共查询到20条相似文献,搜索用时 15 毫秒
1.
This study shows that acute exercise in healthy subjects is a modest oxidative stress, which may be related to an increase in antioxidant activity and down-regulation of nitric oxide formation. 相似文献
2.
1. We studied the effect of ketotifen, a second generation H1-receptor antagonist on nitric oxide synthase (NOS) activity in colonic mucosa and in renal tissues, and on rat renal haemodynamics in vivo. 2. Ketotifen (100 micrograms ml-1) increased human colonic NOS activity from 3.7 +/- 0.6 to 14.5 +/- 1.3 nmol g-1 min-1 (P < 0.005, ANOVA). In rat renal cortical and medullary tissues ketotifen increased NOS activity by 55% and 86%, respectively (P < 0.001). The stimulation of NOS activity was attenuated by NADPH deletion and by the addition of N omega nitro-L-arginine methyl ester (L-NAME) or aminoguanidine, but not by [Ca2+] deprivation. NOS activity was unaffected by two other H1-antagonists, diphenhydramine and astemizole, or by the structurally related cyproheptadine. Renal cortical NOS activity was also significantly stimulated 90 min after intravenous administration of ketotifen to anaesthetized rats. 3. Ketotifen administration to anaesthetized rats induced modest declines in blood pressure and reduced total renal, cortical and outer medullary vascular resistance. This is in contrast to diphenhydramine, which did not induce renal vasodilatation. 4. We conclude that ketotifen stimulates NOS activity by mechanisms other than H1-receptor antagonism. The association of this effect with therapeutic characteristics of ketotifen and the clinical implications of these findings are yet to be defined. 相似文献
3.
Z Zhang D Naughton PG Winyard N Benjamin DR Blake MC Symons 《Canadian Metallurgical Quarterly》1998,249(3):767-772
The effects of substrate, L-Arg and cofactors, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (H4B) and calmodulin (CaM), on chiral discrimination by rat neuronal nitric oxide synthase (nNOS) for binding the enantiomers of 1-(1-naphthyl)ethylamine (ligand I), 1-cyclohexylethylamine (ligand II), and 1-(4-pyridyl)ethanol (ligand III) were studied under anaerobic conditions by optical absorption spectroscopy. The ratio of the dissociation constant (Kd) values for the S- and R-enantiomers of ligand I (S/R) was 30, while the S/R ratio for ligand II and the R/S ratio for ligand III were 1.8 and < 0.14, respectively, in the presence of 0.15 microM H4B. However, in the presence of 1 mM L-Arg, the S/R ratio of the Kd values for ligand I was decreased down to 5.9. In the presence of both 1 mM L-Arg and 0.1 mM H4B, the S/R ratios for ligands I and II and the R/S ratio for ligand III were enormously increased up to 29, > 80, and 60, respectively. These and other spectral observations strongly suggest that strict chiral recognition at the active site of nNOS during catalysis is exhibited only in the presence of the active effector. 相似文献
4.
Because of the increasing incidence of tuberculosis consequent on the increasing number of patients with drug-related or HIV-induced immunosuppression, the problems of the invasive or noninvasive treatment of osteoarticular tuberculosis have come up again. While the approach aimed at the elimination of infectious foci with an adequate combination of medical therapy with a conservative treatment or surgery is still valid, the advanced technology of osteosynthesis systems and prosthetic replacement for spinal, hip and knee involvement respectively, with suitable indications, affords new solutions of surgical technique. The objective is to achieve surgical procedures that preserve at best the physiology of locomotor apparatus. 相似文献
5.
