Opioids in the perifornical lateral hypothalamus suppress ethanol drinking

The opioid system is known to enhance motivated behaviors, including ethanol drinking and food ingestion, by acting in various reward-related brain regions, such as the nucleus accumbens, ventral tegmental area and medial hypothalamus. There is indirect evidence, however, suggesting that opioid peptides may act differently in the perifornical lateral hypothalamus (PF/LH), causing a suppression of consummatory behavior. Using brain-cannulated Sprague–Dawley rats trained to voluntarily drink 7% ethanol, the present study tested the hypothesis that opioids in the PF/LH can reduce the consumption of ethanol, with animals receiving PF/LH injections of the δ-opioid receptor agonist D-Ala2-met-enkephalinamide (DALA), the μ-receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), the κ-receptor agonist (±)-trans-U-50,488 methanesulfonate (U-50,488H), or the general opioid antagonist methylated naloxone (m-naloxone). The consumption of ethanol, lab chow, and water was monitored for 4 h after injection. The results showed that the three opioid receptor agonists injected into the PF/LH specifically and significantly reduced ethanol intake, while causing little change in chow or water intake, and the opposite effect, enhanced ethanol intake, was observed with the opioid antagonist. Of the three opioid agonists, the δ-agonist appears to produce the most consistent and long-lasting suppression of consumption. This effect was not observed with injections 2 mm dorsal to this area, focusing attention on the PF/LH as the main site of action. These results suggest that the opioid peptides have a specific role in the PF/LH of reducing ethanol drinking, which is distinct from their more commonly observed appetitive actions in other brain areas. The additional finding, that m-naloxone in the PF/LH stimulates ethanol intake in contrast to its generally suppressive effect in other regions, focuses attention on this hypothalamic area and its distinctive role in contributing to the variable effects sometimes observed with opioid antagonist therapy for alcoholism.     

Effect of lower limb compression devices on thermodilution cardiac output measurement

OBJECTIVE: The aim of this study was to determine whether lower limb (calf) sequential compression devices (SCDs) have a significant effect on thermodilution cardiac output measurements using a pulmonary artery catheter. DESIGN: Prospective clinical investigation. SETTING: Surgical and neurosurgical intensive care units in a university hospital. PATIENTS: A total of 43 patients with pulmonary artery catheters and bilateral lower limb SCDs. MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured (average of three) when the SCDs were off (T1), during the first 2-4 secs of the inflation cycle (T2), during seconds 4-8 of the inflation cycle (T3), and when the SCDs were off again (T4). Cardiac output measurements were consistently lower when measured during the SCD inflation cycle. The decrease in cardiac output ranged from 7.58% to 49.5%, with a mean reduction of 24.51% in the first 2-4 seconds and 20.61% during seconds 4-8 (p < .001). Two patients displayed an increase in cardiac output during the inflation cycle; one patient had an increase of 2.78% and the other an increase of 13.5%. In 11 patients, measurements were also made using a pulse contour-analysis cardiac output device, but no changes in pulse contour-analysis cardiac output were observed during the same time period. CONCLUSIONS: Thermodilution cardiac output measurements via a pulmonary artery catheter should not be done during the inflation cycle of lower limb SCDs because they produce a falsely low cardiac output.     

早期限饲对肉鸡脂质过氧化和抗氧化酶活性长期影响

目的：观察早期限饲（出雏后两周隔天饲喂）对肉鸡脂质过氧化作用和抗氧化酶活性产生的长期影响，并通过与后期限饲（屠宰前两周隔天饲喂）比较，观察不同阶段限饲对肉鸡血清、肝脏、胸肌、腓肠肌丙二醛浓度、超氧化物歧化酶和谷胱甘肽过氧化物酶活性的影响。方法：实验主要于2005—04／12在南京农业大学农业部动物生理生化重点开放实验室完成。实验分组：选取1日龄健康快三黄商品肉鸡100羽随机分为2组，对照组60羽，早期限饲组40羽。饲养至50日龄，从对照组随机选取20羽作为后期限饲组。实验处理：①早期限饲组，1-14日龄进行隔日限饲，以后自由采食。②后期限饲组，1～49日龄自由采食，50～63日龄进行隔日限饲。③对照组，全程自由采食。实验评估：记录每周体质量，检测14日龄对照组、早期限饲组，63日龄对照组、早期限饲组和后期限饲组血清、肝脏、胸肌、腓肠肌丙二醛浓度、超氧化物歧化酶和谷胱甘肽过氧化物酶活性。结果：100羽实验动物均进入结果分析。①14日龄早期限饲组肉鸡血清、肝脏、胸肌和腓肠肌丙二醛浓度、超氧化物歧化酶和谷胱甘肽过氧化物酶活性与对照组相比差异无显著性。②63日龄时早期限饲组血清丙二醛浓度和谷胱甘肽过氧化物酶活性均显著高于对照组（P〈0．05），肝脏超氧化物歧化酶活性显著低于对照组（P〈0．05）；后期限饲组血清丙二醛浓度以及超氧化物歧化酶和谷胱甘肽过氧化物酶活性均显著高于对照组（P〈0．05），而肝脏丙二醛浓度、胸肌超氧化物歧化酶活性显著低于对照组（P〈0．05），腓肠肌各项指标与对照组相比差异无显著性。后期限饲组血清谷胱甘肽过氧化物酶活性显著高于早期限饲组（P〈0．05）。后期限饲组肝脏丙二醛浓度显著低于早期限饲组，超氧化物歧化酶活性显著高于早期限饲组（P〈0．05）。结论：早期及后期限饲均能增强63日龄肉鸡体内整体水平脂质过氧化作用和抗氧化酶活性，早期限饲对肉鸡脂质过氧化作用和血清抗氧化酶活性的即时影响表现不明显，但其影响可以持续到后期。     

Towards a subsiding diabetes epidemic: trends from a large population-based study in Israel

Background

With increasing diabetes prevalence worldwide, an impending diabetes “pandemic” has been reported. However, definitions of incident cases and the population at risk remain varied and ambiguous. This study analyzed trends in mortality and screening that contribute to diabetes prevalence and incidence, distinguishing between new incident cases and newly detected cases.

