Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in situ canine muscle

The mechanism(s) limiting muscle O2 uptake (VO2) kinetics was investigated in isolated canine gastrocnemius muscles (n = 7) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peak V(O2)). Two conditions were mainly compared: 1) spontaneous adjustment of blood flow (Q) [control, spontaneous Q (C Spont)]; and 2) pump-perfused Q, adjusted approximately 15 s before contractions at a constant level corresponding to the steady-state value during contractions in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2 Delivery, 1-2 ml/min of 10(-2) M adenosine were infused intra-arterially to prevent inordinate pressure increases with the elevated Q. The purpose of the study was to determine whether a faster adjustment of O2 delivery would affect V(O2) kinetics. Q was measured continuously; arterial (Ca(O2)) and popliteal venous (Cv(O2)) O2 contents were determined at rest and at 5- to 7-s intervals during contractions; O2 delivery was calculated as Q x Ca(O2), and V(O2) was calculated as Q x arteriovenous O2 content difference. Times to reach 63% of the difference between baseline and steady-state VO2 during contractions were 23.8 +/- 2.0 (SE) s in C Spont and 21.8 +/- 0.9 s in Fast O2 Delivery (not significant). In the present experimental model, elimination of any delay in O2 delivery during the rest-to-contraction transition did not affect muscle V(O2) kinetics, which suggests that this kinetics was mainly set by an intrinsic inertia of oxidative metabolism.     

Histamine-2-receptor blockade does not affect hyperemia after cerebral ischemia in young swine

Aldose reductase and aldehyde reductase were purified to homogeneity from multiple samples of human kidney cortex and medulla. A single form of aldose reductase is expressed in kidney that is kinetically and immunochemically indistinguishable from aldose reductase expressed in other human tissues. The results support the conclusion that there is a single human aldose reductase, and that aldose reductase is expressed in a reduced form, characterized by high sensitivity to aldose reductase inhibitors and ability to catalyze the reduction of glucose. Aldose reductase is easily oxidized to a form that is insensitive to aldose reductase inhibitors and unable to catalyze the reduction of glucose. This form does not appear to exist in vivo, even in kidney from diabetics. There is wide variation in the level of expression of aldose reductase in kidney, especially in cortex. The immunochemically separate but similar aldehyde reductase is also expressed in kidney as a single enzyme indistinguishable from aldehyde reductase from other human tissues. Aldehyde reductase levels exceed those of aldose reductase, both in cortex and medulla.     

L-NAME does not affect exercise-induced pulmonary hypertension in thoroughbred horses

The present study was carried out to examine the effects of nitric oxide synthase inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME) on the right atrial as well as on the pulmonary arterial, capillary, and venous blood pressures of horses during rest and exercise performed at maximal heart rate (HRmax). Experiments were carried out on seven healthy, sound, exercise-trained Thoroughbred horses. Using catheter-tip manometers, with signals referenced at the point of the shoulder, we determined phasic and mean right atrial and pulmonary vascular pressures in two sets of experiments [control (no medications) and L-NAME (20 mg/kg iv given 10 min before exercise studies)]. The studies were carried out in random order 7 days apart. Measurements were made at rest and during treadmill exercise performed on a 5% uphill grade at 6, 8, and 14.2 m/s. Exercise on a 5% uphill grade at 14.2 m/s elicited HRmax and could not be sustained for >90 s. In quietly standing horses, L-NAME administration caused a significant rise in right atrial, as well as pulmonary arterial, capillary, and venous pressures. This indicates that nitric oxide synthase inhibition modifies the basal pulmonary vasomotor tone. In both treatments, exercise caused progressive significant increments in right atrial and pulmonary vascular pressures, but the values recorded in the L-NAME study were not different from those in the control study. The extent of exercise-induced tachycardia was significantly decreased in the L-NAME study at 6 and 8 m/s but not at 14.2 m/s. Thus, L-NAME administration may not modify the equine pulmonary vascular tone during exercise at HRmax. However, as indicated by a significant reduction in heart rate, L-NAME seems to modify the sympathoneurohumoral response to submaximal exercise.     

Zinc status does not affect aluminum deposition in tissues of rats

To examine whether zinc deficiency would increase the toxicity of dietary aluminum, weanling, male Sprague-Dawley rats were fed purified diets containing either 2 or 30 mg Zn/kg diet, with or without 500 mg Al/kg diet for 28 d. Individually pair-fed rats were fed the 30 mg Zn/kg diet with or without added aluminum to control for inanition secondary to zinc deficiency. Rats fed the 2 micrograms Zn/kg diet showed evidence of zinc deficiency, including anorexia, growth retardation, and depressed concentrations of zinc in tibias and livers. Zinc deficiency did not significantly increase the concentrations of aluminum in the tibias, livers, kidneys, or regions of the brain examined (cerebrum, cerebellum, midbrain, and hippocampus). Inclusion of aluminum in the diet did not alter aluminum concentrations in the various tissues. Under the conditions of this study, zinc deficiency did not result in greater sensitivity to dietary aluminum exposure.     

