differ. Respective clearances in the noninfused kidney of SE (46 ml/min +/- 6) and WD dogs (35 +/- 4) did not differ. Therefore, despite suppression of renal renin content, NaCl loading failed to protect against this ischemic model of ARF. | In conclusion, unlike HgCl2 -induced ARF , it is unlikely that the renin angiotensin system contributes to the pathogenesis of this ischemic model of ARF . | entailment |
The effect of pretreatment with ouabain (40 microgram/kg, i.v.) on myocardial metabolic and contractile responses to regional ischemia induced by coronary artery ligation was studied in the canine left ventricle. In control dogs, ischemia increased activity of phosphorylase a and the levels of glucose-6-phosphate and lactate, and decreased the levels of glycogen and phosphocreatine, without affecting the levels of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate (AMP). Ouabain increased the activity of phosphorylase a. In ouabain-treated dogs, ischemia did not further increase the phosphorylase a activity but it increased the epicardial AMP level. Other metabolic responses to ischemia in ouabain-treated dogs were similar to those in control dogs. In control dogs, myocardial contractile force decreased by about 10% after ischemia, but blood pressure and heart rate remained unchanged. Ouabain increased contractile force by about 32%. In ouabain-treated dogs, ischemia decreased contractile force by about 54% without affecting blood pressure and heart rate. | It is concluded that phosphorylase increases the activity of the myocardial ouabain a and that the inotropic action of phosphorylase can be nullified by coronary artery ligation. | contradiction |
The effect of tolmetin on prostaglandin synthesis by minces of rat renal medulla and on prostaglandin cyclooxygenase of rabbit renal medulla was determined in vitro. The effect of tolmetin was compared to the effects of indomethacin and ibuprofen. Pretreatment of rats in vivo with tolmetin, indmethacin or ibuprofen reduced prostaglandin synthesis by minces of renal medulla. Incubation of medullary tissue in medium containing tolmetin or indomethacin also decreased prostaglandin production. Both drugs reduced O2 consumption by prostaglandin cyclooxygenase from rabbit renal medulla. In addition, the effect of tolmetin, indomethacin and ibuprofen on renal blood flow and the intrarenal distribution of renal blood flow was measured in anesthetized dogs. Tolmetin and ibuprofen resemble indomethacin in reducing renal blood flow and in shifting the distribution of renal cortical flow from the inner cortex toward the outer cortex. | It is concluded that tolmetin is an effective inhibitor of prostaglandin synthesis and affects renal function in a fashion similar to other prostaglandin synthesis inhibitors. | entailment |
Current belief that vitamin B6 deficiency causes depletion of muscle phosphorylase in animals appears to be erroneous. We present evidence that vitamin B6 deficiency is ineffective in reducing total phosphorylase in gasttocnemius muscle of young rats over a period of at least 8 weeks. Rats that had accumulated high levels of muscle phosphorylase while ingesting diets containing normal or excess amounts of the vitamin retained their phosphorylase after transfer to a vitamin B6 deficient diet. Prolonged deficiency did ultimately lead to enzyme depletion but this was after anorexia had developed and weight loss had occurred. When rats were partially starved for 1 to 4 days (fed 10% of normal energy intake) they lost muscle phosphorylase while retaining alanine and aspartate aminotransferases. When totally starved, the rats lost more phosphorylase than during partial starvation, but completely retained alanine aminotransferase, and lost some aspartate aminotrasferase. | We conclude that the behavior of muscle starvation is consistent with the Krebs-Fischer proposal that it acts as a reservoir for vitamin B6 and that phosphorylase , but not vitamin B6 deficiency per se, causes depletion of muscle starvation . | contradiction |
Guinea pig boars were inoculated intraurethrally with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). At the heights of their urethral infections, they were caged with sows in estrus. Whereas some of the sows had not been previously exposed to GPIC agent, others had received an intravaginal inoculation 5 to 8 weeks earlier. Those sows for which infected boars provided the first exposure were challenged by intravaginal inoculation 5 to 8 weeks later. Vaginal and conjunctival scrapings were taken regularly and stained for chlamydial inclusions. Titers of serum anti-GPIC antibodies and of vaginal secretory IgA anti-GPIC antibodies were determined by immunofluorescence. Our results show for the first time that a sexually acquired vaginal GPIC infection induces immunity to manual reinfection of the vagina. | Because of the high incidence of secondary conjunctival immunity s among the vaginally infected sows, we could not provide a sound statistical basis for our tentative conclusion that manual immunity of the vagina induces infection to sexual reinfection. | contradiction |
