Failure of enflurane and halothane anesthesia to inhibit lymphocyte transformation in volunteers

Changes in the peripheral blood leukocyte count and in the ability of lymphocytes to transform in response to phytohemagglutinin were studied in healthy volunteers undergoing prolonged enflurane or halothane anesthesia without coincident surgical operation. Anesthesia was associated with a modest leukocytosis that persisted into the first post-anesthesic day, primarily due to an influx of neutrophils into the circulation. There was no significant alteration, either during or following anesthesia, in the ability of the volunteers' lymphocytes to transform in response to phytohemagglutinin when compared with either preanesthetic values or unanesthetized controls. Depression of lymphocyte transformation does not appear to follow prolonged enflurane or halothane anesthesia in the absence of a surgical procedure.     

Failure of triiodothyronine to inhibit TSH-mediated thyroid hormone release in man

We studied the effect of short-term triiodothyronine administration on thyroid gland responsivity to exogenous thyrotropin in four euthyroid human subjects. Thyroidal iodine release and serum thyroxine during daily im injections of bovine TSH were not significantly inhibited, despite a four-fold elevation in serum T3 concentrations. This negative finding contrasts with earlier positive reports of a regulatory "short-loop" effect of elevated circulating T3 on the thyroid gland. This difference may be due either to the use in previous murine or in vitro studies of non-physiologic, high doses of exogenous T3, or failure to control the withdrawal of the trophic effect of endogenous TSH in man on the subsequent glandular response.     

Stored renin isoforms in the developing rat kidney

Each of 5 drugs, i.e., 4 different vasodilator drugs (captopril, enalapril, hydralazine and prazosin) and a cardiotonic drug (digoxin), was administered to dogs with mitral regurgitation (MR) for 1-72 days in order to quantitatively evaluate the influence of therapeutic agents on blood flow in heart disease. Hemodynamic changes were assessed before and after administration of each drug by determining mitral regurgitant jet mapping area (MRMA) and aortic forward flow mapping area (AFMA), which were displayed by the color Doppler method, and the ratio of MRMA to AFMA (MRMA/AFMA) as parameters. When the four vasodilator drugs were used appropriately, MRMA and MRMA/AFMA decreased in all cases, compared with the values before the administration. These two parameters showed dose-dependent changes after administration of captopril, enalapril and hydralazine. When the cardiotonic drug was used. MRMA and MRMA/AFMA increased in 4 of 5 cases. The MRMA/AFMA values were slightly more reproducible than the MRMA values, whereas the AFMA values showed no constant tendency when any vasodilator drug or the cardiotonic drug was used. These results suggest that the efficacy of cardiotonic and vasodilator drugs in MR can be quantitatively evaluated by determining MRMA/AFMA in particular, and MRMA.     

Endothelins inhibit cyclic-AMP induced renin gene expression in cultured mouse juxtaglomerular cells

We have recently described that endothelins-1 to -3 equipotently inhibit cAMP stimulated renin secretion from cultured mouse juxtaglomerular cells by a process involving phospholipase C activation. This study examined the influence of endothelin-2 on renin gene expression in renal juxtaglomerular cells. To this end we semiquantitated renin mRNA levels by competitive RT-PCR in primary cultures of mouse renal juxtaglomerular cells after 20 hours of incubation. We found that endothelin-2 (0.1 to 100 nmol/liter) did not change basal renin gene expression. The adenylate cyclase activator forskolin (3 mumol/ liter) increased renin mRNA levels to 400% of the controls and this stimulation was dose-dependently attenuated by ET-2 to 250% of the control value. The effect of ET-2 was mimicked by the ETB-receptor agonist sarafotoxin S6c. The kinase inhibitor staurosporine (100 nmol/ liter) increased renin secretion and renin mRNA levels. Combination of staurosporine with forskolin produced the same effects on renin secretion and renin mRNA levels as did staurosporine alone. In the presence of both forskolin and staurosporine ET-2 had no significant effect on renin secretion and renin gene expression. The phorbol ester PMA (30 nmol/ liter), which was used to stimulate protein kinase C activity, attenuated cAMP stimulated renin secretion and renin mRNA levels. Lowering the extracellular concentration of calcium by the addition of 1 mmol/liter EGTA did not inhibit the effect of ET-2 on cAMP induced renin secretion and renin gene expression. These findings suggest that endothelins inhibit cAMP stimulated renin gene expression by an event that is mediated via ETB receptors. This inhibitory effect may in part involve protein kinase C activation.     

