PGE1 abolishes the mitochondrial-independent cell death pathway induced by D-galactosamine in primary culture of rat hepatocytes

Background and Aim:  PGE₁ reduces in vivo and in vitro D-galactosamine (D-GalN)-induced cell death in hepatocytes. The present study was undertaken to elucidate the intracellular pathway by which D-GalN induces cell death in cultured hepatocytes. In addition, we evaluated if PGE₁ was able to modulate different parameters related to D-GalN-induced apoptosis in cultured rat hepatocytes.
Methods:  Hepatocytes were isolated from male Wistar rats (225–275 g) by the classical collagenase procedure. PGE₁ (1 µM) was administered 2 h before D-GalN (5 mM) in primary culture of rat hepatocytes. Apoptosis was determined by DNA fragmentation and caspase-3, -6, -8 and -9 activation in hepatocytes. Caspase activation was evaluated by the detection of the related cleaved product and its associated activity. Cell necrosis was determined by the measurement of lactate dehydrogenase (LDH) activity in culture medium. To elucidate the role of mitochondria, we measured neutral (nSMase) and acid (aSMase) sphingomyelinase, as well as the expression of cytochrome c in mitochondria and cytoplasm fractions from D-GalN treated hepatocytes.
Results:  D-GalN induced caspase-3 activation and DNA fragmentation in hepatocytes. This apoptotic response was not associated with the activation of caspase-6, -8 or -9. The use of specific inhibitors confirmed that only caspase-3 was involved in D-GalN-induced apoptosis. D-GalN did not modify nSMase and aSMase activities, nor mitochondrial cytochrome c release in hepatocytes.
Conclusions:  D-GalN induced apoptosis through caspase-3 activation but without modification of the activity of caspase-6, -8, -9, SMases or cytochrome c release. PGE₁ appears to prevent D-GalN-induced apoptosis by a mitochondria-independent mechanism.     

Effect of exercise during the follicular and luteal phases on indices of oxidative stress in healthy women

PURPOSE: Eleven healthy nonsmoking women (24+/-1.1 yr) exercised for 30 min at 75-80% VO2max during the follicular (F) and luteal (L) phases of their menstrual cycle to determine whether menstrual phase influenced indices of oxidative stress. METHODS: Subjects completed the exercise in a randomized order. Subjects reported between 0800 and 0900 in a postabsorptive state, rested for 15-30 min, and had a venous blood sample obtained by Vacutainer before and after exercise. RESULTS: Resting estradiol was 54.4+/-12.0 pg.mL(-1) for F phase and was significantly higher in L phase (147.2+/-25.5 pg.mL(-1)). Plasma malondialdehyde and thiobarbituric acid substances were no different before and after exercise independent of menstrual cycle phase. No differences in resting blood total glutathione (TGSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) were evident comparing the F and L phases. After exercise, TGSH decreased (P = 0.03) but reached significance only in the F phase = 8.1 %(P = 0.04), L phase = 2.5% (P = 0. 15). Exercise increased GSSG 10.5% in F (P = 0.15) and 27.8% in L phases(P = 0.01). GSH decreased after exercise independent of menstrual phase (F = 17%, L = 16%, P = 0.01). CONCLUSION: These data suggest that 30 min of moderate-intensity exercise in female subjects can result in mild oxidative stress as indicated by blood glutathione status and that menstrual cycle phase has minimal influences on these exercise responses.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

A dermoid cyst fistulating with the transverse colon

We present a rare case of fistulation of a dermoid cyst with the transverse colon. We illustrate how an infected dermoid cyst can be diagnosed as an appendix abscess although the management of these is quite different. The general surgeon should be aware of this as a differential diagnosis for an appendix abscess.     