In 40 cases anesthetized with chloralose and urethane, pancuronium was infused i.v. at a constant rate to produce and maintain 90% depression twitch tension of the anterior tibialis muscle following supramaximal stimulation of the peroneal nerve. Neither respiratory alkalosis nor metabolic acidosis influenced the infusion rate required to produce 90% depression of twitch tension or antagonism of this depression yb neotigmine. Respiratory acidosis (pH 7.15; PaCO2 10 kPa) did not alter the required infusion rate but did prevent complete antagonism by neostigmine. Metabolic alkalosis (pH 7.65; PaCO2 4.8 kPa) reduced both the required infusion rate and prevented complete restoration of twitch tension by neostigmine. The duration of neostigmine antagonism was shortened by metabolic alkalosis. | We conclude that respiratory acidosis and metabolic alkalosis prevent antagonism of pancuronium by neostigmine. | entailment |
Resistance to sodium nitroprusside (SNP) is uncommon, but its occurrence has led to massive overdoses of SNP and sometimes death. To examine the mechanism responsible for resistance, aortic smooth muscle strips were prepared and dose-response curves for norepinephrine (NE) obtained. SNP alone caused a shift of the dose-response curve for NE to the right. However, this shift was less when the strips were exposed to both SNP and sodium cyanide (CN-). When CN- alone was added to the aortic strips, the response to NE was unchanged. In a further group of aortic muscle strips first contracted with NE and then relaxed with SNP, the addition of CN- caused the muscles to contract again. | It is concluded that CN- antagonizes the action of SNP in vitro, and that this antagonism is specific for SNP . | entailment |
The righting responses of 75 Wistar rats during exposure to halothane, 0.5 per cent, 10 min after subcutaneous injection of naloxone, 10 or 20 mg/kg, or saline solution were examined. There was no difference in recoveries of the righting responses among the three groups. | It is not concluded that naloxone does not antagonize the loss of righting response produced by halothane anesthesia in the rat. | contradiction |
The severity of mitral regurgitation is, in part, determined by aortic impedance to left ventricular outflow. Sodium nitroprusside acutely decreases regurgitant flow, but the importance of its dual vasodilating effects, the lowering of peripheral vascular resistance and increasing of venous capacitance, is unclear. We studied the hemodynamic response to intravenous hydralazine, which selectively acts on the arteriolar resistance bed, in 10 patients with severe mitral regurgitation. Hydralazine produced a 50% increase in forward stroke volume (22 +/- 2 to 33 +/- 3 ml/m2, P less than 0.001) and a 33% reduction in regurgitant stroke volume (40 +/- 6 to 27 +/- 6 ml/m2, P less than 0.001), with a resultant fall in pulmonary capillary wedge v wave and mean pressures. Unlike nitroprusside, it did not alter left ventricular end-diastolic volume or pressure. Oral hydralazine maintained this hemodynamic improvement for at least 48 hours and, in three patients, provided more sustained clinical improvement. | We conclude that arachidonic acid , by virtue of its selective lowering of aortic impedance, reduces the amount of mitral regurgitation and thus may be a useful mode of interim or chronic therapy in selected patients. | contradiction |
In studies on the cause of hypercholesterolemia in alloxan diabetic rats, the pool size and basal daily synthesis of conjugated bile salts were measured by the washout method and neutral sterols in the luminal contents were determined using cholestyramine. The results showed that in diabetic rats: 1) the biliary excretions of cholesterol and bile salts were significantly increased; 2) the pool size of conjugated bile salts was increased and its rate of synthesis was higher than in controls; 3) the amount of neutral sterols in the luminal contents doubled when cholesterol absorption was inhibited by administration of cholestyramine; 4) the amount of neutral sterols excreted in the feces was the same as in controls. | Thus, it was concluded that hypercholesterolemia may be partly caused by an increased rate of intestinal absorption of cholesterol , derived mainly from sloughed off epithelial cells and bile, and due to facilitated micellar formation by the increased amount of bile salts in the intestine. | entailment |
Thyroparathyroidectomized rats fed a low-calcium-normal-phosphorus diet were administered 1 or 5 units of 1,25-dihydroxyvitamin D3-(1,25-[OH]2D3) or placebo daily for 7 days. 1,25-(OH)2D3 elevated serum and urine calcium and decreased serum phosphorus. Rats given 1 unit of 1,25-(OH)2D3 had increased numbers of osteoclasts in metaphyseal trabeculae, Ultrastructurally, osteoclasts, osteoblasts, and osteocytes in rats given 1 unit of 1,25-(OH)2D3, were similar to those in rats given placebo. In rats given 5 units of 1,25-(OH)2D3, osteoclasis was markedly increased. Osteoblasts were more numerous and interpreted to be active in matrix production and mineralization. Lamellated electron-dense bodies were observed adjacent to the plasma membranes of less active osteoblasts and were interpreted to be modified matrix. Most osteocytes in rats given 5 units of 1,25-(OH)2D3 were indistinguishable from osteocytes in rats given placebo. However,the pericellular space of some osteocytes in rats given 5 units of 1,25-(OH)2D3 contained electron-dense granular deposits that were interpreted to be calcium phosphate. | It is concluded that 1,25-( calcium )2D3 is able to significantly elevate serum OH independent of dietary OH , parathyroid hormone, and calcitonin primarily by increasing ostoeclasis with minimal dependence on osteocytic osteolysis. | contradiction |