Glucose stimulates renin secretion via adrenergic mechanisms in the rat

To elucidate whether and why glucose directly influences renin secretion, the effect of glucose on renin secretion was investigated in the rat. In an in vivo study, renin activity significantly (p<0.01) increased from the basal value of 7.6 +/- 1.4 to 14.2 +/- 3.2 ng Ang I/ml/hr (mean +/- SD) after intravenous glucose (1.0 g/kg, in 50% glucose solution ) injection. Propranolol (10.5 mg/kg) pretreatment partly abolished the increase in renin activity induced by glucose injection. In an in vitro study, the isolated kidneys of male Wistar rats (200-250 g) were perfused with a basal perfusing medium containing 5.5 mM glucose for 20 min, and then perfused with the medium containing 16.5 mM glucose, 27.5 mM glucose, 5.5 mM glucose + 22 mM mannitol, 27.5 mM glucose + 1 microM phentolamine, or 27.5 mM glucose + 1 microM propranolol for 10 min, respectively. Renin activity was significantly increased from a basal value of 8.1 +/- 4.5 to peak value of 17.9 +/- 3.0 ng Ang I/ml/hr (p<0.01) by 16.5 mM glucose, to 59.0 +/- 10.5 ng Ang I/ml/hr (p<0.005) by 27.5 mM glucose, and to 24.7 +/- 5.8 ng Ang I/ml/hr (p<0.01) by 5.5 mM glucose + 22 mM mannitol. The increase in renin activity in the kidney perfused with 27.5 mM glucose was significantly (p<0.005) higher than that with 16.5 mM glucose or that with 5.5 mM glucose + 22 mM mannitol. The 27.5 mM glucose-stimulated increase in renin activity was not changed by the addition of 1 microM phentolamine, while it was completely abolished by the addition of 1 microM propranolol. These results suggest that glucose has a direct stimulating effect on renin secretion probably through beta-adrenergic mechanisms in the rat.     

Suppression of renin secretion in the isolated rat kidney by cycloheximide

Because 1,2:5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild akali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks. Thrombocytopenia was the dose-limiting toxicity. At a dose of 40 mg/m2/day for 5 days, the median platelet nadir was 31,000/mm3 and occurred on day 20; the plate count returned to normal within 8 days. At the same dose, the median white blood cell (WBC) nadir was 2,300/mm3 also on day 20-, the WBC count returned to normal within 7 days. Anemia, nausea, and vomiting were usually mild to moderate. No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified. Antitumor effects of DAG were observed in patients with renal, bladder, and small-cell lung cancers. An iv dose of 20-30 mg/m2/day for 5 consecutive days, repeated every 5-6 weeks, was recommended for phase II studies.     

Taurolithocholate can inhibit the biliary discharge of lysosomes in the rat

This report concerns a 66-year-old man with a melanocytoma arising at the foramen magnum. Magnetic resonance imaging disclosed a well-circumscribed tumor extending from the medulla oblongata to C1 with gadolinium enhancement. A heavily pigmented tumor located under the leptomeninges was removed surgically. Although the patient died 8 months later of renal cell carcinoma, no recurrence or metastasis of the melanocytoma was detected by radiographic examination. Microscopically, the resected tumor was composed of polygonal to spindle-shaped cells containing large amounts of melanin. The bland nuclei of the tumor cells were of uniform size. No mitotic figures were seen. The tumor cells were positively immunostained for S-100 protein and by antibody HMB-45. They were not stained using the Ki-67 (MIB-1) antibody, indicating low proliferative activity. The ultrastructural examination revealed numerous mature melanosomes and basal laminae surrounding nests of cells. The tumor was diagnosed as a melanocytoma on the bases of its microscopic features and the lack of Ki-67 immunoreactivity. The ultrastructural and immunohistochemical features of melanocytomas are distinct from those of meningiomas. It is likely that melanocytomas and melanotic schwannomas represent opposite extremes of the continuous spectrum of neuroectodermal tumors derived from the neural crest.     

Monoamine oxidase inhibitors inhibit [3H]quinpirole binding in rat striatal membranes

The paper deals with methods facilitating the preparation of oncospheres of the cestode, Hymenolepis diminuta, for experimental studies. Described in detail are procedures for the infection of the definitive hosts with the oncospheres; collection and artificial hatching of oncospheres; purification of hexacanths; preparation of extracts from the hexacanths; and preparation of hexacanths for electronmicroscopic studies.     

