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At least 1,693 records · Page 94Linked to original sources
PubMed1995

Carvedilol, a new beta-adrenoreceptor blocker, vasodilator and free-radical scavenger, exerts an anti-shock and endothelial protective effect in rat splanchnic ischemia and reperfusion.

Splanchnic artery occlusion (SAO) followed by reperfusion results in circulatory shock in which oxygen-derived free radicals play an important role. Carvedilol, a novel beta adrenoceptor antagonist and a vasodilator, has been recently shown to exert potent antioxidant effects in multiple cell model systems. In the present experiment, we investigated the effect of carvedilol on SAO shock. Pentobarbital-anesthetized rats were subjected to 60 min of SAO followed by 120 min of reperfusion. Administration of 1 mg/kg carvedilol 10 min before reperfusion prolonged survival time (P < .05) and attenuated the increases in tissue myeloperoxidase activities (P < .01) and hematocrits (P < .001). Moreover, carvedilol significantly preserved superior mesenteric artery endothelial function (P < .01). Similar protection was seen in SAO shock rats treated with the superoxide free-radical scavenger superoxide dismutase. Except for a moderate attenuation of an increase in hematocrits, protective effects were not seen in SAO shock rats treated with the prototypic beta blocker propranolol. These results indicate that in murine SAO shock, carvedilol affords significant protection, which may be achieved through maintenance of tissue blood perfusion, quenching of oxygen free radicals, preservation of vascular endothelial function, and inhibition of neutrophil-endothelial interaction and its resultant increased microvascular permeability.

Adrenergic beta-Antagonists↗
PubMed1994

Human insulin-like growth factor I exerts hematopoietic growth-promoting effects after in vivo administration.

Recombinant human insulin-like growth factor I (rhIGF-I) was administered to mice to determine its effect on hematopoiesis. Mice given intraperitoneal (IP) injections of 5 micrograms rhIGF-I for 7 days exhibited a significant increase in bone marrow (BM) hematopoietic progenitor cells, suggesting that rhIGF-I acts as a hematopoietic growth factor. Treatment with rhIGF-I also resulted in increases in erythroid precursor cells. Mice were then placed on azidothymidine (AZT), which produces significant myelotoxic effects. Splenic and BM progenitor cell content and hematocrit values were all significantly increased if rhIGF-I (5 micrograms injected IP every day for 28 days) was concurrently administered with AZT. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of rhIGF-I resulted in an increase in hematopoietic progenitor cell content. No significant pathologic effects or weight changes were observed in mice receiving repeated injections of rhIGF-I at this dose and schedule. Thus, rhIGF-I exerts hematopoietic growth-promoting effects in vivo and may be of potential clinical use in promoting hematopoiesis in the face of myelotoxic therapy.

Animals↗
PubMed1994

Brugia malayi in Mastomys natalensis: influence of immunostimulators on exertion of antifilarial activity of diethylcarbamazine.

The effect of immunopotentiators (Freund's complete adjuvant and CDRI Compound no. 84/201) has been evaluated on exertion of antifilarial activity of diethylcarbamazine (DEC) at different dose levels in Mastomys natalensis experimentally infected with Brugia malayi. DEC alone exhibited dose dependent micro- as well as macrofilarial action. In combination with immunomodulators, activity of DEC was significantly enhanced even at a lower dose level (12.5 mg/kg). However at higher dose level (> 25 mg/kg) of the drug along with immunostimulator the adulticidal activity was significantly reduced. Nevertheless, immunopotentiators themselves displayed certain amount of antifilarial action (34-38% macrofilaricidal).

Adjuvants, Immunologic↗
PubMed1993

50 Hz AC sinusoidal electric fields do not exert genotoxic effects (micronucleus formation) in human lymphocytes.

Electromagnetic fields produce a variety of effects in several biological systems, including human peripheral blood lymphocytes. A great concern exists regarding possible carcinogenic effects in subjects exposed environmentally to such fields in the vicinity of power lines and electric domestic appliances. Using human lymphocytes from 33 healthy donors and a sensitive cytogenetic method, the cytokinesis-block micronucleus assay, we have demonstrated that the exposure to 50-Hz AC sinusoidal electric fields over a wide range of intensities (0.5-10 kV/m in air) does not increase the spontaneous frequency of micronuclei. Moreover, these fields did not affect the mitomycin-C-induced micronucleus formation, suggesting that they did not exert any synergistic or antagonistic effect.