JB Gordon GA Moreira DC O'Donnell AM Aldinger ML Tod 《Canadian Metallurgical Quarterly》1997,42(6):738-743
Effective attenuation of pulmonary vasoconstriction is essential during early postnatal development when increased pulmonary vascular resistance (PVR) may lead to a resumption of right-to-left shunting across fetal channels. In addition, modulation of venous resistance contributes to normal lung fluid balance. This study was designed to identify the relative modulating effects of endothelium-derived nitric oxide (EDNO) and dilator prostaglandins (PG) on normoxic and hypoxic pulmonary vasomotor tone in young newborns. Total and segmental PVR were measured using inflow-outflow and double occlusion techniques in isolated lungs of 6-h-old lambs studied under control conditions or after blocking PG and/or EDNO synthesis with indomethacin and/or N omega-nitro-L-arginine, respectively. During normoxia, both indomethacin and N omega-nitro-L-arginine were required to increase total PVR, but EDNO appeared to have the greater modulating effect. Indomethacin markedly enhanced hypoxic pulmonary vasoconstriction of large and small arteries and small veins, whereas N omega-nitro-L-arginine caused a lesser, but significant, increase in hypoxic pulmonary vasoconstriction of small arteries and veins, suggesting that dilator PG played the dominant modulating role during hypoxia. In addition, PG synthesis appeared to be enhanced after inhibition of EDNO synthesis. In contrast, indomethacin caused a decrease in venous resistance, suggesting that constrictor prostanoids had a greater effect than dilator PG on this segment. EDNO had a modest modulating effect on venous resistance in these lungs. These data suggest that dilator PG and EDNO exert complementary effects in attenuating total and segmental PVR during normoxia and hypoxia in 6-hold lamb lungs. 相似文献
6.
RB Stevens DE Sutherland JD Ansite M Saxena TJ Rossini BK Levay-Young BJ Hering CD Mills 《Canadian Metallurgical Quarterly》1997,159(11):5329-5335
Evidence in this paper indicates that insulin can down-regulate the inducible nitric oxide synthase (iNOS) pathway in vivo. The iNOS pathway is up-regulated in diabetes-prone rats and mice and is associated with an autoimmune process. However, the results presented here indicate that macrophage nitric oxide (NO) production and iNOS mRNA expression are also elevated in rats or mice made diabetic by streptozotocin injection in which there is no primary autoimmune component. Insulin administration reduces NO production in autoimmune-prone and streptozotocin-induced diabetic rodents. Finally, insulin decreases macrophage NO production in normal hosts. These results indicate that the autoimmune paradigm is inadequate to explain increased NO in diabetes. As a potential mechanism to explain insulin-mediated regulation of NO production, TGF-1 may be involved because 1) macrophages from diabetic mice produce less TGF-beta1 than macrophages from normal hosts; 2) the circulating TGF-beta1 level is lower in diabetic mice; and 3) insulin administration increases circulating TGF-beta1 in normal mice. Together, these results provide evidence that increased NO in diabetes is not only a cause but also an effect of beta-cell destruction and results in part from a heretofore unrecognized immunomodulatory activity of insulin. 相似文献
7.
Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it. 相似文献
8.
I Yokoi Y Namba H Kabuto K Inada M Iida A Mori N Ogawa 《Canadian Metallurgical Quarterly》1996,21(10):1187-1192
2,3,5-Trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504), an inhibitor of 5-lipoxygenase and thromboxane A2 synthase and a scavenger of active oxygen species, has been shown to exhibit profound anti-tumour activity against three established murine adenocarcinomas (MACs) that are generally refractory to standard cytotoxic agents. For the cachexia-inducing MAC16 tumour, optimal anti-tumour activity was seen at dose levels of 10 and 25 mg kg-1 day-1, together with a reversal of cachexia and a doubling of the time to sacrifice of the animals through cachexia from 8 days to 17 days. The remaining tumour fragments showed extensive necrosis in regions distal from the blood supply. Growth of the MAC13 tumour was also effectively suppressed at dose levels between 5 and 50 mg kg-1 day-1, resulting in a specific growth delay between 1.0 and 1.2. Growth of the MAC26 tumour was also inhibited a concentration-related manner, with doses of 25-50 mg kg-1 day-1 being optimal. Anti-tumour activity towards all three tumours at low dose levels of CV-6504 was effectively suppressed by concurrent administration of linoleic acid (1 g kg-1 day-1), suggesting that inhibition of linoleate metabolism was responsible for the anti-tumour effect. Tumour sensitivity may be correlated with increased DT-diaphorase that are required to metabolise CV-6504 to the active hydroquinone, which inhibits 5-lipoxygenase activity. 相似文献
9.
