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Peroxynitrite, a cytotoxic oxidant formed in the reaction of superoxide and nitric oxide is known to cause programmed cell death. However, the mechanisms of peroxynitrite-induced apoptosis are poorly defined. The present study was designed to characterize the molecular mechanisms by which peroxynitrite induces apoptosis in HL-60 cells, with special emphasis on the role of caspases. Peroxynitrite induced the activation of apopain/caspase-3, but not ICE/caspase-1 as measured by the cleavage of fluorogenic peptides. Considering the short half-life of peroxynitrite and the kinetics of caspase-3 activation (starting 3-4 h after peroxynitrite treatment), the enzyme is not likely to become activated directly by the oxidant. Caspase-3 activation proved to be essential for DNA fragmentation, because pretreatment of the cells with the specific tetrapeptide inhibitor DEVD-fmk completely blocked peroxynitrite-induced DNA fragmentation. Peroxynitrite-induced cytotoxicity was also significantly altered by the inhibition of caspase-3, whereas phosphatidylserine exposure was unaffected by DEVD-fmk treatment. Because many of the effects of peroxynitrite are mediated by poly(ADP-ribose) synthetase (PARS) activation, we have also investigated the effect of PARS-inhibition on peroxynitrite-induced apoptosis. We have found that PARS-inhibition modulates peroxynitrite-induced apoptotic DNA fragmentation in the HL-60 cells. The effect of the PARS inhibitors, 3-aminobenzamide and 5-iodo-6-amino-1,2-benzopyrone were dependent on the concentration of peroxynitrite used. While PARS-inhibition resulted in increased DNA-fragmentation at low doses (15 microM) of peroxynitrite, a decreased DNA-fragmentation was found at high doses (60 microM) of peroxynitrite. PARS inhibition negatively affected viability as determined by flow cytometry. These data demonstrate the crucial role of caspase-3 in mediating apoptotic DNA fragmentation in HL-60 cells exposed to peroxynitrite.  相似文献   

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Studied the effects of prolonged exposure to 2 noise stressors (random and patterned intermittent 0 and 85 db) on the performance of 60 male undergraduates on 3 tasks requiring different abilities (reaction time, rate control, and time-sharing). The sensitivity of alternate metrics of performance degradation was also evaluated within an analysis of covariance design. Ss were randomly assigned to the various treatments, and a series of 2 * 2 * 4 (Noise Intensity * Noise Quality * Trial Blocks) covariance analyses were carried out. The effects of random noise on performance depended on the type of task and performance measure. The reaction-time task was affected, the rate-control task was not, and the time-sharing task was affected only after continued exposure to noise. Patterned noise had insignificant effects. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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OBJECTIVE: The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. RESEARCH DESIGN AND METHODS: Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. RESULTS: The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak. CONCLUSIONS: It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.  相似文献   

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The synthesis of (+/-)-1-ethylenedioxy-trans-2-(beta-R,S-hydroxypropyl)-3-(beta-acetoxyethyl)cyclopentane (IV), starting from (+/-)-1-ethylenedioxy-trans-2-propargyl-3-(beta-hydroxyethyl)cyclopentane (I) by indirect hydration with mercuric acetate and hydrogen sulphide, is reported.  相似文献   

