Glucose administration does not modulate prolactin response to exercise, TRH or haloperidol injection

Glucose was found to exert an In vitro regulatory effect on prolactin secretion. Its role in the modulation of stimulated secretion of prolactin in man is, however, not clear. To evaluate the effect of hyperglycaemia on prolactin release, three stimulatory tests with different mechanisms of stimulation were employed. Healthy male subjects served as volunteers during submaximal exercise, TRH test (0.2 mg i.v.) and administration of haloperidol (2 mg i.v.). Glucose (100 g in 400 ml) or an equal volume of water was given 30 min before the tests. Blood for glucose and prolactin analysis was taken via an indwelling catheter. The plasma prolactin concentration increased in response to each of the stimuli applied. However, the prolactin increase during hyperglycaemia did not differ from values obtained in tests performed in normoglycaemia after water administration. These results indicate that prolactin release in healthy man is not modulated by hyperglycaemia.     

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1 microliter and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mircogram/microliter) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/microliter) after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.     

Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides in male volunteers

STUDY OBJECTIVES: To test the effect of stellate ganglion block on tympanic membrane temperatures. DESIGN: Prospective, observational study. SETTING: Department of Anesthesia, Yamanashi Medical University, Yamanashi, Japan. SUBJECTS: 7 healthy male volunteers. INTERVENTIONS: Stellate ganglion block, 6 ml of 1% mepivacaine hydrochloride, was administered. MEASUREMENTS AND MAIN RESULTS: Application of temperature probes (right and left tympanic membranes, eight adhesive right skin-surface temperatures at the chest, upper arm, digital fingertip, lateral calf, thigh, and great toe) was followed by a 30-minute control period. Temperatures were recorded every 15 minutes for 30 minutes before stellate ganglion block and every 5 minutes for 40 minutes after the block. The right tympanic membrane temperature increased slightly but not significantly compared with the left tympanic membrane temperature 10 minutes after stellate ganglion block and subsequently. Right skin-surface temperature gradients at the upper limb decreased slightly but not significantly after stellate ganglion block. Similarly, right skin-surface temperature gradients at the lower limb decreased slightly but not significantly after stellate ganglion block. CONCLUSIONS: Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides.     

Depletion of cortical norepinephrine in rats by 6-hydroxydopamine does not impair performance of a delayed-nonmatching-to-sample task.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task, matched for performance, and randomly assigned to treatment with dorsal noradrenergic bundle injections of either 6-hydroxydopamine, to deplete cortical norepinephrine (NE), or vehicle, to control for the effects of surgery. After recovery, there were no significant differences between the groups when retrained on the DNMTS task at retention intervals (RIs) from 0.1 to 15.0 sec. Furthermore, no differences were observed when rats were trained at a 6.0-sec RI filled with distracting stimuli or when dummy information runs were added to increase proactive interference. These results demonstrate that depletion of cortical NE cannot account for the DNMTS performance deficits observed in rats recovered from pyrithiamine-induced thiamine deficiency (R. L. Knoth and R. G. Mair, 1991; J. K. Robinson and Mair, 1992). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

L-selectin (CD62L) blockade does not impair peritoneal neutrophil emigration or subcutaneous host defense to bacteria in rabbits

