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.     

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.     

Lead concentrations in maternal and cord blood in women users of surma eye cosmetics

A prospective study was undertaken to analyse the lead concentrations in maternal and cord blood of 71 pregnant Arab women at term who used eye cosmetics, particularly "surma". A total of 64 mothers (90%) used eye cosmetics throughout pregnancy, and, of these, 45% used surma. The lead content of the cosmetics available in the market was found to vary between zero and 88%. The mean lead concentrations in all blood samples were higher than the accepted natural levels of 0.001 mumol/l, but lower than the subtoxic level of 1.9 mumol/l. The mean lead concentration of all samples was lower than the subtoxic level of 1.9 mumol/l but higher than that quoted in the literature and suggested to be a natural level (0.001 mumol/l). This indicates that other lead pollutants may be involved. Lead concentrations in maternal and cord blood correlated well, but did not show any significant difference between surma and non-surma users. None of the newborns showed apparent congenital anomalies and their birthweights were comparable to average Saudi birthweights.     

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     

Immunomodulatory effect of Hypoderma lineatum antigens: in vitro effect on bovine lymphocyte proliferation and cytokine production

This study examines the immunomodulatory effect of a crude larval extract (CLE), obtained from first stage larvae (L1) of H. lineatum , and the purified fractions hypodermin A (HyA), HyB and HyC. Proliferative responses of peripheral blood mononuclear cells (PBMC) from uninfested and previously infested cattle and the production of the cytokines IL-10, IL-4 and IFN-γ, in response to concanavalin A (Con A), were determined. The stimulation index of peripheral blood mononuclear cells from uninfested cattle was significantly lower than that from infested animals with the different antigens assayed. The HyA was the antigen that most inhibited the proliferative response, followed by the HyB, the HyC and the CLE. This hypodermin provoked an increase of IFN-γ and a suppression of IL-10 production that would support a Th1-like cytokine response. The HyB reduced the production of IL-10 stimulated by the Con A in cultures from infested animals. The HyC did not modulate the production of cytokines. Finally, the CLE induced a marked suppression in the production of the different cytokines in cultures from naïve and previously sensitized animals. Our results indicate that Hypoderma larval secretions are comprised of different components (hypodermins) that individually induce distinct but partially overlapping modulatory responses.     

Parity and vitamin D metabolites

Twenty-five hydroxycalciferol (25-OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium (Ca), phosphorus (P), alkaline phosphatase, and total protein were estimated in 86 Saudi pregnant women. They were divided into two groups, group I, parity 5 or more, and group II, parity 4 or less. The mean level of 25-OHD was 10.4 (S.D. 6.5) ng/ml in group I, and for group II 8.2 (6.1) ng/ml with no significant statistical difference between the groups. 1,25(OH)2D mean levels, in group I 45.5 (S.D. 30.2) ng/ml and in group II 36.9 (S.D. 27.1) pg/ml, also showed no significant difference. Levels of vitamin D metabolites were comparable with non-pregnant levels in Saudi Arabia but lower than others reported in Western populations. We found no effect of increasing parity on levels of vitamin D metabolites in our study.     

新疆铁路工人1001名体质状态相关分析

目的:调查新疆铁路工人的体质状况,并分析体质量指数和血糖、血脂及肝胆疾病之间的关系。方法:调查于2006-02/03进行。选择新疆乌鲁木齐铁路局公务段(盐湖-乌西)铁路职工1001人,测量其身高、体质量,计算体质量指数(<18.5kg/m2为体质量过低,18.5～24.9kg/m2为正常,25.0～29.9kg/m2为超重,>30kg/m2为肥胖);检测血脂(总胆固醇≥5.7mmol/L为高胆固醇血症;三酰甘油≥1.7mmol/L为高三酰甘油血症)、空腹血糖(≥7mmol/L为高血糖);B超观察肝、胆、脾、肾等器官。结果:受试者1001人全部进入结果分析。①体质量指数、三酰甘油、胆固醇、血糖值男女间未见差异。②体型正常者598人(59.74%),超重和肥胖者385人(38.46%)。③高三酰甘油症检出率:肥胖组明显高于体质量过低和正常组(58.33%,23.08%,7.32%,P<0.01);女性明显高于男性(23.95%,3.41%);体型正常者中女性明显高于男性(25.63%,0.68%)。④高胆固醇症、高血糖检出率男女比较差异不显著(P>0.05);超重者中女性高血糖检出率高于男性(10.14%,3.61%,P<0.05)。⑤脂肪肝检出率肥胖者最高为53.84%,体质量过低者最低5.56%;男性脂肪肝检出率高于女性(22.28%,16.81%,P<0.05);胆囊炎、胆结石检出率男女比较差异不显著。结论:①1001名铁路工人中体型异常者占40.36%,其中超重和肥胖者占38.66%。②随体质量指数增加,脂肪肝、高血脂检出率明显增加。