JA Romand MR Pinsky L Firestone HA Zar JR Lancaster 《Canadian Metallurgical Quarterly》1994,76(3):1356-1362
Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. We studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial beta-adrenergic blockade (propranolol, 0.15 mg/kg i.v.) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa (from 19.8 +/- 6.1 to 28.3 +/- 8.7 mmHg, P < 0.01) and calculated PVR (from 437 +/- 139 to 720 +/- 264 dyn.s.cm-5, P < 0.01), both of which decreased with 17 ppm NO. ALI decreased arterial PO2 and increased airway pressure, shunt, and dead space ventilation. Ppa (19.8 +/- 6.1 vs. 23.4 +/- 7.7 mmHg) and PVR (437 +/- 139 vs. 695 +/- 359 dyn.s.cm-5, P < 0.05) were greater during ALI than during hyperoxia. No inhalation had no measureable effect during ALI before or after beta-adrenergic blockade. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 micrograms) induced an immediate decrease in Ppa and PVR during ALI.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
10.
Y Numagami AB Zubrow OP Mishra M Delivoria-Papadopoulos 《Canadian Metallurgical Quarterly》1997,69(4):1542-1547
Nitric oxide (NO) is reported to cause neuronal damage through various mechanisms. The present study tests the hypothesis that NO synthase inhibition by N(omega)-nitro-L-arginine (NNLA) will result in decreased oxygen-derived free radical production leading to the preservation of cell membrane structure and function during cerebral hypoxia. Ten newborn piglets were pretreated with NNLA (40 mg/kg); five were subjected to hypoxia, whereas the other five were maintained with normoxia. An additional 10 piglets without NNLA treatment underwent the same conditions. Hypoxia was induced with a lowered FiO2 and documented biochemically by decreased cerebral ATP and phosphocreatine levels. Free radicals were detected by using electron spin resonance spectroscopy with a spin trapping technique. Results demonstrated that free radicals, corresponding to alkoxyl radicals, were induced by hypoxia but were inhibited by pretreatment with NNLA before inducing hypoxia. NNLA also inhibited hypoxia-induced generation of conjugated dienes, products of lipid peroxidation. Na+,K+-ATPase activity, an index of cellular membrane function, decreased following hypoxia but was preserved by pretreatment with NNLA. These data demonstrate that during hypoxia NO generates free radicals via peroxynitrite production, presumably causing lipid peroxidation and membrane dysfunction. These results suggest that NO is a potentially limiting factor in the peroxynitrite-mediated lipid peroxidation resulting in membrane injury. 相似文献
11.
JA Youssef DW Thibeault MH Rezaiekhaligh SM Mabry MI Norberg WE Truog 《Canadian Metallurgical Quarterly》1999,75(3):199-209
This study was undertaken to examine the combined effect of nitric oxide (NO) and hyperoxia on lung edema and Na,K-ATPase expression. Newborn piglets were exposed to room air (FiO2 = 0.21), room air plus 50 ppm NO, hyperoxia (FiO2 >/= 0.96) or to hyperoxia plus 50 ppm NO for 4-5 days. Animals exposed to NO in room air experienced only a slight decrease in Na,K-ATPase alpha subunit protein level. Hyperoxia, in the absence of NO, induced both the mRNA and the protein level of Na,K-ATP-ase alpha subunit and significantly increased wet lung weight, extravascular lung water, and alveolar permeability. NO in hyperoxia decreased the hyperoxic-mediated induction of Na,K-ATPase alpha subunit mRNA and protein while wet lung weight, extravascular lung water, and alveolar permeability remained elevated. These results suggest that 50 ppm of inhaled NO may not improve hyperoxic-induced lung injury and may interfere with the expression of Na,K-ATPase which constitutes a part of the cellular defense mechanism against oxygen toxicity. 相似文献
12.
Changes in nitric oxide (NO) concentration and cerebral blood flow (CBF) in the parietal cortex during hypercapnoea were investigated in anaesthetized rats, using a NO-selective electrode and laser Doppler flowmetry. When hypercapnoea was induced by inhalation of 5% CO2 for 10 min, both the NO concentration and CBF increased. After administration of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, both the basal NO and CBF decreased, and responses to hypercapnoea were also significantly suppressed by 70.1% and 73.2%, respectively, compared with the control state. These results suggest that NO derived from nNOS is involved not only in maintaining resting cerebral circulation but also in regulating CBF response during hypercapnoea. 相似文献
13.