Genetic analysis of renin gene expression in rat adrenal gland

We examined the mechanism of the increased renin mRNA concentration in the adrenal glands of spontaneously hypertensive rats (SHR). In 52 female F2 rats (25 to 27 weeks of age) derived from SHR and Wistar-Kyoto rats, we determined blood pressure, renin mRNA concentration in the adrenal gland, plasma renin activity, plasma aldosterone concentration, and genotype of the renin gene. Eighteen of the F2 rats were fed a high salt (8%) diet for 14 days. The renin mRNA concentration in the adrenal glands showed a significant correlation with the genotype of the renin gene in the normal salt diet group (P <.0001), whereas this relationship was not observed in the high salt group. Multivariate analysis revealed that the plasma aldosterone concentration in the normal diet group was significantly explained (P=.0004, R2=.454) by plasma renin activity (P=.0005), the renin mRNA concentration in the adrenal gland (P=.0496), and the genotype of the renin gene (P=.0236). The SHR allele of the renin gene was associated with a lower aldosterone concentration. On the other hand, in the high salt diet group, only the genotype of the renin gene showed a significant relationship with plasma aldosterone concentration (P=.0237). Again, the SHR allele of the renin gene was associated with a lower aldosterone concentration. We can conclude that the higher renin mRNA concentration in the SHR adrenal glands is governed by the SHR allele of the renin gene or renin gene locus. The renin mRNA concentration in the adrenal gland exerts a minor influence on aldosterone synthesis. Paradoxically, the SHR allele of the renin gene or renin gene locus confers a lower rate of aldosterone synthesis at 25 to 27 weeks of age, the mechanism of which remains to be determined.     

Failure of heparin to inhibit the expression of the thrombin receptor following endothelial injury of the rabbit carotid artery

Rhythms of daily activity are found in all vertebrate species, some of them being diurnal (like humans, dogs, pigeons), others--nocturnal (like mice, rats and bats). Some species undergo very pronounced seasonal changes, as they hibernate in the winter or mate only at the specific seasons. The main regulator (a clock and a calendar) for daily and seasonal rhythms is the periodicity of the external light-darkness, reflected by the periodicity of melatonin secretion from the pineal gland, which is inhibited by light and induced during the darkness. In contrast to melatonin which peaks during the night both in diurnal and noctural species, the cyclicity of other hormones and several immune parameters correlates with the pattern of the animal locomotor activity-resting. The immune parameter that peaks at one time of day for a diurnal species peaks about 12 h later for a nocturnal one. Various immune parameters peak at various time points, anticipating an encounter with pathogens during the period of activity while energetically expensive resolution of the immune response during the resting. Daily and seasonal cyclicity of the immune functions are temporally integrated with other physiologic and behavioral processes and all of them are regulated and coordinated with daily and seasonal changes of an external environment by the neuroendocrine homeostatic system.     

Failure to replicate visceral learning in the acute curarized rat preparation.

Attempted to replicate a series of experiments reported to demonstrate robust visceral learning (autonomic instrumental learning) in rats during acute (2–4 hr) pharmacological paralysis. The results of exploratory procedures involving more than 2,000 animals are described, and 6 complete experiments are presented. In the 1st 3 experiments (with 72 male albino Sprague-Dawley rats), which closely followed the original procedures, the characteristics of the preparation were reproduced with the exception of initial heart rhythm and visceral learning. In the 2nd 3 experiments (with 74 male Sprague-Dawley rats), the respiration procedure was modified to satisfactorily reproduce the heart rhythm, and the PaO2, PaCO2, and pH, were verified to be within the range of freely moving, normally behaving Ss; nevertheless, visceral learning was not observed in these experiments either. It is concluded that the original visceral learning experiments are not replicable and that the existence of visceral learning remains unproven. However, neither the original experiments nor the replication attempt included the necessary controls to support a general negative conclusion about visceral learning. Possible explanations for a failure to replicate the original findings are discussed in terms of inadequate statistical power, unsatisfactorily reproduced experimental conditions, and spurious or artifactual results of the original experiments. (78 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Release of renin from glomeruli isolated from rat kidney