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Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first- and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic glucose clamp. Twelve healthy male subjects, age (mean +/- SEM) 22.5 +/- 0.5 years, body mass index (BMI) 21.7 +/- 0.6 kgm-2, were studied in a randomized, double-blind study design. Glibenclamide 10 mg or placebo was taken before a 4-h hyperglycaemic clamp (blood glucose 8 mmol L-1 during the first 2 h and 32 mmol L-1 during the next 2 h). During hyperglycaemic clamp at 8 mmol L-1, the areas under the delta insulin curve (AUC delta insulin, mean +/- SEM) from 0 to 10 min (first phase) were not different: 1007 +/- 235 vs. 1059 +/- 261 pmol L-1 x 10 min (with and without glibenclamide, P = 0.81). However, glibenclamide led to a significantly larger increase in AUC delta insulin from 30 to 120 min (second phase): 16087 +/- 4489 vs. 7107 +/- 1533 pmol L-1 x 90 min (with and without glibenclamide respectively, P < 0.03). The same was true for AUC delta C-peptide no difference from 0 to 10 min but a significantly higher AUC delta C-peptide from 30 to 120 min on the glibenclamide day (P < 0.01). The M/I ratio (mean glucose infusion rate divided by mean plasma insulin concentration) from 60 to 120 min, a measure of insulin sensitivity, did not change: 0.26 +/- 0.05 vs. 0.22 +/- 0.03 mumol kg-1 min-1 pmol L-1 (with and without glibenclamide, P = 0.64). During hyperglycaemic clamp at 32 mmol L-1, the AUC delta insulin from 120 to 130 min (first phase) was not different on both study days: 2411 +/- 640 vs. 3193 +/- 866 pmol L-1 x 10 min (with and without glibenclamide, P = 0.29). AUC delta insulin from 150 to 240 min (second phase) also showed no difference: 59623 +/- 8735 vs. 77389 +/- 15161 pmol L-1 x 90 min (with and without glibenclamide, P = 0.24). AUC delta C-peptide from 120 to 130 min and from 150 to 240 min were slightly lower on the glibenclamide study day (both P < 0.04). The M/I ratio from 180 to 240 min did not change: 0.24 +/- 0.04 vs. 0.30 +/- 0.07 mumol kg-1 min-1 pmol L-1 (with and without glibenclamide, P = 0.25). In conclusion, glibenclamide increases second-phase insulin secretion only at a submaximally stimulating blood glucose level without enhancement of first-phase insulin release and has no additive effect on insulin secretion at maximally stimulating blood glucose levels. Glibenclamide did not change insulin sensitivity in this acute experiment.  相似文献   

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There has been in recent literature some evidence indicating that intermittent sound as opposed to steady sound sources has a more disturbing effect on Ss. This paper includes those studies which have appeared since 1950 and indicates that high intensity or intermittent sound generally produces symptoms of discomfort, instability, and distraction. In addition decrements in performance may be related to the level of the sound as well as its intermittency. Changes in blood pressure, respiration, EEG, pulse rate, etc., as a result of sound have been reported in some studies. Some theoretical issues are included in the discussion. 80 refs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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A method based on discounted income and risk assessment was developed to aid in the selection of dairy sires. The discounted profit generated from milk production of daughters was proposed as the suitable composite selection criterion to combine estimates of predicted transmitting ability (PTA) for yields of milk, fat, and protein and estimates of sire evaluations for dystocia or expected progeny difference. Steps are described to derive discounted profit (defined as expected income) for a sire with known PTA and evaluation for dystocia. The derivation of profit considered costs for semen, dystocia, heifer raising, production and maintenance of the daughter, and income from milk. Variance of income from a sire depended on the reliability of his PTA and evaluation for dystocia. Total variance from a selected set of sires was defined as the risk. A quadratic programming procedure was developed to identify the best set of sires from a given pool of sires that met a desired expected income goal with minimum risk. Combinations of sires with minimum risk for all possible levels of expected income were defined by the expected income variance frontier. The set of sires at the maximum lower boundary for 95% confidence of the expected income variance frontier was defined as the optimum set of sires to be selected; the optimum set maximized the 95% guaranteed expected income. The quadratic programming procedure provided the optimum percentage of cows to be mated to each sire in the selected set.  相似文献   

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In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.  相似文献   

11.
The study of the coagulation in rats fed with a balanced diet, including 12% of different animal or vegetable fats, during 6 months, shows that the time of coagulation in rats receiving one of the following oils: palm, sunflower, Canbra, is significantly higher than the ones fed with butter. On the other hand, the coagulation time observed in the groups is correlated with the oleic acid level in the corresponding diet. The results obtained here may lead to important practical applications.  相似文献   