Adult↗
PubMed1993

Droperidol exerts dual effects on repolarization and induces early afterdepolarizations and triggered activity in rabbit Purkinje fibers.

This study was designed to clarify discrepancies concerning the effects of droperidol on cardiac repolarization. Myocardial electrical activity was recorded by using microelectrode technique in rabbit Purkinje fibers and guinea pig ventricular muscle. In Purkinje fibers stimulated at 60 pulses/min, low concentrations (0.01-0.3 microM) of droperidol increased in a dose-dependent fashion action potential duration (APD) without altering the other parameters. At 1 and 3 microM, droperidol led to the reversal of the prolonging effect. The highest concentrations used (10 and 30 microM), produced shortening in APD at 50% repolarization concomitantly with a significant decrease in Vmax, action potential amplitude and resting membrane potential. Inexcitability occurred in 4 of 15 preparations exposed to 30 microM. In 8 of 15 Purkinje fibers, the prolonging effect induced by low concentrations was so important that APD exceeded the 1000-msec period of basal stimulation and early afterdepolarizations (EADs) and triggered activity developed. In guinea pig ventricular muscle, these effects were notably less pronounced. Prolongation of action potential showed a reverse use-dependence (i.e., much greater at the lowest stimulation frequencies), whereas Vmax depression was use-dependent. Decreasing extracellular K concentration from 4.0 to 2.7 mM enhanced the incidence of EADs in Purkinje fibers, whereas elevating the K concentration from 2.7 to 5.4 mM abolished them completely and shortened drastically APD. EADs were also eliminated by increasing magnesium concentration from 1 to 5 mM. Addition of isoproterenol favored EADs, whereas these were suppressed at plateau level by exposure to 0.3 microM nifedipine. The results indicate that in rabbit Purkinje fibers, droperidol exerts a dual effect on repolarization, prolongation with low concentrations with development of EADs and subsequent triggered activity. These abnormalities were suppressed at high concentrations concomitantly with a marked depression of other characteristics. These observations suggest multiple ionic channel activities and further studies are required to precise the underlying mechanisms at channel level.

Action Potentials↗
PubMed1993

Tauroursodeoxycholate and tauro-beta-muricholate exert cytoprotection by reducing intrahepatocyte taurochenodeoxycholate content.

Cytoprotection by tauroursodeoxycholic acid and tauro-beta-muricholic acid against taurochenodeoxycholic acid-induced toxicity was examined with reference to intracellular bile acid content in primary cultured rat hepatocytes. In comparison with levels in the group administered taurochenodeoxycholic acid 1 mmol/L alone, lactate dehydrogenase levels in the culture medium decreased significantly in groups simultaneously administered taurochenodeoxycholic acid 1 mmol/L and tauroursodeoxycholic acid 0.5 to 2 mmol/L or tauro-beta-muricholic acid. Results of the trypan blue uptake test indicated that the lactate dehydrogenase release was indeed caused by cell damage. After the administration of tauroursodeoxycholic acid 2 mmol/L or tauro-beta-muricholic acid 2 mmol/L, intracellular taurochenodeoxycholic acid content was consistently reduced to half of that after administration of taurochenodeoxycholic acid alone. Simultaneous administration of dibutyl cyclic AMP also reduced intracellular taurochenodeoxycholic acid content and lactate dehydrogenase release. Being rinsed with tauroursodeoxycholic acid and tauro-beta-muricholic acid after being precultured in taurochenodeoxycholic acid 1 mmol/L also markedly reduced their taurochenodeoxycholic acid content. Taurocholic acid caused limited reduction of intracellular taurochenodeoxycholic acid but not suppression of lactate dehydrogenase release. Taurodehydrocholic acid showed no reduction of taurochenodeoxycholic acid content and no decrease of lactate dehydrogenase release. Although only small amounts of tauroursodeoxycholic acid or tauro-beta-muricholic acid were found to accumulate in hepatocytes, taurocholic acid increased as if replacing taurochenodeoxycholic acid. The results suggest that tauroursodeoxycholic acid or tauro-beta-muricholic acid may exert cytoprotective effects by lowering intracellular taurochenodeoxycholic acid levels associated with their optimal hydrophilicity.