Beta-2-agonists are still of value. Tolerance does not affect the bronchodilating effect

Use of the potent bronchodilators, beta 2-adrenoceptor agonists, has been a cornerstone of the treatment of obstructive lung disease, especially asthma, for the past 30 years. However, the occurrence of side effects and the development of tolerance have been discussed as limitations to their use. beta 2-Adrenoceptors are located on the surface of most cell types throughout the human body, and treatment with beta 2-agonists may exert effects in a wide variety of tissues. As with other pharmacological receptors, beta 2-adrenoceptors in most tissues develop tolerance as a result of continuous beta 2-stimulation. However, the bronchodilatory effect appears to be unaffected by the development of tolerance. Interestingly, most studies have yielded evidence suggesting tolerance development regarding protection against bronchoconstrictor stimuli such as methacholine, adenosine and exercise. Although the protective effect of a beta 2-agonist becomes attenuated with continuous treatment, this tolerance is partial and adequate residual protective effect remains.     

Psychological stress does not affect plasma catecholamines in subjects with cardiovascular disorder

Whereas the effects of cardiac transplantation on the catecholamine response to physical exercise have been studied previously, the impact on psychological stress is unknown. Here, the arterial catecholamine response to the Stroop test of patients with an orthotopic heart transplant (OHT) was compared with that in subjects who had received a coronary artery bypass graft (CABG) or who were in heart failure and destined for a heart transplant (HF). Subjects were tested whilst sitting and their usual drug therapy was maintained. The Stroop test increased subjects' subjective tension but did not affect arterial concentrations of adrenaline or noradrenaline in any group of subjects. Also, the concentration of both catecholamines was significantly higher in OHT and CABG subjects than in the HF group, but their relative concentration was unaffected by cardiovascular status or stress. It is concluded that the absolute concentrations of arterial catecholamines, but not their relative concentrations, depend on clinical status. Moreover, under these test conditions, subjects with a history of cardiovascular disorder do not show the normal catecholamine response to psychological stress.     

Oral arginine supplementation does not affect lymphocyte proliferation during endotoxin-induced inflammation in rats

Earlier studies from this laboratory were unable to confirm reported immunostimulatory effects of supplemental dietary arginine on healthy, unstressed young or aged rats. The present study was undertaken to determine effects of oral arginine supplementation on in vitro measures of immune function using a stressed rat model. The stressor used was intraperitoneal injection of bacterial lipopolysaccharide (1 mg/kg body wt). Four-month-old male Sprague-Dawley rats were placed in either a control or an arginine-supplemented (7.5 g/L arginine-HCl in drinking water) group for 7 d, after which control and supplemented rats received injections of endotoxin or phosphate-buffered saline. Rats were killed 3 d following injections. Endotoxin treatment resulted in lower food intake, less thymic cellularity and greater splenic weight. Endotoxin injections also enhanced proliferative response of rat splenocytes to pokeweed mitogen (1 mg/L) and lipopolysaccharide (25 and 100 mg/L) and enhanced response of thymocytes to concanavalin A (10 mg/L), phytohemagglutinin (25 and 100 mg/L) and pokeweed mitogen (1 mg/L). Supplemental arginine did not reduce thymic weight loss or influence mononuclear cell proliferation or interleukin-2 production in the presence or absence of endotoxin stress. These data indicate no benefit of arginine supplementation during endotoxin stress in rats.     

Flat affect in schizophrenia does not reflect diminished subjective experience of emotion.

Although accorded historical significance, affective features of schizophrenia have only begun to receive systematic empirical attention. Interestingly, both early psychopathology writers and more recent investigators have reported frequent discrepancies between schizophrenics' feelings and outward expressions of emotion. Using a more comprehensive assessment of emotion, the present study examines the relationship between emotional experience and expression in a sample of medication-free schizophrenics. Compared with their normal counterparts, schizophrenics were indeed much less facially expressive of both positive and negative emotions during emotion-eliciting films, yet they reported experiencing as much positive and negative emotion. Therefore, the blunted affect typical of some schizophrenics misrepresents their underlying emotional experience. Future research into an inhibition hypothesis is recommended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

滴定法测定冶金产品五氧化二钒中V_2O_3

经溶解、过滤、洗涤等条件及共存离子干扰影响等试验 ,提出测定五氧化二钒产品中三价钒量的容量法 ,结果满意。     

Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle

O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating a significant O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.     