Neutrophil (PMN) recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. We explored the role of L-selectin (CD62L) in leukocyte emigration following instillation of bacteria into the peritoneum or s.c. skin in rabbits. Pretreatment with blocking mAb against L-selectin (LAM1.3) reduced peritoneal PMN emigration 4 h after i.p. inoculation with 10(10) CFU of Escherichia coli by only 17% compared with animals receiving a nonblocking L-selectin mAb (LAM1.14). Peritoneal PMNs from saline-treated rabbits demonstrated a complete absence of L-selectin, whereas those from LAM1.3-treated animals retained 43% of their baseline L-selectin expression. This suggests that L-selectin shedding is not a requisite event for PMN emigration under these conditions. In rabbits given s.c. inoculations with either Staphylococcus aureus or E coli, pretreatment with mAb LAM1.3 did not significantly impair PMN emigration at 24 h, nor increase the incidence, size, or associated mortality of resulting abscesses at 7 days compared with animals receiving nonblocking mAb LAM1.14. We conclude that: 1) mAb blockade of L-selectin in vivo only modestly affects acute, E. coli-induced peritoneal PMN emigration; and 2) L-selectin blockade does not increase infectious sequelae associated with s.c. bacterial inoculation. These findings of only mildly reduced PMN emigration into the peritoneum and no alteration in s.c. host defense differ from those reported with L-selectin blockade under other, nonbacterial inflammatory conditions, and suggest that redundant selectin-mediated mechanisms (P- and E-selectin) are sufficient for normal PMN emigration in response to bacterial stimulation.     

Phenylpropanolamine inhibits feeding, but not drinking, induced by hypothalamic stimulation.

Conducted 3 experiments using a total of 11 female Sherman rats. In Ss bearing lateral hypothalamic electrodes that elicited both feeding and drinking, ip injection of the appetite suppressant drug phenylpropanolamine (Propadrine) inhibited only feeding. This occurred whether feeding and drinking were tested simultaneously or separately. Selective inhibition of lateral hypothalamic feeding also followed injection of this drug through lateral, but not medial, hypothalamic electrode cannulas. It is concluded that hypothalamically induced feeding is under some of the same pharmacological controls as spontaneous feeding, that this control may be exerted, in part, in or near the lateral hypothalamus, and that the neural systems which induce feeding and drinking during hypothalamic stimulation can be pharmacologically separated. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interleukin-1 alpha-mediated promotion of long-term alloengraftment and short-term neutrophil expansion does not require the presence of either donor or host T cells

In earlier studies, we showed that a 14-day continuous subcutaneous infusion of recombinant human interleukin (IL)-1 accelerated neutrophil recovery and enhanced long-term chimerism in a bone marrow (BM) transplant model in which T-cell-depleted BALB/c donor BM was given to irradiated C57BL/6 fully allogeneic recipients. We have extended these studies to a model entirely devoid of donor and host T cells. In the model, donor BALB/c congenic severe combined immunodeficient (C.B-17-scid/scid) BM cells are T cell depleted. The cells are then transplanted into adult irradiated C57BL/6 hosts that have been thymectomized and treated with anti-CD4 and CD8. When IL-1 alpha was delivered subcutaneously using a mini-osmotic pump, it enhanced short-term neutrophil recovery and longer term alloengraftment despite the absence of T cells in the donors and the hosts. Therefore, T cells were not required for the promotional effects of IL-1 alpha on neutrophil recovery and alloengraftment. Studies also showed that the potency of the IL-1 alpha effects was related to the degree of donor cell engraftment, which was related to the irradiation dose and the presence of T cells. We conclude that IL-1 alpha can augment post-BM transplantation hematopoietic recovery and alloengraftment via a T-cell-independent mechanism by favoring donor allogeneic hematopoietic progenitor cell competition over limited numbers of host progenitor cells.     

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Previous studies show discrepancies concerning the effects of pretraining on spatial learning deficits induced by blockade of the N-methyl-d-aspartate (NMDA) receptor. These inconsistencies might be attributed to the differences in the nature of the pretraining tasks and the method of blocking NMDA receptors. In the present study, the authors pretrained rats in a spatial water maze task. The authors then trained them with a novel spatial task in a novel environment under chronic blockade of hippocampal NMDA receptors by intrahippocampal infusion of 2-amino-5-phosphonopentanoic acid (AP5) using osmotic pumps. Although the rats had acquired the basic techniques needed to solve a water-maze spatial task during pretraining, those given high or low doses of AP5 showed acquisition deficits. As the spatial pretraining failed to ameliorate the acquisition deficits of a new task in a novel environment, it was suggested that NMDA receptors were necessary in forming spatial representations. Because neither dose of AP5 affected the performance of a spatial task in the retention phase, sensory motor disturbances could not have caused these deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin

Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.     