We observed clinical response to inhaled nitric oxide (iNO) in 12 neonates with persistent pulmonary hypertension of the newborn (PPHN). Clinical response was defined as a decrease in oxygenation index (OI) by 40%. Ten of 12 neonates had response to iNO showing decrease OI from 46.1+/-7.6 to 14.4+/-6.8 at 1 hour after inhalation. Sustained improvement of OI was achieved in 8 neonates and two neonates were relapsed. In the group of neonates who had OI above 40 (n=7), 6 of them showed the decrease of OI from 66.1+/-4.8 to 18.3+/-8.0 at 1 hour. In two groups, one had OI of 40 or greater, and the other OI of 40 or less, there were no differences in pattern of response and early death rate. The response rates according to underlying diseases were as follows; idiopathic PPHN 100%, respiratory distress syndrome 100%, and diaphragmatic hernia 66.7%. Relapse was observed in one neonate with sepsis caused by pneumonia and in one infant with meconium aspiration syndrome. Two infants showed no response to iNO (one diaphragmatic hernia and one suspected pulmonary hypoplasia). We conclude that iNO therapy could improve oxygenation in high percentage of newborn infants with severe PPHN of various underlying conditions except pulmonary hypoplasia. 相似文献
14.
PM Hellstr?m A al-Saffar T Ljung E Theodorsson 《Canadian Metallurgical Quarterly》1997,42(8):1640-1651
The lipopolysaccharide (endotoxin) of gram-negative bacteria has systemic effects in animals and man. Our aim was to investigate the effects of E. coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyze plasma and tissue concentrations of intestinal neuropeptides. When lipopolysaccharide (20-160 micrograms/kg) was administered intravenously, the migrating myoelectric complex was replaced by spike bursts accompanied by rapid transit. Tissue concentrations of substance P and neurokinin A decreased, while plasma levels of calcitonin gene-related peptide increased N omega-Nitro-L-arginine, N omega-L-arginine methyl ester, dexamethasone, or indomethacin prevented these changes in myoelectric activity and tissue contents of neuropeptides. All of these compounds, except indomethacin, prevented the increased rate of transit. Thus, lipopolysaccharide changes motility through the nitric oxide and arachidonic pathways, resulting in rapid transit through the gut. 相似文献
15.
BACKGROUND: There has been some controversy regarding the effect that a long labor can have on fetal well-being. This study was undertaken to evaluate the effect of duration of labor both the first and second stage on the acid-base variables in the umbilical artery of the newborn. METHODS: Bloodsampling was attempted from all infants born at our department between October 1994 and September 1995. Nineteen hundred and forty-one live infants were delivered during the period. Sampling was unsuccessful in 264 cases and after excluding infants with operative delivery, multiple gestations, breech presentation, prematurity, postmaturity and infants small for gestational age 1255 remained singleton, term infants with vertex presentation and non-operative vaginal birth. RESULTS: We found no correlation between duration of the first stage of labor and neither pH nor base excess in umbilical artery blood. There was a significant correlation between duration of the second stage of labor and both the pH and base excess. For vaginal nulliparas we found that pH=7.30-0.016 x second stage duration in hours and base excess=-3.71-0.692 x second stage duration in hours. For women with previous vaginal births pH=7.31-0.029 x second stage duration in hours and base excess=-2.38-1.306 x second stage duration in hours. CONCLUSIONS: We find no correlation between duration of the first stage of labor and umbilical artery pH or base excess. We do find a correlation between duration of the second stage of labor and the umbilical artery pH and base excess. However, a prolongation of the second stage with as much as three hours would give an expected lowering of the umbilical artery pH with only 0.05 and of base excess with 2.1 mmol/l for vaginal nulliparas and correspondingly with 0.09 and 3.9 mmol/l in women with previous vaginal births. This effect on pH and base excess is so small that it is hardly clinically relevant and we do not find any support for the belief that a long labor -- in the absence of other risk factors -- is to the disadvantage of the fetus. 相似文献
16.
