Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.     

Reassessment of the utility of fetal umbilical vein diameter in the management of isoimmunization

High-resolution ultrasound has been recently introduced in the management of many conditions in which the fetus is at risk. In the detection of severe erythroblastosis fetalis, sonographic evaluation of fetal anatomic changes is being used in association with amniotic fluid spectral analysis to assess the degree of the hemolytic process. In 1981 it was reported that sonographically detected umbilical vein dilatation, resulting from hepatic congestion, could be used as a sign of impending fetal compromise. We analyzed data obtained from 47 patients in a total of 76 examinations, including sonographic measurement of umbilical vein diameter, associated ultrasound findings, results of amniotic fluid spectral analyses, and neonatal outcome. The collected data, divided in two groups according to the results of amniotic fluid spectral analyses (less than high zone II and greater than or equal to high zone II), showed that the sonographic measurement of umbilical vein diameter does not differ significantly between the two groups (p greater than 0.05). Therefore, the present and relatively large series demonstrates that dimensions of the umbilical vein cannot be used as a reliable predictor of worsening fetal disease.     

Independent and incremental prognostic value of exercise thallium single-photon emission computed tomographic imaging in women

Background  

This study examined the independent and incremental prognostic value of exercise thallium single-photon emission computed tomographic imaging in 212 women who also underwent coronary angiography.     

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices

BackgroundThe treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse.Patients and MethodsA retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health’s Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice.ResultsA total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment.ConclusionIn the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.     

Relaxin levels in ovum donation pregnancies

STUDY OBJECTIVE: To investigate the relative contributions of the corpus luteum (CL) and the placenta to the circulating levels of relaxin during pregnancy. PATIENTS: Forty-one patients in whom pregnancy had been achieved by ovum donation. RESULTS: Relaxin was not detected in the serum of 36 patients; in the remaining 5, although it was detectable, the levels were markedly reduced when compared with those in normal pregnancies. CONCLUSION: These results demonstrate that the CL is essential for the maintenance of normal circulating levels of relaxin during pregnancy.     

The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program

The effect of the dose of human chorionic gonadotropin (hCG) on oocyte retrieval in an in vitro fertilization (IVF) program was studied. Following ovulation induction using clomiphene citrate and either pure follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG), hCG was administered at a dose of 2000 IU (n = 88), 5000 IU (n = 110), and 10,000 IU (n = 104). There was a significantly lower successful oocyte recovery in patients who received 2000 IU of hCG (77.3%) compared with patients who received either 5000 IU of hCG (95.5%) or 10,000 IU of hCG (98.1%; P less than 0.001). There was no significant difference between 5000 or 10,000 IU of hCG. In patients who received 2000 IU of hCG, successful oocyte recovery was significantly lower when pure FSH was used (60%) compared with those who received hMG (84.1%; P less than 0.03). Patients have different thresholds for follicular response to hCG and the recommended minimum dose of hCG should be at least 5000 IU.     

Transesophageal echocardiographic identification of right vertebral artery

We describe a transesophageal technique for identifying the origin and precervical course of the right vertebral artery with the probe positioned in the upper esophagus. The technique was successful in 9 of 11 patients in whom it was attempted.