Noise does not impair by masking: A reply to Poulton's "Composite model for human performance in continuous noise."

Contrary to E. C. Poulton (see record 1979-32826-001), it is argued that there is no evidence of noise-induced masking of articulatory or acoustic encoding in memory and that there is no evidence that noise impairs performance by masking the sound of the Ss' responses in serial reaction performance. Accordingly, Poulton's composite theory cannot be applied in the way he proposes. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of ejaculation induced by 8-OH-DPAT does not produce conditioned place preference in male rats.

The serotonin 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produces a drastic facilitation of ejaculation characterized by a significant reduction in the number of pre-ejaculatory intromissions and a shortening of ejaculation latency. In the present study, the authors evaluated whether this facilitation of ejaculation can induce a reward state assessed by conditioned place preference. Males treated with 0.1 or 1.0 mg/kg of 8-OH-DPAT showed a clear facilitation of ejaculation but did not develop conditioned place preference. These results clearly indicate that the pharmacological facilitation of ejaculation and the reduction of the number of intromissions does not necessarily make sex rewarding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhaled albuterol does not inhibit cellular influx or lung injury produced by segmental antigen challenge in humans

Many experimental protocols and published guidelines for performing bronchoscopy, bronchoalveolar lavage (BAL), bronchial biopsies, and segmental antigen challenge (SAC) of allergic asthmatic subjects recommend treating subjects with a beta-agonist prior to the procedure. However, the effect of beta-agonist pretreatment has not been reported. In a retrospective analysis of ragweed allergic subjects undergoing bronchoscopy, SAC, and BAL, we examined the effect of albuterol pretreatment on cellular influx and lung injury produced by antigen challenge. Forty-eight subjects, 17 who received no pretreatment and 31 who received four puffs of albuterol prior to bronchoscopy, comprised the study groups. No parameter monitored in BAL fluid 24 h after SAC (total cells, macrophages, neutrophils, eosinophils, lymphocytes, total protein, albumin, or eosinophil cationic protein) differed in subjects pretreated with albuterol when compared with subjects who were not pretreated. Although additional, prospective studies are warranted, we conclude that beta-agonist pretreatment of experimental subjects does not alter many aspects of the inflammatory response produced by SAC.     

The Th1 to Th2 shift induced by Schistosoma mansoni does not exacerbate murine aids (MAIDS)

Schistosoma mansoni infection in mice is associated with a switch from a Th1 to a Th2-type cytokine response. The role of Th1 and Th2 responses in immune dysregulations associated with AIDS and murine AIDS (MAIDS) is controversial, but a Th2 bias could be associated with disease progression, raising the hypothesis that helminth infections might accelerate the retroviral disease progression. Here, we used the murine model of AIDS to evaluate the course of the viral disease during co-infection with S. mansoni. C57BL/6 mice were infected with S. mansoni cercariae 8 weeks before intravenous challenge with the LP-BM5 retroviral complex. MAIDS did not progress faster in co-infected mice, in terms of spleen and inguinal lymphadenopathy size, ecotropic virus titres in the spleen, or in vitro proliferative responses to mitogen. Th2 cytokine production was not enhanced in co-infected animals, except for an isolated increase in IL-4 production 21 weeks after LP-BM5 infection. Co-infected animals had significantly lower lymph node and spleen weights than mice infected with LP-BM5 only. MAIDS did not influence the granulomatous response to S. mansoni in the liver of co-infected mice. Finally, infection with S. mansoni neither enhanced Th2 cytokine production nor accelerated MAIDS progression in animals subsequently challenged with LP-BM5.     