Nitroglycerin does not alter pulmonary vascular permeability in isolated rabbit lungs

Nitroglycerin (NTG) produces vasodilation by releasing nitric oxide (NO) at the cellular level. Other studies have suggested that NO may directly alter vascular permeability and may alter the development of tissue injury. We therefore examined the effects of NTG on vascular permeability in the buffer-perfused rabbit lung under normal conditions and during lung injury. Vascular permeability was assessed by measurement of the capillary filtration coefficient (Kf,c). In normal lungs, NTG did not alter Kf,c or the rate of weight gain. Oxidant lung injury was produced by the addition of purine and xanthine oxidase and resulted in increased Kf,c and increased weight gain. However, NTG did not alter these effects of oxidant lung injury. We conclude that NTG does not alter pulmonary vascular permeability in either normal or oxidant-injured lungs.     

Catalase-free photosystem II: the O2-evolving complex does not dismutate hydrogen peroxide

A photosystem II (PSII) membrane-associated heme catalase has been identified as a major source of the dark H2O2-dismutation reaction in PSII membrane samples [Sheptovitsky, Y. G., and Brudvig, G. W. (1996) Biochemistry 35, 16255-16263]. Based on this finding, a catalase-free PSII membrane sample was prepared by using mild heat treatment to deplete most of the PSII membrane-associated heme catalase followed by inhibition of the residual catalase with 50 mM 3-amino-1,2,4-triazole, a specific heme catalase inhibitor that binds covalently to compound I. After these treatments, the PSII membrane sample exhibited only 0.02% of the original H2O2-dismutation activity when assayed in the presence of 20 mM 3-amino-1,2,4-triazole. This small residual H2O2-dismutation activity is attributed to adventitious metal ions or the non-heme iron in PSII because the activity was still present in a Mn-depleted PSII sample but was completely suppressed by adding 5 mM ferricyanide to the assay buffer; the effect of ferricyanide is attributed to oxidation of H2O2-dismutating cations. Although the H2O2-dismutation activity was completely eliminated by these treatments, the light-induced O2-evolution activity was retained. A single saturating flash given to catalase-free PSII membranes did not induce any H2O2-dismutation activity. These results demonstrate that the S1/S-1 and S2/S0 cycles of the O2-evolving complex of PSII do not occur in the presence of H2O2, as proposed by Velthuys, B., and Kok, B. [(1978) Biochim. Biophys. Acta 502, 211-221]. The light-induced O2-evolution activity in catalase-free PSII was found to be irreversibly impaired by micromolar concentrations of H2O2. Thus, it is possible that the PSII membrane-associated heme catalase plays an important role in protection of the O2-evolving complex from damage by H2O2.     

Angiotensin II receptor blockade in Syrian hamster (T0-2) cardiomyopathy does not affect microscopic cardiac material properties: implications for mechanisms of tissue remodeling

This study delineates the role of angiotensin II type I (AT1) receptor in the remodeling of Syrian cardiomyopathic hamsters. Twelve cardiomyopathic (T0-2) hamsters received L-158,809 treatment and libitum in their drinking water (27 micrograms/ml) and 9 cardiomyopathic and 9 normal FL-B hamsters received tap water from 1 to 4 months of age. Although pharmacologically effective with regard to complete suppression of the blood pressure response to angiotensin II infusion, L-158,809 did not diminish the progression or severity of cardiomyopathy. Heart weight/100 g body weight and left ventricular wall thickness adjusted for body weight of both L-158,809 and cardiomyopathic control hamsters did not differ and exceeded those of F1-B controls (p < 0.05). Myocardial material properties (e.g., stiffness and density) of cardiomyopathic hamsters treated with L-158,809 were not affected. Thus, the progression of fibrosis, calcification, and necrosis in T0-2 cardiomyopathic hamsters was not sensitive to AT1 receptor blockade.     

Long-term interferon-alpha therapy does not affect sex hormones in males with chronic hepatitis C

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.     

Recombinant bovine somatotropin (rbST) administration to creep-fed beef calves increases muscle mass but does not affect satellite cell number or concentration of myosin light chain-1f mRNA