Acute effects of second-hand smoke on complete blood count

We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on complete blood count (CBC) markers in a controlled simulated bar/restaurant environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were collected at the baseline at 30?min during each exposure, and at 0, 0.5, 1, 2, 3, and 4?h after each exposure. The values of white blood cells (WBC) at 1?h (p?=?0.010), 3?h (p?=?0.040), and 4?h (p?=?0.008) following SHS were significantly increased compared with the baseline values. Also, there was a positive association between the WBC and cotinine levels (r?=?0.28, p?=?0.007). A 1-h exposure to SHS at bar/restaurant levels significantly increased the WBC for at least 4?h following the exposure time. This effect of SHS on WBC has dose–response characteristics and should be considered to prescribing CBC.     

Exposure to secondhand smoke promotes sympathetic activity and cardiac muscle cachexia

Recent trials demonstrated that a single brief exposure to secondhand smoke (SHS) generates acute adverse health effects. We evaluated the acute (immediately after exposure) and short-term (0.5, 1, 2, 3 and 4?h after exposure) effects of SHS on cardiac autonomic control and myocardial integrity. Nineteen adult healthy never-smokers underwent a 1?h exposure to SHS at bar/restaurant levels and a 1?h control exposure. Heart rate variability (HRV), serum cotinine, and six cardiac protein markers were assessed before, during, and up to four hours following each exposure. SHS reduced the standard deviation of normal-to-normal intervals and increased cotinine levels, creatine kinase (CK)-MB, and myoglobin (p?相似文献   

1型糖尿病患儿的课堂注意力：稳定血糖的效果

目的:观察评估通过使用胰岛素泵以稳定血糖,是否可以改善1型糖尿病患儿的课堂注意力。试验设计:对4例患有1型糖尿病且血糖水平不稳定的患儿在课堂中的表现进行为期10d的观察。在放置胰岛素泵,控制血糖后再观察10d。利用改良多基线设计血糖控制水平是否与患儿专注于功课和走神行     

Effects of interaction between angiotensin I-converting enzyme polymorphisms and lifestyle on adiposity in adolescent Greeks

Genetic variation in the human angiotensin I-converting enzyme (ACE) gene has been associated with many heritable traits, including obesity. Herein, we report the results of a study of obesity-related phenotypes and lifestyle in 1016 teen-aged Greeks. We show that there is a strong association (p = 0.001) between subcutaneous fat and the ACE insertion/deletion (I/D) polymorphism in females, possession of genotypes containing the D allele being associated with increased fat thickness. This association is strongest in females who participate in no extra exercise and accounts for 6.5% of the phenotypic variance in fat thickness by ANOVA. The association is additive, with the mean phenotypic values in heterozygotes intermediate between the means of the two homozygotes, and the association acts at both extremes of the fat thickness distribution in a classical polygenic manner. Other ACE polymorphisms (rs4424958, rs4311) that define major haplotypes in European populations fail to provide stronger associations with the subcutaneous fat phenotype. Because ACE I/D is the polymorphism most strongly associated with circulating ACE levels in European populations, we propose that the functional allelic differences that influence circulating ACE levels also mediate the associations with the obesity-related phenotypes studied here.     

The effects of muscle damage on running economy in healthy males

Published information on aspects related to muscle damage and running economy is both limited and contradictory. To contribute to the current debate, we investigated the effects of an eccentric exercise session on selected muscle damage indices in relation to running economy using 10 (mean age 23 +/- 1 years) healthy male volunteers. The eccentric exercise session consisted of 120 (12 x 10) maximal voluntary repetitions by each randomly selected leg at the angular velocity of 1.05 rad . s (-1). Muscle damage (creatine kinase, delayed onset muscle soreness, range of movement, and eccentric, concentric and isometric [at 60 degrees and 110 degrees knee flexion] peak torque) and running economy (oxygen consumption, pulmonary ventilation, respiratory exchange ratio and breaths per minute during treadmill running at 133 and 200 m . min (-1)) indicators, were assessed pre-, 24-, 48-, 72- as well as 96-h after exercise. All muscle damage indicators revealed significant changes at almost all time-points of assessment compared to pre-exercise data (p < 0.05). However, none of the running economy parameters disclosed any significant change throughout the study (p > 0.05). It was concluded that changes in muscle damage and muscle performance as measured in this study are not reflected by concomitant alterations in running economy at submaximal intensities.