Animals↗
PubMed1993

Potent intracellular oxidative stress exerted by the carcinogen 4-nitroquinoline-N-oxide.

Oxidative stress exerted by superoxide-generating (redox-cycling) agents such as paraquat triggers the soxRS regulon of Escherichia coli. In this system, SoxR protein is the redox-sensitive activator of the soxS gene, the product of which then activates the approximately 10 promoters of this regulon. We found that 4-nitroquinoline-N-oxide (4NQO) is a powerful inducer of soxS, > 10-fold more potent than paraquat. The transcriptional induction of the soxS gene by 4NQO was tightly dependent on a functional soxR gene and on the presence of molecular oxygen, as found previously for several well characterized redox-cycling agents. Two 4NQO-related compounds were also shown to induce soxS:4-nitropyridine-N-oxide, with an efficiency only slightly less than 4NQO, and 4-hydroxyaminoquinoline-N-oxide, at approximately 50-fold lower potency than 4NQO. E. coli strains that are hypersensitive to oxidative stress (owing to deficiency in either superoxide dismutases or oxidative DNA repair enzymes) were hypersensitive to killing by 4NQO. Thus, considerable oxidative stress is induced in cells by 4NQO, which might contribute to the carcinogenic potency of this compound.

4-Nitroquinoline-1-oxide↗
PubMed1993

A three-year follow-up of 195 reported occupational over-exertion injuries.

Three years after reporting occupational over-exertion injuries, 181 persons took part in a follow-up study by questionnaire. The objective was to study these persons with respect to their current status of health, well-being and functional capacity and when possible compare collected data to reference data from the "normal population". The studied group reported more physical and psychological symptoms than the reference groups. More than 50% reported difficulties in activities of daily living. Long sick-leaves in the year following the reported injury were associated with remaining pain and low rate of employment. Three years after the injury, 109 persons were in employment. Almost one third of these had changed occupations and now had more varied tasks than at the time of the report. Those whose work loads had been reduced after the injury, did not report less musculoskeletal disorders than others. However, access to social support was positively related with health and psychological well-being.

Activities of Daily Living↗
PubMedDate not supplied

NK cells from mammary tumor bearing mice do not exert natural killer activity but function as antibody dependent cellular cytotoxicity effectors.

We have previously found that natural killer (NK) activity is profoundly decreased in BALB/c mice bearing large mammary tumors. Kinetic studies showed that after 14 days of tumor implantation a reduction of 25-40% of NK cytotoxicity can be observed and by 21 days only very low levels of NK reactivity can be detected in the spleens of tumor bearers. Phenotypic analyses of the splenic NK cells of tumor bearing mice revealed that they have similar density, granularity and comparable levels of NK 2.1 antigen on their surfaces as compared to NK cells from normal mice. However, in tumor bearers there was a shift from a high surface asialo GM1-bearing NK population to low-density surface asialo GM1-positive bearing cells. Phenotypically characterized NK cells were quantitated to test the possibility that splenic NK cells from tumor bearers migrated to other organs and were therefore at lower levels in the spleen. No significant differences were observed in the percentages of NK cells from spleens from normal and tumor bearing mice. Using single cell conjugate assays it was found that there was no impairment in the capacity of NK from tumor bearers to bind the NK-sensitive Yac-1 cells, however, this event did not result in lysis of the target cells. To elucidate whether the lytic machinery of the tumor bearers' NK cells was inactivated, their capacity to effect antibody dependent cellular cytotoxicity (ADCC) was evaluated. In contrast to the results observed when NK activity was evaluated, NK cells from tumor bearing mice exerted higher levels of ADCC than their normal counterparts and they had a higher expression of Fc receptors on their surfaces. These results suggest that the depression of NK activity observed in tumor bearing mice occurs at a triggering step that is not necessary for the activation of the NK effectors via the Fc receptor and that no major impairment of the lytic machinery occurs during mammary tumorigenesis.