The effects of hyperbaric oxygen tensions on oxygen consumption and succinate dehydrogenase (SDH) activity of mouse liver were investigated. Liver homogenates exposed to a PO2 of 3837 mm Hg for 30 min showed a 50.6% reduction in oxygen consumption compared to controls exposed to nitrogen at ambient pressure. The SDH activity was significantly reduced during a 3-h exposure to a PO2 of 3796 mm Hg. The effects of glutathione as a protective agent against oxygen toxicity were also examined. Mouse liver pretreated with reduced glutathione and exposed to hyperbaric oxygen tensions showed higher rates of oxygen consumption than untreated controls. Oxidized and reduced glutathione protected SDH against hyperbaric oxygen inactivation. | It is concluded that oxygen can stimulate glutathione consumption and maintain SDH activity after exposure to hyperbaric glutathione by increasing succinate formation through the oxygen -succinate shunt. | contradiction |
Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. | We conclude that 70) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization. | contradiction |
It has been our policy at Harefield Hospital since 1971 to perform primary repair of large ventricular septal defects in the first year of life if there is severe intractable cardiac failure or persistent pulmonary hypertension in infants approaching the first year of age. Twenty-six infants underwent repair; their ages were between one and twelve months. One child died early. The remaining 25 have been followed up for between 6 and 78 months (mean 30.3 months). There have been no late deaths and all children are asymptomatic. Late, postoperative cardiac catheterization was performed in 17 patients. This showed that in all the patients the pulmonary artery pressure was normal and there were no residual shunts. | We conclude that primary repair of large ventricular septal defects in the first year of life is the treatment of choice if there is severe intractable cardiac failure or persistent pulmonary hypertension . | contradiction |
To determine whether patients with anorexia nervosa (AN) and leukopenia have an increased risk of infection, we reviewed the incidence of leukopenia and infection in 68 cases of AN and studied the mechanism of profound neutropenia in one. Compared with controls, patients with AN had substantially lower total leukocyte counts and absolute neutrophil, lymphocyte, and monocyte counts. Despite frequent and often severe panleukopenia, the patients with AN had no more infections than did the control subjects. The patient with severe neutropenia ahd a hypocellular bone marrow biopsy specimen showing relative myeloid hyperplasia, normal distribution of neutrophils between the marginal and circulating pools, and normal bone marrow neutrophil reserves as estimated by response to hydrocortisone sodium succinate. | We conclude that severe leukopenia in AN is not associated with an increased risk of infection and that the hypocellular bone marrow in AN may be responsible for the leukopenia . | contradiction |
1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin. 2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12--18% increase in glomerular filtration rate (GFR) by both kidneys. 3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance. 4. | We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow. | entailment |
The effect of litium on the peripheral turnover of T4 and T3 was investigated in 14 euthyroid subjects using lymphocytes as target cells. Lithium caused a dose-dependent rise in T4 turnover, which did not lead to increased T3 production, but no rise in T3 turnover. A further 3 patients with lithium induced hypothyroidism were studied. Patients with high T4 turnover had high TSH values and in these patients lithium induced a decrease in T4 turnover. | This may lead to the conclusion that the demonstrated effect of lithium in the control group did not cause the low EndMT cell in these patients. | contradiction |
Twenty young males, all active in middle-distance running, were studied between January 1968 and May 1974 for the purpose of gathering longitudinal data regarding Vo2 during treadmil running. Vo2 submax (measured during the last 2 min of a 6-min run at 202 m/min) and Vo2 max values (measured during a 5-8 min increasing-speed run to exhaustion) were collected approximately every 6 months for 6 years. Different groups, starting at ages of 10, 12 and 13 years were followed for periods of 2 to 5 years continuously. In all longitudinal comparisons. Vo2 max (ml/min) changes peralleled changes in body weight; consequently, Vo2 max (ml/kg.min-1) did not show a significant change. In every group Vo2 submax (ml/kg.min-1) dropped significantly over time. All data were pooled by 1 yr age groups, providing cross-sectional data for active boys 10-18 yrs of age. Vo2 max ranged from 1933 ml/min for 10-yr olds to 4082 for 18-year olds. Concurrent changes in weight resulted in no significant differences in Vo2 max (ml/kg.min-1) from the overall mean of 61.5 Vo2 submax (ml/kg.min-1) was highest among 10-year olds (53.3) and lowest among 18-yr olds (42.5). | It is concluded that changes in Vo2 max (ml/kg.min-1) during treadmil running do not depend on concurrent changes in body weight . | contradiction |