Cardiovascular and behavioural responses elicited by novel, noxious or aversive stimuli have been studied in dogs and cats. Hindlimb blood flow, heart rate and arterial blood pressure increased in dogs when an orienting response was elicited by a novel stimulus (a sound). Similar cardiovascular responses occurred in dogs to mild noxious stimulus and in cats displaying a threatening posture when confronted by a dog. The cardiovascular components of the orienting response to a sound habituated with repetition of the sound. In two dogs however sensitization (increase) of the response occurred with reped by repetition of the confrontations: the vasodilation in the muscles waned and eventually was replaced by vasoconstriction while the cardiac acceleration and pressor response persisted. The threatening response was the most persistent. The modification of the behavioural and cardiovascular aspect of the response was not developing in parallel. The cardiovascular pattern was altered before any apparent changes of the behavioural pattern occurred. The cardiovascular responses of the noxious stimulus in dogs and cardiovascular components of the defence reaction in cats were readily conditioned to a sound. The possible role of the modification of the cardiovascular pattern in defence reactions in pathogenesis of hypertension is discussed.     

Failure of the nonselective beta-blocker propranolol to affect lipoprotein lipase gene expression in the rat

Treatment with beta-blockers has been reported to be associated with the development of hypertriglyceridemia. The etiology, even the existence, of this phenomenon is controversial. The purpose of our study was to examine whether the nonselective beta-blocker propranolol causes hypertriglyceridemia in the rat and whether its action is mediated by the modulation of lipoprotein lipase (LPL) messenger RNA (mRNA) accumulation or activity. LPL activity was assayed in fresh tissue by incubation with tritiated triglycerides. LPL mRNA was quantified in total RNA by slot-blot analysis using a mouse LPL complementary DNA probe. We have conducted three series of experiments in unanaesthetized rats in order to study the effects of different single doses of propranolol (1.5 to 6 mg i.p.) and different durations of treatment (15 min to 4 wk). We measured triglyceride and cholesterol levels in plasma as well as the LPL activity and mRNA levels in the heart and adipose tissue before and after propranolol administration. In these experiments we did not find any significant decrease in either the activity or the amount of mRNA of lipoprotein lipase nor was there any change in plasma lipids following treatment. Our results lead us to the conclusion that the nonselective beta-blocker propranolol affects neither the activity nor the mRNA level of LPL in the rat.     

Effect of NaHCO3 on lactate kinetics in forearm muscles during leg exercise in man

We investigated NaHCO3 infusion effects on plasma lactate removal by forearm muscles and performance during intensive leg exercise. Seven subjects performed the force-velocity (FV) test with placebo and NaHCO3 (2 mEq.min-1) with a double-blind crossover protocol. Blood samples for arterial ([LA]A) and venous ([LA]V) lactate determinations were taken 1) at rest before infusion, and 2, 6, 10, 14, 18, and 22 min following its start; and 2) at the end of each exercise bout. The arteriovenous difference ([LA]A-V) was determined for each sampling. NaHCO3 significantly increased arterial bicarbonate concentration and pH during rest (P < 0.001; P < 0.001) and the FV test (P < 0.001; P < 0.05). During the test, [LA]A and [LA]V were significantly higher with NaHCO3 (P < 0.05, P < 0.001). At test onset, [LA]A-V became positive and increased until the braking force of 6 kg, with NaHCO3 and placebo, with values significantly lower for NaHCO3 (P < 0.001). Peak anaerobic power (Wanae, peak) and the corresponding braking force (Fmax) were also determined. Fmax was significantly increased with NaHCO3 (P < 0.001). In conclusion, the increasing rise in [LA]A and [LA]V induced by NaHCO3 may be partly explained by a decreased rate of lactate uptake by forearm skeletal muscles. NaHCO3 did not improve Wanae, peak, but improved Fmax, thus increasing FV duration.     

Integrins inhibit angiotensin II-induced contraction in rat aortic rings

Many extracellular matrix proteins contain the tripeptide sequence arginine-glycine-aspartate (RGD). This RGD motif is recognized by integrins, a family of adhesion receptors present on vascular smooth muscle cells. In the present study, we examined the ability of different RGD-containing peptides to affect the contraction of rat aortic rings in response to different agonists. We found that the peptide RGDS inhibited angiotensin-induced contraction in a dose dependent manner. In contrast, the peptides RGDW and RGES had no effect on angiotensin-induced contractility. We show that function-blocking antibodies to the integrins alphavbeta3 and alpha5beta1 also inhibit angiotensin-induced contraction. These effects were observed in the absence of an intact endothelium. In contrast, neither an antibody directed against the beta1 subunit nor the peptide RGDS had an effect on phenylephrine or 5-hydroxytryptamine-induced contraction. These data suggest that interactions of vascular smooth muscle with components of the surrounding extracellular matrix may influence the response of smooth muscle to agonists.