Methods

In an integrated provider-and-payer-system covering 53% of Israel’s population, a composite diabetes case-finding algorithm was built using diagnoses, lab tests, and antidiabetic medication purchases from the organization’s electronic medical record database. Data were extracted on adult members aged 26+ each year from January 1, 2004 through December 31, 2012. Rates of diabetes prevalence, incidence, screening, and mortality were reported, with incidence rates evaluated among the total, “previously-screened,” and “previously-unscreened” at-risk populations.

Results

There were 343,554 diabetes cases in 2012 (14.4%) out of 2,379,712 members aged 26+. A consistent but decelerating upward trend in diabetes prevalence was observed from 2004-2012. Annual mortality rates among diabetics decreased from 13.8/1000 to 10.7/1000 (p = 0.0002). Total population incidence rates declined from 13.3/1000 in 2006 to 10.8/1000 in 2012 (p < 0.0001), with similar incidence trends (13.2/1000 to 10.2/1000; p = 0.0007) among previously-screened at-risk members, and a rise in testing rates from 53.0% to 66.7% (p = 0.0004). The previously-unscreened group decreased 28.6%, and the incidence rates within this group remained stable.

Conclusions

The increase in diabetes prevalence is decelerating despite declining mortality and increasing testing rates. A decline in previously-screened incident cases and a shrinking pool of previously-unscreened members suggests that diabetes trends in Israel are moving toward equilibrium, rather than a growing epidemic.

     

The prognostic value of troponin T and echocardiography in acute pulmonary edema

OBJECTIVE: Several studies documented the relevance of autonomic activity in the pathophysiology of heart failure. In our study we evaluated the adjustment of this activity under different stimuli, by means of heart rate variability (HRV), and correlated these findings with long-term mortality and sustained VT occurrence. PATIENTS AND METHOD: Fifty-three patients (mean age 54+/-9 years) with heart failure were submitted to time and frequency domain HRV analysis. This latter analysis was performed at rest, during paced breathing and during passive tilt. RESULTS: Lower standard deviation of RR intervals (76.76+/-24 versus 107.70+/-43, p=0.02), mean of the 5-min standard deviations of RR intervals (35.14+/-15 versus 62.39, p<0.01), standard deviation of the 5-min average RR intervals (69.42+/-19 versus 91.79+/-30, p=0.02), and baseline Low-Frequency (LF) power (15.15+/-12 versus 40.39+/-24 nu, p=0.001) characterized patients who died. Paced breathing induced a significant reduction of LF (40.39+/-24 to 20.12+/-18 nu, p<0.0001) and increase of High Frequency power (HF) (47.31+/-23 to 70.63+/-16 nu, p<0.0001) in survivors, while tilting induced a reduction of HF (47.31+/-23 to 29.80+/-16 nu, p<0.0001). Patients who died did not show significant variation of HRV neither during paced breathing nor during tilt. Reduced time domain indexes were significantly correlated to sustained VT occurrence. CONCLUSIONS: Patients with heart failure with a better prognosis are characterized by a responsiveness of autonomic modulation. Simple maneuvers, such as tilting and paced breathing, seem to provide more useful information, than the baseline evaluation of autonomic status, in identifying patients with a higher mortality. Time domain analysis was more helpful to estimate arrhythmic risk.     

Physical activity and cardiac function in the oldest old

The relationship of physical activity (PA) and cardiac function in the oldest old remains unclear. The objective of this study was to evaluate the relationship between PA and cardiac structure and function, in the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age homogeneous cohort of Jerusalem residents born in 1920-1921. A total of 496 of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. Standard echocardiographic assessment of cardiac structure and function including ejection fraction (EF) and diastolic function as assessed by E:E' measurements was performed. PA was defined as a dichotomous (≥4?hr of light exercise weekly) and as a categorical variable (<4?hr weekly/4 hours weekly/at least 1?hr daily/sport at least twice weekly). On bivariate analysis, mean EF was lower among sedentary versus active women (55.5%±8.5% vs. 58.4%±8.3, p=0.021). No other significant differences were observed between sedentary and active subjects, for either systolic or diastolic function. After adjusting for sex, education, diabetes, ischemic heart disease, hypertension, dependence in activities of daily living, and body mass index (BMI), no significant associations were found between systolic or diastolic function, or left ventricular structure and PA. Gender-specific analyses yielded similar findings. Our study of the oldest old did not demonstrate an association between PA and cardiac structure or function.     

Use of collagen-hydroxyethylmethacrylate hydrogels for cell growth.

Collagen-hydroxyethylmethacrylate hydrogels were prepared by polymerizing monomeric hydroxyethylmethacrylate in the presence of various concentrations of soluble native collagen. The resulting transparent hydrogels were evaluated as substrata for growth of IMR-90 human embryonic lung fibroblasts. Without collagen no significant growth occurred, whereas a dose-response curve expressing maximal cell growth against collagen concentration could be constructed quite readily by the use of appropriate hydrogels. The method allows for quantification of the collagen contribution to cell growth and, in a more general sense, provides the foundation for a relatively easy procedure to probe mechanisms of cell adhesion and cell differentiation.