Animals↗
PubMed1996

Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension.

Acute changes of heart rate variability (HRV) depict alterations in autonomic influences on cardiovascular system and often precede ventricular arrhythmias. The aim of the study was to assess effects of sublingual 10 mg nifedipine (n = 15) or 25 mg captopril (n = 13) on HRV in consecutive patients admitted to hospital due to severe hypertension. HRV was calculated on-line from 300 cardiac cycles before and 60-90 min after drug administration. At baseline systolic blood pressure (SBP) was > 190 mm Hg and/or diastolic blood pressure (DBP) > 110 mm Hg. Both agents caused similar reduction of blood pressure (BP). Nifedipine reduced variance (-63 +/- 6%; P < 0.0001) and high-frequency (HF) component (-72 +/- 8%; P < 0.0001), and increased both LF/HF ratio (+870 +/- 336%; P < 0.02) and heart rate (+14 +/- 3%; P < 0.0001). Captopril exerted different effects: variance and HF component increased by +176 +/- 55%; (P < 0.007) and +126 +/- 44% (P < 0.015), respectively. LF/HF (low/high frequency) ratio decreased (-44 +/- 19%; P < 0.04) together with heart rate (-4 +/- 1%; < 0.009). It is concluded that captopril, in contrast to nifedipine, increases HRV and decreases LF/HF ratio and therefore is a better choice in hypertensive patients who might be prone to dangerous arrhythmias.

Acute Disease↗
PubMed1996

Gonadal steroids exert facilitating and "buffering" effects on glucocorticoid-mediated transcriptional regulation of corticotropin-releasing hormone and corticosteroid receptor genes in rat brain.

Gonadal steroids profoundly influence several brain functions and are apparently responsible for gender-specific differences in the regulation of hypothalamic-pituitary-adrenal (HPA) secretions. In this study, we examined the so-called "activational" effects of gonadal steroids on the glucocorticoid-mediated regulation of the gene transcription of corticotropin-releasing hormone (CRH) and corticosteroid receptors in brain areas of relevance for the control of pituitary-adrenal secretion. The efficacy of adrenalectomy (ADX) and chronic treatment with high doses of corticosterone (B) to regulate the gene transcription of CRH and corticosteroid receptors in the hypothalamic paraventricular nucleus (PVN) and hippocampus was studied in male and female rats under the conditions of deprivation of gonadectomy (GDX) and replacement with different gonadal steroids, such as estradiol (E2), progesterone (P), and dihydrotestosterone (DHT). In both sexes, ADX alone or in combination with GDX increased, and B treatment suppressed, the steady-state levels of CRH and corticosteroid receptor mRNAs, whereas GDX alone failed to affect any of the parameters studied. Administration of gonadal hormones to steroid-deprived (ADX/GDX) animals partially attenuated the upregulation of mRNAs encoding corticosteroid receptors in the hippocampus. Supplementation with gonadal steroids modified the effects of B on the gene transcription of CRH and corticosteroid receptors. Whereas P alone or in combination with E2 counteracted the B-induced downregulation of GR and CRH gene transcription in females, DHT and E2 administration further potentiated the effects of B on these parameters in a sex-specific manner. Taken together, the results indicate that gonadal steroids have minor influence on MR, GR, and CRH gene transcription under basal conditions, exert "glucocorticoid-like" effects on the transcription of corticosteroid receptors in the hippocampus of steroid-deprived animals, and interact with glucocorticoid-mediated mechanisms of regulation in the HPA axis through gender-specific "buffering" and "potentiating" effects.

