Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been proposed as a new target for type 2 diabetes drugs. The aim of the present study was to assess the effects of inhibition of 11 beta-HSD1 on blood glucose levels, glucose tolerance, and insulin sensitivity in mouse models of type 2 diabetes. BVT.2733 is an isoform-selective inhibitor of mouse 11 beta-HSD1. Hyperglycemic and hyperinsulinemic ob/ob, db/db, KKAy, and normal C57BL/6J mice were orally administered BVT.2733 (200 mg/kg.d, twice daily). In hyperglycemic, but not in normal mice, BVT.2733 lowered circulating glucose (to 50-88% of control) and insulin (52-65%) levels. In oral glucose tolerance tests in ob/ob and KKAy mice, glucose concentrations were 65-75% of vehicle values after BVT.2733 treatment, and in KKAy mice insulin concentrations were decreased (62-74%). Euglycemic, hyperinsulinemic clamps demonstrated decreased endogenous glucose production (21-61%). Analysis of hepatic mRNA in KKAy mice showed reduced phosphoenolpyruvate carboxykinase mRNA (71%). A slight reduction in food intake was observed in ob/ob and KKAy mice. Cholesterol, triglycerides, and free fatty acid levels were decreased to 81-86% in KKAy mice after a 4-h fast. The results support previous suggestions that selective 11 beta-HSD1 inhibitors lower blood glucose levels and improve insulin sensitivity in different mouse models of type 2 diabetes.     

Impact of age on intermittent hypoxia in obstructive sleep apnea: a propensity-matched analysis

Purpose

To determine independent relationship of aging with chronic intermittent hypoxia, we compared hypoxia-related polysomnographic variables of geriatric patients (aged ≥ 65 years) with an apnea–hypopnea index (AHI)-, gender-, body mass index (BMI)-, and neck circumference-matched cohort of non-geriatric patients.

Methods

The study was conducted using clinical and polysomnographic data of 1280 consecutive patients who underwent complete polysomnographic evaluation for suspected sleep-disordered breathing (SDB) at a single sleep disorder center. A propensity score-matched analysis was performed to obtain matched cohorts of geriatric and non-geriatric patients, which resulted in successful matching of 168 patients from each group.

Results

Study groups were comparable for gender (P = 0.999), BMI (P = 0.940), neck circumference (P = 0.969), AHI (P = 0.935), and severity of SDB (P = 0.089). The oximetric variables representing the duration of chronic intermittent hypoxia such as mean (P = 0.001), the longest (P = 0.001) and total apnea durations (P = 0.003), mean (P = 0.001) and the longest hypopnea durations (P = 0.001), and total sleep time with oxygen saturation below 90% (P = 0.008) were significantly higher in the geriatric patients as compared with younger adults. Geriatric patients had significantly lower minimum (P = 0.013) and mean oxygen saturation (P = 0.001) than non-geriatric patients.

Conclusions

The study provides evidence that elderly patients exhibit more severe and deeper nocturnal intermittent hypoxia than the younger adults, independent of severity of obstructive sleep apnea, BMI, gender, and neck circumference. Hypoxia-related polysomnographic variables in geriatric patients may in fact reflect a physiological aging process rather than the severity of a SDB.

     

Subxiphoid versus Intercostal Chest Tubes: Comparison of Postoperative Pain and Pulmonary Morbidities after Coronary Artery Bypass Grafting

Chest tubes are one cause of pain after cardiac surgery. In a prospective, randomized study, we investigated the effects of the position of chest tubes on acute postoperative pain and pulmonary morbidities in patients who underwent coronary artery bypass grafting.From June through December 2010, 40 patients who underwent elective coronary artery bypass grafting were enrolled in the study. We investigated 2 randomized groups of patients: Group 1 (n-20) had a left chest tube inserted through the midline inferior to the xiphoid process (subxiphoid approach), and Group 2 (n-20) had a left chest tube inserted through the 6th intercostal space along the anterior axillary line (intercostal approach). We compared the results with respect to postoperative pain, the need for analgesic agents, chesttube drainage, pulmonary morbidities, and duration of hospitalization.The intensity of postoperative pain was similar between the groups. The cumulative doses of analgesic agents, incidence of pulmonary morbidities, and duration of hospitalization were also similar. Pleural effusion and atelectasis were each diagnosed in 3 patients in Group 1 (15%) and 1 patient in Group 2 (5%) (both P=0.68). Two of the patients in Group 1 required drainage of the pleural effusion.In our study, we found that the subxiphoid and intercostal approaches for chest-tube placement yielded similar clinical outcomes.     

A novel model for testing the efficiency of removal of calcium hydroxide from complex root canal anatomies

The purpose of this study was to evaluate the efficacy of several irrigation protocols in the removal of calcium hydroxide [Ca(OH)₂] from simulated internal root resorption cavities in a complex root canal anatomy model. The 20° to 35° curved mesiobuccal roots of 94 maxillary molars were sectioned longitudinally; internal resorption cavities were prepared in the apical third of the canal walls. Calcium hydroxide was placed into the cavities and the root halves reassembled. Four teeth were used as controls, and 90 teeth were randomly divided into six experimental groups (n = 15), according to the irrigation protocols used: syringe irrigation; H₂O₂ (HP); Navitip FX; Vibringe‐syringe; Vibringe‐NaviTip FX; ultrasonically activated irrigation (UAI) using an ultrasonic K‐file. In the HP group, 2.5% NaOCl and 3% H₂O₂ were used, while 2.5% NaOCl and 17% EDTA were used in the remaining groups. Stereomicroscope images and radiographs were used to measure the remaining Ca(OH)₂. The model proved to be suitable for simulating complex anatomy. Positive correlation was found between stereomicroscope and radiographic analyses (P < 0.05). UAI removed significantly more Ca(OH)₂ than the other experimental groups (P < 0.05). The HP group was the least efficient protocol (P < 0.05). It would appear that a reliable model has been developed that simulates complex root canal anatomy. Irrigant activation protocols enhanced Ca(OH)₂ removal.