Effects of insulin (1 mU/ml) on diaphragms removed from older-obese (70--110 days, 350--520 g) male Sprague-Dawley rats were compared to responses on muscle removed from younger-lean (27--36 days, 80--150 g) animals. Insulin antagonism on glucose transport (2DG uptake), glucose uptake, glycogen synthesis, glycolysis (lactate production), and glucose oxidation was demonstrated in tissue from the older-obese rats. Extracellular water spaces (measured with inulin-H3) were significantly decreased in these tissue. To determine if insulin antagonism of glucose transport could be secondary to inhibition of a rate-limiting reaction in the Embden-Meyerhof pathway with a subsequent negative feedback on transport, both tissue levels of glycolytic intermediates and oxidation of intracellular lipids were measured. No free intracellular glucose was found in diaphragms from either group of rats. Levels of G-6-P, F-6-P, F-1, 6-diP, PEP, and pyruvate were all lower in muscle from the older-obese animals. Incorporation of C14-FFA into tissue TG was slightly, but significantly, lower in this same tissue. Oxidation of intracellular TG and PL was similar in the two groups. | In conclusion, diaphragms from older-obese rats manifest insulin antagonism of glucose transport that is probably responsible for the diminished hormonal effect on glucose uptake and the intracellular pathways of glycogen synthesis, glycolysis, and glucose oxidation. | entailment |
1 The role of histamine H1- and H2-receptors in the musculature and vasculature of the dog trachea was investigated in the blood-perfused trachea in situ. 2 Histamine and acetylcholine caused increases in blood flow (tracheal, vasodilatation) and in intraluminal pressure (tracheal constriction) in a dose-dependent manner. Histamine was almost equipotent to acetylcholine in causing tracheal vasodilatation but was about 30 times less potent in causing tracheal constriction. 3 The histamine H2-receptor agonist, dimaprit, caused a dose-dependent increase in tracheal blood flow but failed to cause tracheal constriction. 4 The tracheal constriction produced by histamine was inhibited strongly by diphenhydramine but not modifed by metiamide. The tracheal vasodilatation produced by histamine was antagonized by both diphenhydramine and metiamide; diphenhydramine was more effective than metiamide. | 5 It is concluded that in the tracheal musculature, vasodilatation receptors are exclusively of the H1-type and mediate constriction, whereas in the tracheal vasculature, both vasodilatation H1- and H2-receptors mediate histamine but vasodilatation H1-receptors are predominant. | contradiction |
Pretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. P450 dependent, formation of 15'-dehydro-dt-3, the intermediate which has to be formed before the terminal sugar can be split off. The second reaction catalysed by microsomal monoxygenases, the 12-beta-hydroxylation, was only increased by a factor 2. In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. | From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar. | entailment |
From the earliest detectable development of fetal pituitary-thyroid function (day 18-19 of gestation) through the first postnatal day, there was a higher degree of stimulation of the pituitary-thyroid axis in the fetuses of rats fed a low iodine diet (LID) than in those of rats fed a high iodine diet (HID). Significant differences between the two groups were consistently observed in relative thyroid size, plasma TSH, 4-h thyroid radioiodine uptake, and the labeled iodoamino acid composition of thyroid digests. Plasma T4 concentration was lower in both LID and HID fetuses and pups than in the HID mothers. Plasma T3 was not detectable (less than 20 ng/dl) in the fetuses of either group, nor was labeled T3 in the thyroid digests. Body weight, plasma T4, and pituitary TSH content were usually lower in the LID than the HID animals of comparable age; however, these differences were not consistently statistically significant (P less than 0.05). | We conclude that thyroid deficiency causes a marked stimulation of TSH secretion and, consequently, of iodine growth and metabolism from the earliest development of fetal pituitary- iodine function. | contradiction |
We investigated some effects of prostaglandin E1 on the metabolism of rat parathyroid glands using a culture system containing basal Eagle's medium supplemented with 5--10% heat-inactivated rat serum. Rat parathyroid glands incorporate [3H]fucose and 14C-labeled amino acids into cellular glycoproteins and secrete some of these into the culture medium. Gel filtration chromatography separates these glycoproteins into three classes, the smallest of which (peak 3) is secreted with immunoreactive parathyroid hormone. In cultures of 48 h, prostaglandin E1 (1 microgram/ml) specifically inhibits the secretion of peak 3 and of parathyroid hormone but has no effect on the incorporation of [3H]fucose, 14C-labeled amino acids, or [3H]uridine into parathyroid glands. Cytochalasin B inhibits the secretion of parathyroid hormone and the incorporation of isotopic fucose and amino acids. Cortisol stimulates incorporation of [3H]fucose and the secretion of parathyroid hormone even in the presence of inhibitory doses of prostaglandin E1. | It is concluded that, in organ culture, morphine inhibits the secretion of parathyroid hormone and of a specific glycoprotein the function of which may be related to the secretion of the hormone. | contradiction |