12.
This study investigated a possible relationship between exercise intensity and mood alteration that commonly is associated with physical activity. 91 college students completed the Profile of Mood States before and after 20 min. of jogging at three intensities: 55%, 75%, and 79% of age-adjusted maximum heart rate on different occasions. Exercisers also completed a demographic inventory, a Lie Scale, and the State-Trait Anxiety Inventory. Contrary to our expectations, the interaction between exercise intensity and pre-post mood benefits was not significant. Supporting the manipulation of exercise intensity, the univariate interaction between exercise intensity and pre-post exercise scores on Fatigue was significant. Joggers reported short-term mood benefits on the combined subscales of the Profile of Mood States, and each subscale contributed to the benefits. Thus, regardless of the low- or moderate-intensity, participants reported that they "felt better" after exercising.  相似文献   

13.
The presence of HIV-1 DNA sequence variants of pediatric AIDS patients was investigated in a two-stage polymerase chain reaction (PCR) using nested primers for the first and second (V1-V2) hypervariable regions of the proviral envelope (gp 120) gene (env1). Gel electrophoresis analysis yielded amplified DNA bands which exhibited length variations which were characteristic for each child. The PCR products were cloned and the resulting clones demonstrated inserts of different lengths in a patient and between patients. Analysis of five clones from two different patients at the level of DNA sequencing indicates an extreme heterogeneity in the V1-V2 region. DNA maximum similarity between all of the isolated clones ranged between 69 to 96%. Comparison between DNA sequences of the isolated clones and HIV-1 strains of other parts of the world was also performed. The highest percentage of similarity that was found with known HIV variants included the following strains: HIVADA, HIVJFL, HIVSW42, HIVSWB83, HIVTRA2, HIVWMJ22. The sequences also showed a high degree of similarity to the clade B virus HIVSF162. The analyzed HIV-1 sequences demonstrated the expected high degree of variation in the V1-V2 region of the envelope gene and in some cases that the variation between isolates from the same patient may exceed the variation between the individual clones and the reference HIV-1 strains.  相似文献   

14.
STUDY OBJECTIVE: To discriminate the effects of body fat reduction on improvements in peak aerobic capacity made following exercise training during cardiac rehabilitation. DESIGN: Observational, prospective study. SETTING: Outpatient cardiovascular health center at regional academic center. PATIENT INTERVENTIONS: Peak oxygen uptake (pkVO2), percent body fat, lean body mass (LBM), and other anthropometric measures were assessed before and after a 3-month program of cardiac rehabilitation and exercise training in 500 consecutive cardiac patients following a major coronary event. Baseline pkVO2 was corrected for LBM (pk/VO2 lean) and compared with posttraining values. RESULTS: Following exercise training, percent body fat decreased 5% from 26.2+/-8.0 to 24.8+/-7.5 (p<0.0001), and LBM increased 1% from 61.3+/-12.5 to 61.7+/-11.8 kg (p=0.02). pk/VO2 increased 16% from 16.0+/-4.1 to 18.5+/-4.8 mL/kg/min (p<0.0001), and pkVO2 lean increased 13% from 21.7+/-5.3 to 24.6+/-6.0 mL/kg/min (p<0.0001). Isolating the effects of reduction in body fat, we discern that these changes contributed to 0.3 of the 2.5 mL/kg/min increase in pkVO2 or 12% of the increase in pkVO2 observed. CONCLUSIONS: Changes in body composition, as a consequence of dietary and exercise modification, contribute to 12% of the "observed" improvement noted in weight-adjusted peak aerobic capacity following cardiac rehabilitation and exercise training. Changes in pkVO2 lean should be used by investigators to assess the singular effects of exercise conditioning alone.  相似文献   

