Role of insulin receptor substrate‐1 for diethylnitrosamine plus high‐fat diet‐induced hepatic tumorigenesis in mice

We investigated the role of insulin receptor substrate (Irs)‐1 for diethylnitrosamine (DEN) plus high‐fat (HF) diet‐induced hepatic tumorigenesis in mice. We gave DEN by intraperitoneal injection at the dose of 80 mg/kg to 18‐week‐old wild‐type (WT) and Irs1‐knockout (Irs1^−/−) mice, which were fed a HF diet from 8 weeks‐of‐age until they were killed (52 weeks). The Irs1^−/− mice showed significantly lower plasma alanine aminotransferase levels, triglyceride contents in the liver and also lower expression levels of the genes encoding inflammatory cytokines than the WT mice. The incidence of DEN plus HF diet‐induced hepatic tumors was 71.4% in the WT mice, whereas it was just 14.3% in the Irs1^−/− mice. The present study showed that Irs1 played an important role in DEN plus HF diet‐induced hepatic tumorigenesis.     

Usefulness of pet ownership as a modulator of cardiac autonomic imbalance in patients with diabetes mellitus, hypertension, and/or hyperlipidemia

Among patients with coronary artery disease, pet owners exhibit a greater 1-year survival rate than nonowners. Lifestyle-related diseases are well-known risk factors for coronary artery disease and induce imbalances in autonomic nervous activity. The purpose of the present study was to determine whether pet ownership modulates cardiac autonomic nervous activity imbalance in patients with lifestyle-related diseases such as diabetes mellitus, hypertension, and hyperlipidemia. A total of 191 patients (mean age 69 ± 8 years) were interviewed about their pet ownership status and were classified into pet owner and nonowner groups. After recording a 24-hour Holter electrocardiogram for heart rate variability analysis, frequency-domain and nonlinear-domain analyses were performed to determine the high-frequency (HF) and low-frequency (LF) components, LF/HF ratio, and entropy. The heart rate variability parameters were assessed for 24 hours, during the day (8.00 A.M. to 5.00 P.M.), and during the night (0:00 A.M. to 6.00 A.M.), and compared between the 2 groups. To evaluate the potential predictive factors for cardiac autonomic imbalance, univariate and multivariate analyses of HF and LF/HF were conducted for potential confounding variables. The pet owner group exhibited significantly greater HF(24h), HF(day), HF(night), entropy(24h), entropy(day), and entropy(night) and significantly lower LF/HF(24h) and LF/HF(night) compared to the nonowner group. On multivariate analysis, pet ownership was independently and positively associated with HF(24h,) HF(day), and HF(night) and inversely associated with LF/HF(24h) and LF/HF(night). In conclusion, these results suggest that pet ownership is an independent modulator of cardiac autonomic imbalance in patients with lifestyle-related diseases.     

Obstructive sleep apnea as a potential risk factor for aortic disease

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n?=?95) consisting of patients with thoracic aortic aneurysm (TAA, n?=?32), patients with abdominal aortic aneurysm (AAA, n?=?36), and patients with AD (n?=?27); and a control group (n?=?32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P?=?0.045, P?=?0.003, and P?=?0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ??15 events/h] was significantly higher in the first three groups (P?=?0.026, P?=?0.001, P?=?0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.