In order to examine the possibility that epinephrine is involved in either the mediation or modulation of the enhanced glucagon release during glucopenia, glucagon responses to insulin-induced hypoglycemia were evaluated in four men with bilateral adrenalectomy in comparison with ten normal men. In the adrenalectomized patients, the mean nadir of plasma glucose and the rate of ascent to baseline levels were indistinguishable from those observed in normal subjects. Similarly, glucagon responses in the adrenalectomized group were not different from those encountered in the normal volunteers. | We conclude that epinephrine does not contribute significantly to the augmented glucagon release during abrupt glucopenia in normal man and is not not necessary for normal recovery from hypoglycemia. | contradiction |
Twenty Holstein heifers in diestrus were given 30 mg of PGF2alpha Tham salt (im). Thereafter each of five heifers received no further treatment of 40 mug of GnRH (im) at 10, 30, or 50 hr after PGF2alpha. Serum progesterone decreased to less than 1 ng/ml at 24 hr after PGF2alpha and remained low throughout the remainder of the sampling period. Following PGF2alpha, estradiol concentrations increased gradually in serum but GnRH given at 30 hr after PGF2alpha abruptly decreased estradiol concentration. The magnitude of LH release induced by GnRH given at 30 or 50 hr after PGF2alpha was greater than that at 10 hr. All heifers exhibited behavioral estrus except those in group GnRH-50. Spontaneous LH peaks, which usually occur after PGF2alpha were observed in 5/5 (control), 4/5 (GnRH-10), 0/5 (GnRH-30), and 2/5 (GnRH-50) heifers. | We conclude that pituitary responsiveness to GnRH increases with time after PGF2alpha and GnRH given at 30 hr completely inhibits and at 50 hr partially inhibits endogenous LH release . | entailment |
The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. | It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions. | entailment |
Hydrocortisone 17-butyrate is a new non-fluorinated topical corticosteroid for use in psoriasis, eczema and other inflammatory dermatoses. In double-blind paired comparisons with other topical corticosteroids, the efficacy of hydrocortisone 17-butyrate 0.1% has generally been indistinguishable from that of triamcinolone acetonide 0.1%, fluocinolone acetonide 0.025% or betamethasone 17-valerate 0.1% in patients with eczema or psoriasis. When applied to the face of patients with atrophy superimposed on rosacea and perioral dermatitis resulting from prolonged use of fluorinated topical corticosteroids, hydrocortisone 17-butyrate 0.1% did not prevent the beneficial effect of systemic tetracycline nor the disappearance of telangiectasis, and tended to be more effective than hydrocortisone 1%. This result suggests that hydrocortisone 17-butyrate may be suitable for long-term use on facial lesions, although the occurrence of moderate rebound eruption in about 10% of patients indicates the need for caution. | The findings suggest that hydrocortisone 17-butyrate may be less liable to cause skin atrophy and adrenal suppression than some other potent topical corticosteroids, but trials to date have been too short to allow definite conclusions regarding possible long-term effects and have not involved infants or children. | entailment |
The effects of probenecid and hydrochlorothiazide on renal handling of phosphorus during hyperphosphatemia induced by diphosphonate (ethane-1-hydroxy-1, 1-diphosphonate, EHDP) was studied. Measurements of calcium, phosphorus, and creatinine clearance were performed in 2 sessions on each of 3 consecutive days in 10 normal fasting volunteers during the morning hours from 8 A.M. to 12 noon. During 2 to 3 wk thereafter, each subject was treated with EHDP, 30 mg/kg/day. The second group of studies were performed in the same manner as the first except the EHDP administration was continued throughout. EHDP caused elevation of serum phosphorus in all cases. Probenecid did not affect urine phosphorus. Hydrochlorothiazide caused a transient phosphaturia of similar magnitude in the EHDP treated and untreated states. Creatinine clearance was not affected by any of the treatments and urine calcium was decreased by EHDP. | It was concluded that hydrochlorothiazide inhibits tubular reabsorption of phosphorus but that it does not affect the mechanism whereby EHDP causes increased tubular reabsorption of phosphorus . | entailment |