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Forty-two men and women aged 70 to 79 years were studied to assess the effects of 6 months of endurance or resistance training and subsequent cessation of training on glucose tolerance, plasma insulin responses, serum triglyceride and cholesterol levels, and plasma dehydroepiandrosterone (DHEA) levels. The endurance training group (n = 16) exercised at 75% to 85% heart rate reserve for 35 to 45 minutes three times per week; the resistance training group (n = 17) completed one set of eight to 12 repetitions on 10 Nautilus machines three times per week. No significant changes in any variables occurred in a control group (n = 9). Maximal oxygen consumption (VO2max) increased by 20% with endurance training, but did not change with resistance training. Upper- and lower-body strength increased in the resistance training group, but did not change with endurance training. Neither group changed their body weight with training, but the endurance training group elicited a significant reduction in their sum of seven skinfolds and percent body fat. Neither group altered their glucose tolerance with training; however, the endurance training group had lower plasma insulin responses after training compared with the other two groups. Serum lipid and plasma DHEA levels did not change in either the endurance or resistance training groups. Ten days of no exercise following training did not significantly alter body weight or composition, glucose tolerance, plasma insulin responses, or plasma DHEA levels in either the endurance training (n = 10) or resistance training (n = 14) group.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
Left ventricular (LV) hypertrophy, especially combined with an abnormal ST-T, is considered 1 of many coronary risk factors. Seven hundred forty-nine Japanese men were selected according to their electrocardiographic findings, i.e., normal electrocardiogram, LV hypertrophy without an abnormal ST-T segment, LV hypertrophy with a flat T wave, and LV hypertrophy with a negative T wave. Coronary risk factors were compared among these 4 age-matched groups. Groups with LV hypertrophy with negative or flat T waves had larger body mass index (24.9 vs 22.9 kg/m2), higher mean systemic blood pressure (111 vs 95 mm Hg), larger LV mass (265 vs 157 g), higher blood glucose (110 vs 100 mg/dl), higher serum triglyceride (148 vs 122 mg/dl), higher total cholesterol (206 vs 198 mg/dl), and lower high-density lipoprotein cholesterol (47 vs 54 mg/dl) than the normal group or the group with LV hypertrophy without T-wave change. Among these risk factors, blood pressure and glucose remained higher even after the adjustment by body mass index or by body mass index and blood pressure. Electrocardiographic LV hypertrophy with a changed T wave signified higher risk of coronary artery disease in Japanese men.  相似文献   

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Our aim was to develop a computer simulator program that allows patients to practise insulin dose and dietary adjustment on a day of planned exercise, and shows the resulting blood glucose response in an average diabetic patient. The degree of blood glucose change predicted by the program was determined from changes predicted by five local specialists in seven hypothetical scenarios involving exercise +/- dietary or insulin dose adjustments. The program was then tested against 18 outside specialists' responses in 7 different scenarios. The program simulates the 24 h glycaemic response after 45 min mild or moderate exercise starting 2 h after meals, as well as changes to this response induced by alterations in dietary carbohydrate and/or insulin dose. Coefficients of variation of specialists' blood glucose predictions were greater for exercise (35% local, 31% outside specialists) than dietary change (7% local, 10% outside specialists; p = 0.002-0.04). The program's predicted change in blood glucose levels in the seven scenarios correlated well with the outside specialists' corresponding mean predictions (r = 0.97; p = 0.0001). We conclude that specialists are less consistent in predicting glycaemic change with exercise than with dietary alteration. Nevertheless it is possible to represent their predictions in a computerized simulator for diabetic patient education.  相似文献   

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Data on coffee consumption were collected for 1074 adults attending for health checks in the OXCHECK study, to assess associations with serum lipids and blood pressure. Of the sample, 70.5% drank coffee, largely instant. Coffee had no significant effects on total or high-density lipoprotein (HDL) cholesterol or blood pressure, and was negatively correlated with serum triglycerides. The type of coffee drunk in the UK does not adversely effect these cardiovascular risk factors.  相似文献   

20.
The photodegradation of seven carbamate pesticides (bendiocarb, isoprocarb, promecarb, ethiofencarb, furathiocarb, fenoxycarb and pirimicarb), in aqueous solution, has been examined by GC-MS. The most general result was formation of the corresponding phenols. Irradiation of isoprocarb and promecarb also resulted in photo-Fries rearrangement to ortho- and para-hydroxybenzamides. In the case of ethiofencarb photocleavage of the carbon-sulfur bond gave 2-methylphenyl methylcarbamate as main product. Likewise, N-S bond cleavage occurred upon irradiation of furathiocarb, to allow the formation of the carbamate insecticide carbofuran, butyl methylcarbamate and carbofuranphenol. Under similar conditions, fenoxycarb gave p-phenylphenol and 2-hydroxydibenzofuran, through primary homolysis of the aryloxy-methylene bond. Finally, pirimicarb gave rise to 2-formylamino-5,6-dimethylpyrimidin-4-yl dimethylcarbamate.  相似文献   

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