Our objective in this study was to determine the effect of recombinant bovine somatotropin (rbST) on indices of muscle development in creep-fed beef calves. Crossbred steer calves were assigned to one of two treatment groups: control (sham-injected; n = 12) or rbST-treated (.09 mg x kg(-1) x d(-1); n = 12). Calves were injected every 14 d starting at d 28 of age and were weaned at 205 d of age. Supplemental creep feed was supplied free access to all calves to compensate for an expected increased protein and energy requirement in calves given rbST. Biopsy (d 100) and slaughter (d 206) samples of semitendinosus muscle were evaluated for satellite cell, myofiber nuclei numbers, and myosin light chain (MLC-1f) mRNA quantification. Myofiber nuclei and satellite cell numbers per 100 myofibers and MLC-1f mRNA:rRNA ratios at 100 and 206 d of age were not different (P > .10) between control and rbST-treated calves. Total gain, ADG, quality grade, femur length, percentage kidney, pelvic, and heart fat, dressing percentage, plasma IGF-I, and plasma urea nitrogen concentrations did not differ (P > .10) between control and rbST-treated calves. However, rbST-treated calves had larger longissimus muscle areas (P < .03), less marbling (P < .001), higher carcass conformation scores (P < .04), greater mass of separated muscle (P < .03), more ground meat (P < .01), and heavier carcass weights (P < .05) than control calves. Thus, rbST treatment increased muscle characteristics while nuclei number and MLC-1f mRNA concentrations remained the same, implying that the additional muscle growth was in a normal fashion.     

Leptin does not affect adipocyte glucose metabolism: studies in fresh and cultured adipocytes

Leptin, the 16-kd hormone produced by white fat cells, regulates energy homeostasis, satiety, and multiple sites in the neuroendocrine system. Leptin receptors have been identified in the central nervous system (CNS) and are widespread in peripheral tissues, including fat. Given the association between insulin resistance and obesity, it is important to establish whether leptin has additional effects on peripheral insulin action and glucose metabolism. This study examined whether leptin has a direct autocrine/paracrine action on glucose metabolism in both freshly isolated and 24-hour cultured rat fat cells. Freshly isolated rat adipocytes were incubated for 30 minutes with 200 ng/mL recombinant murine leptin. Thereafter, basal and insulin-stimulated (10(-8) mol/L) glucose transport, glycolysis-Krebs oxidation and lipogenesis ([6-14C]glucose conversion to [14C]O2 and to [14C]triglyceride), and lipolysis were measured. Upon leptin exposure, no statistical differences were detected in glucose transport or metabolism. Increasing the leptin concentration to 1 to 2 microg/mL or prolonging the duration of preincubation with the fat cells to 60 minutes before the metabolic assays did not alter the results. Finally, using two disparate fat cell culture methods with differing substrate additions (pyruvate and high or low glucose concentrations), there was no effect of 24-hour exposure to leptin (200 ng/mL) on basal and insulin-stimulated glucose transport or lipogenesis. We conclude that leptin does not modulate basal or insulin-stimulated glucose metabolism in isolated and cultured fat cells in vitro. However, in vivo, higher pericellular leptin concentrations, as well as other cellular or soluble serum factors, may exist that might lead to a physiologically relevant autocrine action of leptin.     

Bupropion improves attention but does not affect impulsive behavior in healthy young adults.

Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women) and 11 smokers (4 women) completed four 4-hr sessions where they received placebo, bupropion (150 or 300 mg), or d-amphetamine (20 mg) in capsules. Ninety minutes after capsule administration, participants were tested on attention with a simple reaction time task (SRT) and on impulsivity with the stop task, a delay and probability discounting task (DPD), and the balloon analogue risk task (BART). Participants also completed mood questionnaires during sessions. Bupropion (150 mg) decreased lapses in attention on the SRT, but did not affect performance on the stop task, DPD, or BART. Amphetamine decreased lapses in attention and speeded sensory motor processing time on the SRT but did not significantly affect responding on the stop task or DPD. On the BART, d-amphetamine tended to decrease risk taking in men but increased risk taking in women. Bupropion (300 mg) and d-amphetamine increased ratings of arousal. These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recombinant human interleukin-11 does not affect functions of purified human neutrophils in vitro

Recombinant human interleukin-11 (rHu-IL-11) is a multifunctional cytokine with thrombopoietic activity and demonstrated clinical efficacy in treating chemotherapy-induced thrombocytopenia. rHu-IL-11 also exhibits anti-inflammatory activity and is currently in clinical trials for the treatment of several inflammatory diseases. As neutrophils are involved in both innate immunity and an acute inflammatory response, the effect of rHU-IL-11 on the function of human peripheral blood neutrophils in vitro was examined. rHu-IL-11 was not cytotoxic and did not induce superoxide anion production or the release of granular enzymes from resting neutrophils. Phagocytosis and chemotaxis were unaffected. rHu-IL-11 treatment did not block the response of neutrophils to stimulation. Pretreatment with rHu-IL-11 did not reduce production of IL-8 following activation with lipopolysaccharide (LPS) or zymosan A particles. Pretreatment with rHu-IL-11 did not affect the release of lysozyme and beta-glucuronidase in response to A23187 or PMA-stimulated production of superoxide anion. These results indicate that rHu-IL-11 does not directly modulate key functions of neutrophils in vitro.