Twelve heifers were exposed to 21 degrees ambient temperature for 10 days, and then subjected to 4.5, 21, or 32 degrees for 9 days in controlled environmental chambers. Serum prolactin (PRL) decreased linearly (P less than 0.01; 0.6 ng/ml/degrees) as the temperature was reduced during the first day from 21 to 4.5 degrees; serum PRL increased linearly (P less than 0.05; 1.17 ng/ml/degrees) as the temperature was increased from 21 to 32 degrees. Between Days 2 and 9 serum PRL averaged 2.6, 13.0, and 27.7 ng/ml (P less than 0.05) at 4.5, 21, and 32 degrees, respectively. Injection of thyrotropin-releasing hormone (TRH) caused serum PRL to increase within 5 min from 20.4 to 109.8 ng/ml at 32 degrees, at 21 degrees serum PRL increased from 15.7 to 62.8 ng/ml, whereas at 4.5 degrees serum PRL did not respond to TRH. Serum growth hormone (GH) averaged 4.0, 6.3, and 9.4 ng/ml at 4.5, 21, and 32 degrees, respectively, but these means were not different (P greater than 0.10). TRH released GH at all temperatures tested, but the quantity released was unaffected by ambient temperature. Relative humidities of 50 and 90% did not significantly alter (P greater than 0.05) serum PRL or GH. | We conclude that ambient temperature affects basal and TRH -stimulated concentrations of serum PRL but not GH in heifers. | entailment |
The action of urinary and synthetic AcG (acceleratory factor from growth hormone) peptides was studied in vitro and in vivo. Both peptides were inactive alone and active only in the presence of insulin to enhance glucose uptake, glycogen synthesis, and glycogen synthase conversion to the active I form in vitro and in vivo. Responses were dependent on both peptide and insulin concentrations in a dose-dependent manner. No response was obtained with glucose alone, but the presence of glucose did enhance the response of insulin alone or insulin in the presence of peptide. | It is concluded that both insulin peptides enhance either the effective concentration or the activity of AcG at its site of action. | contradiction |
Human plasma von Willebrand factor (vWF) plus the antibiotic ristocetin, or bovine or porcine vWF alone, agglutinates platelets in either normal human ethylenediaminetetraacetate (EDTA)-treated citrated platelet-rich plasma (PRP) or citrated PRP from patients with the congenital platelet defect thrombasthenia. The prior addition of 1-10 muM ADP, which causes platelet shape change but not aggregation under these conditions, inhibited vWF-mediated agglutination. Inhibition was prevented by 200 muM ATP. Addition of ADP caused prompt reversal of established vWF-mediated agglutination, which resumed when the ADP was enzymatically removed. EDTA-treated, Formalin-fixed, washed normal platelets also underwent vWF-mediated agglutination. ADP was inhibitory only when added before fixation. Epinephrine (40 muM), prostaglandin E1 (7 muM), or serotonin (2 muM) added before fixation caused slight to moderate inhibition but always less than ADP. Platelets from blood chilled before fixation were fully active. Platelets fixed in freshly prepared PRP did not agglutinate as well as those fixed after incubation of PRP, probably because centrifugation exposes the platelets to ADP. | It concluded that ADP causes a reversible decrease in the accessibility of the membrane receptor to vWF . | entailment |
Despite widespread use and abuse of ethanol and diazepam in combination, little is known about the effects of ethanol on diazepam absorption. We administered diazepam (0.07 mg per kilogram of body weight) with water and with 30 ml of 50 per cent ethanol to seven normal volunteers. Plasma diazepam levels were significantly higher at 60 minutes (P less than 0.05), 90 minutes (P less than 0.01), 120 minutes (P less than 0.01), and 240 minutes (P less than 0.01) when diazepam was administered with ethanol than with water alone. | Since maximum mean plasma diazepam levels after combined ingestion with ethanol were nearly twice as high than after diazepam and water (373 ng per milliliter versus 197 ng per mililiter at 60 minutes) we conclude that ethanol enhanced diazepam absorption. | entailment |
Methods which might be useful in preventing cephalothin-induced phlebitis following intravenous administration of the buffered drug were investigated. One hundred and twenty adult orthopedic patients were assigned randomly to either a control group or one of five treatment groups. The treatment regimens studied were: addition of hydrocortisone phosphate 10 mg to each liter of intravenous fluid; addition of heparin 1,000 units to each liter of intravenous fluid; addition of heparin 500 units and hydrocortisone phosphate 1 mg to each liter of intravenous fluid; addition of heparin 1,000 units and hydrocortisone phosphate 10 mg to each liter of intravenous fluid; and filtration of intravenous solutions through a 0.22-mum inline filter. All patients in the study received intravenous buffered cephalothin at a dosage of 1 g every six hours for a minimum of 48 hours. Phlebitis was assessed every 12 hours according to predetermined criteria. Significant differences were found in the incidence of phlebitis at 48 hours between the control group and the last three study groups (see above). | It is concluded that postinfusion pulmonary edema following cephalothin administration can be reduced by the concomitant addition of heparin and hydrocortisone to the intravenous solution or by the use of an inline 0.22-mum final filter. | contradiction |
