N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents

Potent aryl hydrocarbon receptor agonists like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) cause oxidative stress and liver pathology, including fatty liver. Our question was whether dietary supplementation with N-acetylcysteine (NAC), an antioxidant, can prevent these adverse changes. Male Sprague-Dawley rats were fed a standard AIN-93G diet (sufficient in cysteine) or a modified diet supplemented with 1.0% NAC. After one week, rats on each diet were exposed to 0, 1, or 5μmol/kg body weight PCB 126 by i.p. injection (6 rats per group) and euthanized two weeks later. PCB-treatment caused a dose-dependent reduction in growth, feed consumption, relative thymus weight, total glutathione and glutathione disulfide (GSSG), while relative liver weight, glutathione transferase activity and hepatic lipid content were dose-dependently increased with PCB dose. Histologic examination of liver tissue showed PCB 126-induced hepatocellular steatosis with dose dependent increase in lipid deposition and distribution. Dietary NAC resulted in a reduction in hepatocellular lipid in both PCB groups. This effect was confirmed by gravimetric analysis of extracted lipids. Expression of CD36, a scavenger receptor involved in regulating hepatic fatty acid uptake, was reduced with high dose PCB treatment but unaltered in PCB-treated rats on NAC-supplemented diet. These results demonstrate that NAC has a protective effect against hepatic lipid accumulation in rats exposed to PCB 126. The mechanism of this protective effect appears to be independent of NAC as a source of cysteine/precursor of glutathione.     

Cholecystectomy,gallstones, tonsillectomy,and pancreatic cancer risk: a population-based case-control study in minnesota

Background:

Associations between medical conditions and pancreatic cancer risk are controversial and are thus evaluated in a study conducted during 1994–1998 in Minnesota.

Methods:

Cases (n=215) were ascertained from hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were randomly selected from the general population and frequency matched to cases by age and sex. The history of medical conditions was gathered with a questionnaire during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.

Results:

After adjustment for confounders, subjects who had cholecystectomy or gallstones experienced a significantly higher risk of pancreatic cancer than those who did not (OR (95% CI): 2.11 (1.32–3.35) for cholecystectomy and 1.97 (1.23–3.12) for gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48–0.94)). Increased risk associated with cholecystectomy was the greatest when it occurred ⩽2 years before the cancer diagnosis (5.93 (2.36–15.7)) but remained statistically significant when that interval was ⩾20 years (2.27 (1.16–4.32)).

Conclusions:

Cholecystectomy, gallstones, and tonsillectomy were associated with an altered risk of pancreatic cancer. Our study suggests that cholecystectomy increased risk but reverse causality may partially account for high risk associated with recent cholecystectomy.     

Evaluation of topical 0.03% flurbiprofen drops in the treatment of herpetic stromal keratitis

Purpose: The management protocol for herpetic stromal keratitis (HSK) is still controversial. We have attempted to compare the relative efficacy of topical dexamethasone 0.01 % and flurbiprofen 0.03% in combination with topical acyclovir 3% in HSK.
Methods: In this institutional, prospective, randomized, controlled, double-blind study, 45 clinically diagnosed cases of HSK were randomly distributed into three coded treatment groups — topical placebo, dexamethasone 0.01 %, and flurbiprofen 0.03% each in tapering frequency and in combination with acyclovir 3% ointment five times per day for four weeks. Therapeutic response was assessed every third day for four weeks. Decoding of the treatment groups was done at the conclusion of the study and data analysed.
Results: Four-week success rate was 93.3% (14 of 15) in the dexamethasone-acyclovir treatment group, 66.7% (10 of 15) in the flurbiprofen-acyclovir treatment group and 20% (3 of 15) in the placeboacyclovir treatment group.
Conclusion: While dexamethasone in combination with acyclovir gives the best results in HSK with minimal side-effects, the role of topical flurbiprofen seems promising.     

The effect of anti‐emetic doses of dexamethasone on postoperative blood glucose levels in non‐diabetic and diabetic patients: a prospective randomised controlled study

There are few data regarding postoperative hyperglycaemia in non‐diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty‐five non‐diabetic patients and patients with type‐2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non‐diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l^?1 vs. 7.8 (1.4) mmol.l^?1, p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l^?1 vs. 10.7 (2.4) mmol.l^?1, p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non‐diabetics and diabetics.     

Evaluation of Placentation and the Role of the Aryl Hydrocarbon Receptor Pathway in a Rat Model of Dioxin Exposure

Background: Our environment is replete with chemicals that can affect embryonic and extraembryonic development. Dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are compounds affecting development through the aryl hydrocarbon receptor (AHR).Objectives: The purpose of this investigation was to examine the effects of TCDD exposure on pregnancy and placentation and to evaluate roles for AHR and cytochrome P450 1A1 (CYP1A1) in TCDD action.Methods: Actions of TCDD were examined in wild-type and genome-edited rat models. Placenta phenotyping was assessed using morphological, biochemical, and molecular analyses.Results: TCDD exposures were shown to result in placental adaptations and at higher doses, pregnancy termination. Deep intrauterine endovascular trophoblast cell invasion was a prominent placentation site adaptation to TCDD. TCDD-mediated placental adaptations were dependent upon maternal AHR signaling but not upon placental or fetal AHR signaling nor the presence of a prominent AHR target, CYP1A1. At the placentation site, TCDD activated AHR signaling within endothelial cells but not trophoblast cells. Immune and trophoblast cell behaviors at the uterine–placental interface were guided by the actions of TCDD on endothelial cells.Discussion: We identified an AHR regulatory pathway in rats activated by dioxin affecting uterine and trophoblast cell dynamics and the formation of the hemochorial placenta. https://doi.org/10.1289/EHP9256