彩超与GGT联合检测对酒精依赖患者酒精肝的诊断价值

目的:研究分析彩超和谷氨酰转肽酶(GGT)联合检测对酒精依赖患者酒精性脂肪肝诊断的临床意义。方法:对2013年5月-2014年4月于我院住院并诊断为酒精依赖的患者39例(研究组)行肝脏彩超及GGT检测,另选取同期来源于本院职工、进修医护人员40例为对照组,对其结果进行分析。结果:研究组血清GGT为(189.95±226.52)U/L,显著高于对照组的(26.85±18.94)U/L,差异有统计学意义(t=4.54,P0.001);研究组中彩超诊断为脂肪肝者的GGT水平与非脂肪肝者有明显差异(P0.05),且高于对照组中的脂肪肝者,差异有统计学意义(P0.05)。结论:对于酒精依赖患者,血清GGT是敏感性较高的检测指标,GGT的检测有利于酒精性疾病的早期发现。彩超与GGT联合检测能提高临床对酒精性脂肪肝的检出率。     

Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure

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Nitrogen demand of different yeast strains during alcoholic fermentation. Importance of the stationary phase

The nitrogen demand of industrial yeast strains were compared. Substantial differences were found between strains. These did not change regardless of the initial medium composition and added nitrogen source. To separately study growth and stationary phases, we ran fermentations with different nitrogen feeding profiles: a) exponentially fed fermentations with a long growth phase, and b) constant rate fermentations with nitrogen addition during the stationary phase. Differences between stains mostly appeared during the second phase. Measuring nitrogen requirements under such conditions would thus be an interesting complementary test when selecting new strains especially for enological purposes since most fermentation kinetics are nitrogen limited.     

Progressive liver,kidney, and heart degeneration in children and adults affected by TULP3 mutations

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Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men

Background: Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: −33T > C IL4, −174 G > C IL6, −251 T > A IL8 and 1188 A > C IL12B. Methods: 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation–maximization algorithm and haplotype frequencies were compared. Results: We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Conclusions: Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.     

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

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Physiological role of mitochondrial Ca2+ transport

A model has been proposed in which mitochondrial Ca²⁺ ion transport serves to regulate mitochondrial matrix free Ca²⁺ ([Ca²⁺]_m), with the advantage to the animal that this allows the regulation of pyruvate dehydrogenase and the tricarboxylate cycle in response to energy demand. This article examines recent evidence for dehydrogenase activation and for increases in [Ca²⁺]_m in response to increased tissue energy demands, especially in cardiac myocytes and in heart. It critiques recent results on beat-to-beat variation in [Ca²⁺]_m in cardiac muscle and also briefly surveys the impact of mitochondrial Ca^2– transport on transient changes in cytosolic free Ca²⁺ in excitable tissues. Finally, it proposes that a failure to elevate [Ca²⁺]_m sufficiently in response to work load may underlie some cardiomyopathies of metabolic origin.     

Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of alcoholic liver disease: functional independence of ATPase activity and chaperone function

Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial but clearly involves oxidative stress and inflammation. Currently, conflicting reports exist regarding the role of endoplasmic reticulum (ER) stress in the etiology of ALD. The glucose-regulated protein 78 (GRP78) is the ER homolog of HSP70 and plays a critical role in the cellular response to ER stress by serving as a chaperone assisting protein folding and by regulating the signaling of the unfolded protein response (UPR). Comprising three functional domains, an ATPase, a peptide-binding, and a lid domain, GRP78 folds nascent polypeptides via the substrate-binding domain. Earlier work has indicated that the ATPase function of GRP78 is intrinsically linked and essential to its chaperone activity. Previous work in our laboratory has indicated that GRP78 and the UPR are not induced in a mouse model of ALD but that GRP78 is adducted by the lipid electrophiles 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of GRP78 has the potential to contribute to pathogenesis in ALD, we investigated the functional consequences of aldehyde adduction on GRP78 function. Identification of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked propensity for Lys and His adduction within the ATPase domain and a relative paucity of adduct formation within the peptide-binding domain. Consistent with these findings, we observed a concomitant dose-dependent decrease in ATP-binding and ATPase activity without any discernible impairment of chaperone function. Collectively, our data indicate that ATPase activity is not essential for GRP78-mediated chaperone activity and is consistent with the hypothesis that ER stress does not play a primary initiating role in the early stages of ALD.     

RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy

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An analytical comparison of cobalt cardiomyopathy and idiopathic dilated cardiomyopathy

Toxic cardiomyopathy (TC) has a rapid clinical course and morphologically resembles idiopathic dilated cardiomyopathy (IDC). To further characterize TC, we used light microscopy to compare lesions caused by cobalt (Co) to those of IDC. Cobalt levels were also measured as a chemical marker to differentiate TC from IDC. We reviewed cases with TC and IDC and excluded all cases with chemotherapy-induced myopathy and catecholamine toxicity as well as cases with possible infectious, ischemic, or hypersensitivity-induced myopathies. We compared the light microscopic findings of 12 TC cases to 12 cases of IDC, and measured trace Co levels on digested heart tissue samples. The TC cases had prominent myofibrillar loss and atrophy; no cases had neutrophil infiltration or frank myocyte necrosis. In contrast, IDC had minimal myofibril loss and atrophy. Cobalt levels in the range of 0.6 to 5.45 μg/g of dry tissue were obtained for the TC cases, while IDC demonstrated Co levels of 0.01–0.2 μg/g. Distinction between TC and IDC is predominantly a function of myocyte change, with TC showing myofibrillar loss and atrophy in the absence of inflammatory infiltrates and fibrosis; IDC is predominantly associated with myocyte hypertrophy, atrophy, and fibrosis. The opinions or assertions expressed herein are the private views of the authors and are not to be construed as official or as representing the views of the Armed Forces Institute of Pathology, the Department of the Army or the Department of Defense.