Cholesterol or triglyceride loading of human monocyte-derived macrophages by incubation with modified lipoproteins does not induce tissue factor expression

Macrophages/foam cells localized in cholesterol- and triglyceride-rich regions of atherosclerotic plaques express high levels of tissue factor (TF), the essential cofactor and receptor of factor VIIa. It is not clear whether modified lipoproteins, for which several agonistic effects on macrophages have been described, are independent stimuli of TF expression in these cells. Therefore, we studied the effect of short-term (1 day) and long-term (4 to 7 days) incubation of human monocyte-derived macrophages cultured in suspension with modified and native LDLs or VLDLs on the expression of TF mRNA, antigen, and activity. We used native LDL or VLDL, moderately oxidized LDL or VLDL, severely oxidized LDL or VLDL, acetylated LDL, and beta-VLDL at a protein concentration of 100 microg/mL. Cholesterol loading occurred within 9 hours after the addition of acetylated LDL and continued during long-term incubation. Incubation of severely oxidized LDL for 7 days resulted in a slight increase in cholesterol content. Triglyceride loading was observed during short-term and long-term incubation with native and modified VLDLs. Neither cholesterol nor triglyceride loading resulted in expression of TF. Bacterial LPS still could induce TF expression in lipid-laden macrophages. Our results show that incubation with modified lipoproteins or lipid loading does not lead to TF expression in monocyte-derived macrophages cultured in suspension. This suggests that induction of TF expression in foam cells in the atherosclerotic lesion is triggered by additional or other components.     

Terikalant, an inward-rectifier potassium channel blocker, does not abolish the cardioprotection induced by ischemic preconditioning in the rat

Recent results have shown that the sulfonylurea receptor couples to several types of inward-rectifier potassium (KIR) channels, which suggests that sensitivity to blockade of a pathophysiological phenomenon such as ischemic preconditioning (PC) by glibenclamide may not be the result of this compound selectively blocking the ATP-sensitive potassium (KATP) channel. Therefore, to address this possibility, a role for myocardial KIR v KATP channels in ischemic PC was evaluated in the rat. To test this hypothesis, anesthetized, open-chest, male Wistar rats were assigned to one of seven experimental protocols. Animals assigned to group I (control) received 30 min of occlusion and 2 h of reperfusion. Ischemic PC was produced by 3x5-min occlusion and 2-h reperfusion periods (group II). Terikalant (TK), an inward-rectifier potassium channel blocker, was used to test the role of other K+ channels, most notably the KIR, in the cardioprotective effect of ischemic PC in the rat. TK was given at a dose of 3 mg/kg, i.v., 15 min before the prolonged occlusion and reperfusion periods (group III). In groups IV, V, and VI terikalant (1, 3 and 6 mg/kg, i.v.) was given 15 min before ischemic PC (lowTK+PC, medTK+PC and hiTK+PC, respectively). Group VII consisted of glibenclamide (0.3 mg/kg, i.v.) given 30 min prior to ischemic PC (GLY+PC). Infarct size (IS) as a percent of the area at risk (AAR) was measured using the histochemical stain, 2,3, 5-triphenyltetrazolium chloride. The average IS/AAR for the control was 49.9+/-2.1%. Ischemic PC markedly reduced infarct size (8.6+/-1. 8%; * P<0.05 v control). Terikalant (TK; 1, 3 and 6 mg/kg, i.v.) did not abolish the cardioprotective effect of ischemic PC at any dose (15.5+/-6.4, 16.4+/-5.2 and 8.8+/-1.6%, respectively; * P<0.05 v control). TK itself had no effect on infarct size. GLY completely abolished the cardioprotective effect of ischemic PC (48.2+/-6.4%). In addition, the high dose of TK significantly (P<0.05) increased the action potential duration at 50% repolarization from 48+/-3 to 64+/-4 ms and 30 microM of TK, a concentration which produced a 39% decrease in the inward-rectifier potassium channel current in isolated guinea-pig ventricular myocytes in the whole-cell patch-clamp mode did not block the increase in K ATP current produced by the KATP opener bimakalim (3 microM). These results demonstrate that although the myocardial KATP channel belongs to the K IR superfamily, the endogenous myocardial KIR channel does not mediate ischemic PC in the rat heart; however, the K ATP channel does mediate its cardioprotective effect.     