R Nowak TM Murphy DR Lindsay P Alster R Andersson K Uvn?s-Moberg 《Canadian Metallurgical Quarterly》1997,62(4):681-688
Lambs develop a preferential relationship with their mothers within 24 h after birth. In a first experiment, we attempted to determine whether neonatal sucking was a potent reinforcer in the establishment of this preference by temporarily covering the udders of ewes after parturition. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking either between birth and 6 h afterward (group 2) or between 12 and 18 h after birth (group 3). Measurements of cholecystokinin plasma levels at birth and at 6 and 18 h showed that all lambs ingested some colostrum when the udder was made accessible. When tested in a two-choice test situation at 24 h of age, lambs from group 1 spent significantly more time near their mothers than near the alien ewes, those from group 2 did not show any discrimination, and lambs from group 3 clearly preferred the alien ewes. At 2 days of age, lambs from groups 1 and 3 showed a strong preference for their mothers, whereas those from group 2 still displayed no preference. In a second experiment, we attempted to determine whether sucking also had a reinforcing value in the maintenance of this preference. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking for 6 h either at birth (group 2) or at the age of 3 days (group 3). Lambs from group 2 did not discriminate between their own and alien dams when tested at 24 h of age, unlike those of groups 1 and 3. When a second test was performed at 4 days of age, all the lambs showed a strong preference for their dams. We concluded that sucking has strong rewarding properties in the establishment of a preferential relationship with the mother by the lamb. On the other hand, the maintenance of this preference does not rely on sucking as strongly. 相似文献
17.
18.
1. Respiratory frequency, shivering, ear skin temperatures and rectal temperatures were observed following intraventricular injections of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and saline (NaCl) into new-born lambs exposed to ambient temperatures of 4, 21, or 30 degrees C. 2. Intraventricular NA caused respiratory rate to decrease and body temperature to increase in the 30 degrees C environment. At 21 degrees C, it increased ear skin temperature but did not significantly affect rectal temperature. At 4 degrees C, NA decreased shivering and rectal temperature fell. 3. 5-HT elevated respiratory rate in the 30 degrees C environment and increased ear skin temperature in the 21 and 4 degrees C environments. In the 4 degrees C environment rectal temperature decreased. 4. In general, the change in rectal temperature was related to the dosage of drug administered. Control injections of NaCl had no significant effect on any of the variables measured. 5. The monoaminergic pathways involved in thermoregulation in the new-born lamb appear to be organized in a manner similar to that of the adult sheep and are functional at birth. 相似文献
19.
Effects of the oral or intraperitoneal administration of an Enterococcus preparation, FK-23, to mice on the interferon (IFN) production by their spleen cells and on the host defense against the infection with herpes simplex virus (HSV)-1 were examined. Spleen cells were obtained from the mice intraperitoneally treated with cyclophosphamide (CY) and subsequently orally administered FK-23 preparation, and then cultured with phytohemagglutinin-P or bacterial lipopolysaccharide in vitro. They produced higher titers IFN than those obtained from control mice which were not treated with the FK-23 preparation. The IFN activity was neutralized mainly by antiIFN-beta antibody. Correspondingly, oral (5 mg/mouse) or intraperitoneal (1 mg/mouse) administration of the FK-23 preparation protected some of the CY-pretreated mice from death by HSV-1 infection. 相似文献
20.
Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide 总被引:2,自引:0,他引:2
There has been confusion as to what role(s) nitric oxide (NO) has in different physiological and pathophysiological mechanisms. Some studies imply that NO has cytotoxic properties and is the genesis of numerous diseases and degenerative states, whereas other reports suggest that NO prevents injurious conditions from developing and promotes events which return tissue to homeostasis. The primary determinant(s) of how NO affects biological systems centers on its chemistry. The chemistry of NO in biological systems is extensive and complex. To simplify this discussion, we have formulated the "chemical biology of NO" to describe the pertinent chemical reactions under specific biological conditions. The chemical biology of NO is divided into two major categories, direct and indirect. Direct effects are defined as those reactions fast enough to occur between NO and specific biological molecules. Indirect effects do not involve NO, but rather are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. RNOS formed from NO can mediate either nitrosative or oxidative stress. This report discusses various aspects of the chemical biology of NO relating to biological molecules such as guanylate cyclase, cytochrome P450, nitric oxide synthase, catalase, and DNA and explores the potential roles of NO in different biological events. Also, the implications of different chemical reactions of NO with cellular processes such as mitochondrial respiration, metal homeostasis, and lipid metabolism are discussed. Finally, a discussion of the chemical biology of NO in different cytotoxic mechanisms is presented. 相似文献