Adrenal Glands↗
PubMed1996

A miniswine model of acute exertional heat exhaustion.

METHOD: We examined the thermoregulatory and hemodynamic responses of 12 miniswine (31 +/- 3.9 kg) during 25-30 min of treadmill exercise (5.4 km.h-1, 5% grade) under cool (10 degrees C), moderate (20 degrees C) and warm (30 degrees C) ambient temperature (Ta) conditions. RESULTS: Within 15-20 min of exercise at Ta = 30 degrees C, the miniswine demonstrated significant hyperventilation, hypersalivation, and unsteady gait. Exercise-heat endurance time (T) at Ta = 30 degrees C decreased by 35% and 40% in comparison to T at Ta = 20 degrees C and 10 degrees C, respectively. This resulted from a significant rise in heat strain (S)-defined as the rate of change in rectal temperature. Averaged throughout exercise, S increased from 0.04 +/- 0.01 degree C.min-1 and 0.05 +/- 0.02 degree C.min-1 at Ta = 10 degrees C and 20 degrees C, respectively, to 0.10 +/- 0.03 degree C.min-1 at Ta = 30 degrees C. Due to the comparatively large storage capacity of the porcine spleen relative to humans, splenectomized miniswine were used. This permitted calculation of percentage changes in plasma volume (% delta PVc) from hematocrit (HCT) and hemoglobin (HGB) without the confounding effects of splenic red cells released into the circulation during exercise. Independent of Ta, pre-exercise PVc decreased 3%-5% (p < or = 0.05) within the first 10 min of exercise, but increased 5%-9% (p < or = 0.05) by 10 min post-exercise. CONCLUSION: We conclude that the poor thermoregulatory ability of miniswine manifested in insignificant sweating and restricted evaporative cooling, may make them an appropriate model for acute exertional heat exhaustion in humans working in hot, humid conditions and/or wearing impermeable protective clothing. Further, evaluation of plasma volume changes from HCT and HGB in a miniswine model should consider the merit of a splenectomized design.

Animals↗
PubMed1995

Factors affecting the ability of the renal medulla to exert an antihypertensive function.

To examine whether changes in renomedullary osmolality and the activity of the renin-angiotensin system may influence the ability of the renal medulla to exert an antihypertensive function, rats were exposed to several manoeuvers. These affected either the medullary osmolality or the renin-angiotensin system (salt or saccharose load, salt depletion, treatment with captopril alone or in combination with salt depletion). A comparison of the antihypertensive capacity of the renal medulla was studied by transplanting renal medullae from the various groups into one-kidney one-clip hypertensive rats. A significant and quantitatively similar reduction in blood pressure was observed in hypertensive rats that received transplants of the medullae from control, salt or saccharose loaded rats and captopril treated rats. In contrast, medullae from salt depleted rats did not affect blood pressure when transplanted into hypertensive animals. The addition of captopril restored the antihypertensive function of renal medulla in salt depleted rats. The results do not support the view that osmolality of the renal medulla regulates its antihypertensive capacity, and suggest that angiotensin II may restrain renomedullary antihypertensive function.

Animals↗
PubMed1995

Glycosylation improves the priming effect exerted by recombinant human granulocyte colony-stimulating factor (lenograstim) on human neutrophil superoxide production.

The role of glycosylation in modulating the activity of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on polymorphonuclear leukocytes (PMNs) was investigated. We addressed this study by comparing the effects of lenograstim (glycosylated rHuG-CSF) and its deglycosylated counterpart on superoxide production by PMNs on fibronectin. When the triggering activity of the cytokine was evaluated, no O2- release was elicited from neutrophils treated with either preparation of rHuG-CSF. Instead, a clear potentiation of both fMLP- and TNF-induced respiratory burst was produced by preincubating the cells with rHuG-CSF. Such effect was found to be significantly increased when glycosylated versus deglycosylated preparation was used, leading to the conclusion that the sugar moiety of the molecule could be of importance in improving the priming activity exerted by rHuG-CSF on PMN metabolic response.