Docosahexaenoic acid-rich fish oil does not enhance the elevation of serum transaminase and liver triacylglycerol induced by carbon tetrachloride in mice

Carbon tetrachloride (CCl4) is metabolized to trichloromethyl radical and induces liver injury with elevated serum transaminase and increased hepatic triacylglycerols (TG). To answer the question whether dietary polyunsaturated fatty acids (PUFA) enhance free radical-mediated liver injury, a docosahexaenoic acid (DHA)-rich fish oil (FO) or a saturated and monounsaturated fatty acid-rich beef tallow diet was fed to mice for 4 wk and then CCl4 was administered. When thiobarbituric acid-reactive substances (TBARS) were measured in the absence of antioxidant the FO diet and CCl4 treatment markedly increased liver TBARS values synergistically, apparently supporting the interpretation that the highly autoxidizable DHA accelerates lipid peroxidation induced by CCl4. However,no such marked interaction was observed between diet and CCl4 treatment in liver TBARS values measured in the presence of an antioxidant in the assay mixtures as well as in conjugated diene contents. Furthermore, the FO diet did not enhance CCl4-induced elevation of serum transaminase but lowered liver TG levels. The proportion of DHA,the most easily autoxidizable among common PUFA, was increased but those of eicosanoid precursors were decreased in liver phospholipids by CCl4 treatment, possibly reflecting the inflammation-related mobilization of eicosanoid precursors but not lipid peroxidation. These results indicate that dietary enrichment with DHA does not enhance CCl4-induced liver injury through the so-called free radical-mediated propagative autoxidation of DHA in mice.     

Expression of an activated erythropoietin or a colony-stimulating factor 1 receptor by pluripotent progenitors enhances colony formation but does not induce differentiation

Whether the presence of specific receptors on the surface of developing cells is the cause or consequence of lineage restriction is not known. If activation of specific receptors is the driving event in differentiation, the premature expression of specific receptors would promote differentiation along that pathway. In this study pluripotent progenitors, obtained from blast cell colonies (pooled or individual) of 5-fluorouracil-treated mice, were infected with retroviral vectors containing either an activated receptor for erythropoietin (EPO), an erythroid progenitor growth factor, or the receptor for colony-stimulating factor 1 (CSF-1), a macrophage growth factor. These receptors exhibit expression patterns restricted to committed progenitors. The developmental potential of infected pluripotent progenitors was not changed, although they expressed the exogenous genes, suggesting that in these cells activation of lineage-specific receptors does not induce differentiation. Acquisition of a constitutively activated EPO receptor allowed erythroid development in mixed colonies in the absence of EPO, as expected. Infection of progenitors with a virus containing the CSF-1 receptor promoted the development of granulocyte/macrophage (GM) colonies but did not alter the differentiation potential of either colony-forming unit (CFU)-GM or CFU-mix.     

Characteristic inhibition of in vitro swelling of purified rat liver mitochondria induced by Ca2+ or thyroxine by feeding rats a low casein diet

It has been shown previously by the author that the structure of rat liver mitochondria is changed by a low casein diet. In the present experiments, using the free fatty acid producing substances Ca2+ and thyroxine, and the free fatty acid sodium oleate, the influence of a 4% casein diet on the in vitro swelling process of purified rat liver mitochondria was investigated by following the decrease in optical density at 520 nm after addition of one of the swelling agents. Swelling due to hypotonicity was also investigated. Rats were fed the test diets for 80 to 100 days. Mitochondria were purified by washing three times; after each wash the isotonic suspension was centrifuged at 3,000 X g for 6 minutes. The results show that the in vitro swelling of mitochondria induced by Ca2+ or thyroxine was inhibited greatly in the early period of swelling in rats fed a low casein diet. By comparison to this, there was not a notable effect of a low casein diet on the rate of swelling induced by sodium oleate. But in the case of sodium oleate, the values of optical density were always higher in rats fed a low casein diet, and the differences between two groups were always significant. Swelling due to hypotonicity was not affected at all by a low casein diet.