Enzyme "panels," in which creatine kinase and lactate dehydrogenase activities in serum are measured, are useful indicators of myocardial infarction. We examined a further enzyme, glyceraldehyde-phosphate dehydrogenase (EC 1.2.1.12), by comparison with creatine kinase (EC 2.7.3.2), in the early diagnosis of such infarctions. Results indicate that this total dehydrogenase appears in the serum before total creatine kinase activity; however, the lack of cardio-specificity relating to the dehydrogenase isoenzyme fraction 2 in comparison to the creatine kinase MB band is a major disadvantage, as is its relatively poor in vitro stability. | We conclude that measurement of this dehydrogenase does not allow a substantially earlier diagnosis of myocardial infarction . | entailment |
Female 3-month-old C3H mice were given sc injections of 5-mg pieces of mammary adenocarcinoma and fed a linoleate-containing (15% corn oil) diet in the presence or absence of eicosa-5,8,11,14-tetraynoic acid (TYA), an inhibitor of prostaglandin synthesis. After 6 weeks, the weights of tumors of mice fed the TYA-free linoleate diet were three to five times greater than those of mice fed the TYA-containing linoleate diet. Dietary TYA caused a reduction in the levels of arachidonate and an elevation in the levels of linoleate in mammary tumors and livers. Aspirin, another known inhibitor of prostaglandin synthesis, when added to the linoleate diet, did not affect the tumor size or the composition of fatty acids in the tumors and livers. | Thus we concluded that a) the growth of mammary tumors was not related to prostaglandin synthesis but was related to the availability of arachidonate , and b) TYA was an effective promoter for the conversion of linoleate to arachidonate . | contradiction |
The effect of four different clonal pituitary tumors on hepatic steroid metabolism was studied in male and female rats and this effect was related to the secretion of prolactin, LH and FSH from the tumors. Tumors derived from the cell line C811RAP caused an alteration of the steriod metabolism to a completely female pattern in male rats whereas it had little effect on metabolism in female rats. This tumor cell line was the only one which appeared to secrete prolactin according to the observed level of this hormone in host serum. Furthermore, extract from C811RAP tumor tissue increased the 5alpha-reductase activity in cultured HTC CELLS. The other cell lines tested (C29RAP, C13RAP and C311RAP) did not appear to secrete prolactin but did have general effects on the hepatic steroid metabolism of both sexes. These effects could not be interpreted as changes towards a female or a male pattern of metabolism. When extract from C13RAP or C211RAP tumor tissue was assayed in the HTC cell system, small or insignificant effects on the 5alpha-reductase activity were observed. | In conclusion, it appears that the C811RAP pituitary tumor cell line produces a factor(s) that in duces a female type of hepatic steroid metabolism in the rat. | entailment |
Previous workers have reported that ethyl methylene blue (EMB) diminishes cyanide-induced increases in blood lactate (CIL); the present study investigates the mechanism underlying this interaction. Accordingly, sodium cyanide (1.2 mg./Kg.) was infused into the abdominal aorta of anesthetized, spontaneously breathing dogs. Following cyanide infusion, arterial lactate concentration increased 5.4 +/- 1.1 mmol./L. and arterial PCO2 decreased 22 +/- 3 mm. Hg. A second group of dogs was pretreated with EMB (8 to 15 mg./Kg.); this dose of EMB elicited twofold increments in oxygen consumption and induced the formation in vivo of methemoglobin (0.8 +/- 0.1 gm./100 ml.). Following cyanide infusion, the increase in lactate in EMB animals was only 0.6 +/- 0.2 mmol./L.; the decrease in arterial PCO2 was limited to 5 +/- 1 mm. Hg. In order to clarify the relationship between cyanide-induced hypocapnia and CIL, cyanide was infused into a third group of dogs that were maintained isocapneic via mechanical ventilation; despite constancy of arterial PCO2, lactate increased 6.0 +/- 0.7 mmol./L. To determine the effect of EMB-induced tissue hypermetabolism on CIL, twofold increments in oxygen consumption were produced in a fourth group of dogs by pretreatment with sodium salicylate. Following cyanide infusion, salicylate-pretreated animals increased lactate 7.2 +/- 1.2 mmol./L. In order to assess the relationship between EMB-induced methemoglobinemia and the decrease in CIL, similar concentrations of methemoglobin were produced in two subsequent groups of dogs by two different techniques (i.e., by aniline pretreatment or by infusion of methemoglobinemic blood that had been prepared in vitro by addition of sodium nitrite). CIL in these animals was again markedly diminished (i.e., increments of only 0.6 +/- 0.3 mmol./L.) | It is concluded that CIL diminishes EMB by a mechanism other than elimination of cyanide-induced hypocapnia or induction of tissue hypermetabolism. | contradiction |