Drug Synergism↗
PubMed1996

Rehabilitation of ten soldiers with exertional rhabdomyolysis.

This case study describes the rehabilitation of 10 active duty U.S. soldiers with exertional rhabdomyolysis. The pathophysiology of rhabdomyolysis is discussed. The initial management is concerned with accurate diagnosis and monitoring of laboratory values to prevent complications. Active and passive range of motion, strength, and induration were used as indicators of recovery. The goal of rehabilitation was to safely return patients to their basic training units without activity restrictions as quickly as possible. All 10 soldiers were able to pass the Army Physical Fitness Test at the end of their training cycle. For those patients with rhabdomyolysis who desire to return to a high level of function, close monitoring of exercise intensity appears to allow for a safe, expedient return to previous levels of function. This description of a rare disorder will increase awareness and stimulate discussion so that more specific guidelines for rehabilitation can be developed.

Adolescent↗
PubMed1996

Sudden exertional death in a soldier with sickle cell trait.

Most family physicians regard sickle cell trait (SCT) as a benign condition. But in special circumstances SCT can have deadly consequences. SCT affects 8% of the black population. Most of the cases of sudden exertional death (SED) in those with SCT have occurred during military basic training. A retrospective review of all soldiers in basic training found that those with SCT had a 40-fold increased risk of SED. This paper discusses an individual case of SED that occurred at Fort Sill, Oklahoma. A literature review makes comparisons to our index case. The current Army Medical Corps recommendations for prevention of SED as well as the current military SCT screening policy will be discussed. Prospective studies are needed to evaluate the efficacy of the currently recommended preventative guidelines as well as to more fully evaluate the potential for SCT to cause significant morbidity and mortality during military basic training.

Adult↗
PubMed1996

Rational design of a new C-myristylamido peptide exerting potent and selective PKC inhibitory activity.

A 3D model of the catalytic domain of PKC was built based on the X-ray structure of the homologous PKA enzyme. The two enzymes were found to have similar general architecture although differing for the number of negatively charged clusters and their location near the phosphorylation site. These differences were consistent with the charge requirements deduced from the consensus sequence of PKC and PKA substrates. A Myristyl Binding Site (MBS) was found in the PKC model between helix C and sheets 8 and 9. The identification of this MBS allowed the rationalization of the results obtained with N-myristoylated peptide inhibitors and, above all, the design of ITF1671 (H-RFARKGALRQKN-CONH-Myr), a new C-myristylamido peptide, which exerted one of the most potent inhibitory activity against PKC and PKM known to-date.

Animals↗
PubMed1996

Exertional heat illness in Marine Corps recruit training.

BACKGROUND: Exertional heat illness (EHI) is a recurring problem in military training resulting in loss of manpower and training effectiveness. A scientific approach to this problem requires quantitative analysis of factors related to its occurrence. METHODS: Review of clinic and hospital records identified all cases of EHI occurring among 217,000 Marine Corps recruits (90% male, 80% age 18-20 yr) entering 12-week basic training at Parris Island, SC during 1982-1991. RESULTS: There were 1454 cases, 89% males and 11% females; 11% of male and no female cases were hospitalized. The majority (88%) of cases occurred during May-September, with a peak rate of 2% of recruits in summer. Most of the cases occurred during the cooler early morning hours when recruits performed strenuous exercise. During 0700-0900 hours the rate of heat casualties increased substantially as the Wet Bulb Globe Temperature Index (WBGT) increased, beginning at levels as low as 65 degrees F. EHI rates increased 26- and 39-fold at WBGT 75- < 80 degrees F (over baseline rates at < 65 degrees F) for immediate and prior day exposures, respectively. Exposure to WBGT of 80 + degrees F was infrequent (25%) among the early morning cases at the time of illness, while it was common (87%) on the day prior to illness, suggesting a lasting effect of heat exposure. CONCLUSIONS: Risk for EHI in military training increases markedly as WBGT levels rise above 65 degrees F; cases occur primarily with strenuous exercise (e.g., running); and heat stress exposure on prior days may be important.

Adolescent↗