Comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients

BACKGROUND: Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures. METHODS: The consumption of substances was investigated using biological measures (urine cotinine, cannabis, opiates, cocaine, amphetamines and barbiturates; blood carbohydrate-deficient transferrin [CDT] and gamma-glutamyl transferase [GGT]) in 486 consecutively admitted psychiatric patients, one day following their hospitalization. Patients' self-reports of alcohol, tobacco and illicit drugs consumption were recorded. Socio-professional and familial data were also recorded. RESULTS: The results show a low correlation between biological measures and self-reported consumption of alcohol and illicit drugs. Fifty-two percent of the patients under-reported their consumption of illicit drugs (kappa=.47). Patients with schizophrenia and personality disorders were more likely to disclose their illicit drug consumption relative to patients suffering from mood disorders and alcohol dependence. Fifty-six percent of patients underreported alcohol use, as evaluated by CDT (kappa=.2), and 37% underreported when using the CDT+GGT measure as an indicator. Smoking appeared to be reported adequately. In the study we observed a strong negative correlation between cannabis use and age, a strong correlation between tobacco and cannabis use, and correlations between tobacco, cannabis and alcohol consumption. CONCLUSION: This study is the first to compare self-reports and biological measures of alcohol, tobacco and illicit drug uses in a large sample of inpatients suffering from various categories of psychiatric illnesses, allowing for cross-diagnosis comparisons.     

丁胱亚磺酰亚胺排空组织谷胱甘肽对大鼠心肌谷胱甘肽系统的影响

目的:观察采用谷氨酰半胱氨酸合成酶抑制剂--丁胱亚磺酰亚胺(BSO)排空大鼠心肌谷胱甘肽(GSH)是否影响大鼠心肌组织GSH的稳态,以及是否对GSH代谢相关酶活性及mRNA表达产生影响.方法:采用长时间力竭运动、注射BSO排空GSH两种实验模型,比较对照组与注射BSO组SD大鼠心肌在静息状态和长时间力竭运动后GSH状态及其代谢变化.结果:注射BSO 8天后,大鼠心脏GSH含量分别为对照组?%,且GSH的下降伴随着氧化型谷胱甘肽(GSSG)的下降,GSH/GSSG的比值无显著变化.GSH排空导致GSH代谢酶活性发生适应性变化,注射BSO后心肌中谷胱甘肽过氧化物酶(GPX)活性与对照组相比显著下降(P < 0.001).注射BSO组与对照组相比,心肌谷氨酰转肽酶(GGT)活性显著增加(P < 0.05).注射BSO力竭组与注射BSO组相比,心肌GGT活性显著增加(P < 0.001),心肌注射BSO抑制γ-谷氨酰半胱酸合成酶(GCS)活性,注射BSO力竭组大鼠心肌GCS mRNA表达量高于注射BSO组,表明极度排空谷胱甘肽后,GCS mRNA表达量的增加可能是机体产生的应激反应.     

Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is characterized by pruritus, intrahepatic cholestasis, low serum gamma-glutamyltransferase levels, and characteristic "Byler bile" on electron microscopy. Many patients require liver transplantation, but partial external biliary diversion (PEBD) has shown therapeutic promise. However, the effect of PEBD on liver morphology and bile composition has not been evaluated. METHODS: We reviewed liver biopsy specimens from 3 children with low gamma-glutamyltransferase PFIC before and after PEBD. Follow-up liver biopsies were performed 9-60 months after PEBD. Light and electron microscopic features were scored blindly. Biliary bile acid composition was analyzed by gas chromatography-mass spectrometry before and after PEBD in 1 patient and after PEBD in 2 patients. RESULTS: Following PEBD, all patients improved clinically. Preoperative biopsy specimens showed characteristic features of PFIC, including portal fibrosis, chronic inflammation, cholestasis, giant cell transformation, and central venous mural sclerosis. Ultrastructural findings included coarse, granular canalicular Byler bile, effaced canalicular microvilli, and proliferative pericanalicular microfilaments. Following diversion, histology showed almost complete resolution of cholestasis, portal fibrosis, and inflammation with resolution of ultrastructural abnormalities. Biliary bile acids before PEBD consisted predominantly of cholic acid. After PEBD, the proportion of chenodeoxycholic acid increased significantly in 1 patient and was above the PFIC range in a second patient. CONCLUSIONS: The resolution of hepatic morphologic abnormalities following PEBD supports PEBD as an effective therapy for PFIC. The improved biliary bile acid composition suggests enhanced bile acid secretion after PEBD, perhaps by induction of alternative canalicular transport proteins.     

γ-谷氨酰转移酶mRNA亚型对肝细胞癌变的监测

目的 探讨γ-谷氨酰转移酶（GGT）mRNA亚型的转化与原发性肝癌（HCC）发生的关系,寻找肝癌早期诊断的新方法。方法 以逆转录聚合酶链反应方法检测正常对照组、非癌肝病组、肝癌组及肝转移癌肝组织及外周血的3种GGTmRNA亚型(A、B、C亚型)。结果 正常肝纤维、非癌肝病的肝组织及肝转移癌癌周组织主要的GGTmRNA类型为A亚型,肝癌组织、癌旁组织及远癌组织GGTmRNA-B亚型的阳性率显著高于正常肝脏及非癌肝癌的肝组织（P＜0．05）,癌组织GGT mRNA-A亚型阳性率明显低于正常对照及非癌肝病组（P＜0．05）。在26例HCC中有12例外周血中检出GGTmRNA-B亚型,甲胎蛋白阴性的10例HCC中有5例检出GGTmRNA-B亚型。结论 GGT mRNA亚型转化与肝癌发生有密切关系,分析GGT基因可望成为监测肝细胞癌变的灵敏方法。     

Liver steatosis assessment: Correlations among pathology,radiology, clinical data and automated image analysis software

Quantitating hepatic steatosis is important in many liver diseases and liver transplantation. Since steatosis estimation by pathologists has inherent intra- and inter-observer variability, we compared and contrasted computerized techniques with magnetic resonance imaging measurements, pathologist visual scoring, and clinical parameters. Computerized methods applied to whole slide images included a commercial positive pixel count algorithm and a custom algorithm programmed at our institution. For all liver samples (n = 59), including pediatric, adult, frozen section, and permanent specimens, statistically significant correlations were observed between pathology, radiology, and each image analysis modality (r = 0.75–0.97, p < 0.0001), with the strongest correlations in the pediatric cohort. Statistically significant relationships were observed between each method and with body mass index (r = 0.37–0.56, p from <0.0001 to <0.05) and with albumin (r = 0.55–0.64, p < 0.05) but not with alanine aminotransferase or aspartate aminotransferase. Although pathologist assessments correlated (r = 0.64–0.86, 0.92–0.97, and 0.78–0.91 for microvesicular, macrovesicular, and overall steatosis, respectively), the absolute values of hepatic steatosis visual assessment were susceptible to intra- and inter-observer variability, particularly for microvesicular steatosis. Image analysis, pathologist assessments, radiology measurements, and several clinical parameters all showed correlations in this study, providing evidence for the utility of each method in different clinical and research settings.     

Oridonin induces ferroptosis by inhibiting gamma‐glutamyl cycle in TE1 cells

Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC–MS/MS metabolomics profiling on TE1 cells, which show that gamma‐glutamyl amino acids (gamma‐glutamylleucine, gamma‐glutamylvaline), 5‐oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma‐glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma‐glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin‐cysteine (Ori‐Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma‐glutamyl cycle, thereby inducing ferroptosis to exert anti‐cancer activity.