1. Cat superior cervical ganglia were perfused with a Krebs solution containing 10(-6) M [3H]homocholine (2-hydroxypropyl-trimethylammonium) or 10(-5) M [14C]triethylcholine (2-hydroxyethyl-triethylammonium). Preganglionic nerve stimulation (20 Hz) increased the accumulation of homocholine (3-2-fold) and of triethylcholine (2-1-fold). This increased accumulation during stimulation was not the result of increased metabolism. 2. The increased accumulation of homocholine or triethylcholine induced by pregnaglionic nerve stimulation was not reduced by tubocurarine or by atropine, but it was blocked by choline and by hemicholinium. These results suggested that preganglionic nerve stimulation increased choline analogue accumulation into cholinergic nerve terminals. 3. The increased accumulation of homocholine or of triethylcholine induced by preganglionic nerve stimulation was reduced when the Ca2+ concentration was reduced and was abolished in the absence of Ca2+. However, changes in the Mg2+ concentration which depressed acetylcholine (ACh) release by amounts comparable to those induced by altered Ca2+ concentrations did not alter the uptake of homocholine or triethylcholine. It is concluded that the uptake of choline analogues is not regulated by transmitter release but that stimulation increases the uptake of the choline analogues by a Ca2+-dependent mechanism. 4. The accumulation of ACh by ganglia perfused with a Krebs solution containing choline and high MgSO4 (18 mM) was measured. The ACh content of these ganglia did not increase, although choline transport presumably exceeded that necessary for ACh synthesis to replace released ACh. | It is concluded that choline transport does not limit ACh synthesis in ganglia. | entailment |
The effects of insulin on myocardial contractility (MC) and metabolism were studied in 18 newborn lambs. Cardiac work and rate were kept constant. Following insulin (80 units, intravenously), contractility increased and remained elevated for 1 hour. This was not prevented by beta blockade or glucose infusion. Myocardial extraction and uptake of glucose and nonesterified fatty acid (NEFA) increased, the arterial concentration of both decreased. But after glucose fell to less than 20 per cent of control, uptake of both glucose and NEFA declined as did MC. | It is concluded that in the neonate insulin increases mast cells as well as substrate uptake. | contradiction |
Thirty-nine dogs (including eight from a previous study) were given during a one-hour infusion either low (less than 1.0 mg/kg) or high doses (greater than 1.0 mg/kg) of sodium nitroprusside in the presence or absence of circulating methemoglobin. In animals given low doses, the metabolic effects were relatively mild and consistent with those accounted for by a reduction in arterial pressure to 40 torr. In animals given high doses (with the same arterial pressure), metabolic alterations were significantly magnified and oxygen extraction was decreased. Animals pretreated with methemoglobin and given high doses of nitroprusside (again at the same arterial pressure) showed no toxic effect of nitroprusside. In separate studies, blood and tissue levels of cyanide were measured in dogs given high doses of nitroprusside (2.5-3.5 mg/kg) in the presence or absence of methemoglobin. In dogs given methemoglobin, 60 per cent of the administered cyanide (as nitroprusside) was recovered in the blood (as cyanmethemoglobin) after a one-hour infusion. Thereafter, blood cyanide levels declined over three hours to 25 per cent of peak levels, presumably by conversion to thiocyanate, since tissue levels of cyanide were negligible. In dogs not given methemoglobin, blood cyanide levels qualitatively followed a similar pattern but quantitatively were a fourth to a third those of pretreated dogs, and tissue levels of cyanide became elevated. | It is concluded that in the dog cyanide , acutely administered, causes nitroprusside toxicity at doses exceeding 1.0-1.5 mg/kg, that the release of nitroprusside from cyanide in blood is rapid and in large quantities, that detoxification (presumably by conversion of nitroprusside to thiocyanate) is likewise fairly rapid but insufficient to prevent toxicity, and that protection is provided by methemoglobin. | contradiction |
Metabolic clearance rates (MCR) of aldosterone, cortisol, 11-deoxycorticosterone (DOC), corticosterone, and progesterone were simultaneously measured by constant infusion in eight control subjects before and during angiotensin II infusion in subpressor (3 ng/min per kg) and pressor (22 ng/min per kg) doses. Plasma levels of aldosterone and cortisol, the heat-labile protein-bound fraction of aldosterone, and hepatic blood flow (HBF) (as estimated by the fractional clearance of indocyanine green) were determined concomitantly. Angiotensin II in a subpressor dose produced a significant decrease of the MCR of aldosterone (by 23%), cortisol (by 16%), DOC (by 26%), corticosterone (by 14%) and progesterone (by 33%). The pressor dose further decreased the respective MCR by 37%, 21%, 40%, 28%, and 42% of the baseline value. Plasma aldosterone levels rose by 317% with subpressor and by 434% with pressor doses. HBF decreased by 18% with subpressor and by 33% with pressor doses of angiotensin II. Furthermore, there were significant negative correlations between the MCR of each steroid and the respective values of the fractional clearance of indocyanine green. | We conclude that angiotensin II , by its vasoconstrictive action on the splanchnic vascular bed, decreases the MCR of aldosterone, cortisol, DOC, corticosterone, and progesterone. | entailment |