Neuroanatomical specificity of prolactin-induced hyperphagia in virgin female rats

Intracerebroventricular (i.c.v.) administration of PRL increases food intake in virgin female rats but the brain site(s) at which PRL acts to promote feeding behavior is not known. The present studies investigated the role of the paraventricular nucleus (PVN), ventromedial nucleus (VMH), and medial preoptic nucleus (MPOA) in the hyperphagic actions of PRL. Ad-libitum-fed virgin female rats received twice daily site-specific injections of PRL (800 ng) over a period of 10 days. Only subjects demonstrating regular vaginal cyclicity were included in the study. Food intake, body weight, and vaginal cyclicity were measured daily. Results showed that PRL significantly increased food intake when injected into the PVN. A nonsignificant trend towards a hyperphagic response in the last 5 days of testing was observed in rats receiving intra-VMH injections of PRL, and the MPOA was not responsive to the feeding-stimulating properties of PRL. None of the manipulations affected body weight or vaginal cyclicity as demonstrated by vaginal smears. In sum, the present results reveal that one brain site at which PRL acts to increase food intake is the PVN, but these studies do not rule out the possibility that the effects of PRL on food intake may also involve other brain areas.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.     

Short-term influences of dichloroacetate on genetically hyperlipemic rats

The effects of short-term (7 days) administration of dichloroacetate (DCA) on carbohydrate and lipid metabolism in the Zucker obese and lean rat were investigated. Metabolic effects of the drug were more pronounced in the obese than in the lean rat. DCA decreased fasting blood glucose concentrations in both lean and obese rats, but more so in the fat animals, probably because of higher initial levels. The hypoglycemic action of DCA is likely attributable to a direct effect on liver and peripheral tissues and not to an indirect action caused by a decrease in the glucagon-to-insulin ratio because the drug induced just the opposite effect. DCA decreased plasma triglycerides (TG) and free fatty acids (FFA) in the hyperlipemic rats but not in lean rats. Intrahepatic triglyceride content diminished after drug treatment in fat rats, suggesting decreased hepatic TG synthesis. Hyperketonemia, induced in both lean and fat rats by DCA treatment, was also greater in the obese animal. This response was probably caused by accelerated hepatic ketone body production due to increased β-oxidation, and not to enhance FFA substrate supply. These data demonstrate that DCA is capable of correcting many of the underlying abnormalities in carbohydrate and fat metabolism in the obese Zucker rat.     

Diaphragmatic Hernia Masquerading as a Pulmonary Metastasis

Iatrogenic injury accounts for the second most common cause of acquired diaphragmatic hernias after penetrating trauma. An increased incidence of these hernias has been observed with the widespread use of laparoscopic surgery. We present the case of a 65-year-old woman who initially underwent sigmoid resection for an adenocarcinoma and a subsequent liver resection for metastasis. She was noted to have a left lower lobe pulmonary nodule on surveillance computed tomography, for which she underwent a mini-thoracotomy for a planned resection. At the time of surgery, the pulmonary nodule was discovered to be a diaphragmatic hernia, most probably of iatrogenic origin. We discuss the difficulty in diagnosis given her history and the location of such a lesion.     

Energy landscape analysis of native folding of the prion protein yields the diffusion constant, transition path time, and rates

Protein folding is described conceptually in terms of diffusion over a configurational free-energy landscape, typically reduced to a one-dimensional profile along a reaction coordinate. In principle, kinetic properties can be predicted directly from the landscape profile using Kramers theory for diffusive barrier crossing, including the folding rates and the transition time for crossing the barrier. Landscape theory has been widely applied to interpret the time scales for protein conformational dynamics, but protein folding rates and transition times have not been calculated directly from experimentally measured free-energy profiles. We characterized the energy landscape for native folding of the prion protein using force spectroscopy, measuring the change in extension of a single protein molecule at high resolution as it unfolded/refolded under tension. Key parameters describing the landscape profile were first recovered from the distributions of unfolding and refolding forces, allowing the diffusion constant for barrier crossing and the transition path time across the barrier to be calculated. The full landscape profile was then reconstructed from force-extension curves, revealing a double-well potential with an extended, partially unfolded transition state. The barrier height and position were consistent with the previous results. Finally, Kramers theory was used to predict the folding rates from the landscape profile, recovering the values observed experimentally both under tension and at zero force in ensemble experiments. These results demonstrate how advances in single-molecule theory and experiment are harnessing the power of landscape formalisms to describe quantitatively the mechanics of folding.     

Nutritional intake and oxidative stress in chronic heart failure

Background and aimsPatients with chronic heart failure (CHF) are known to be at risk of malnutrition, and cardiac cachexia is an adverse prognostic indicator. The aim of this study was to determine the dietary adequacy of CHF patients compared with Dietary Reference Values, to compare the nutritional intake and status of CHF patients to a healthy comparison group, and finally to determine whether nutritional intake and status depended on New York Heart Association (NYHA) functional class.Methods and ResultsPatients with CHF (n = 39) and a comparison group of 27 healthy participants, who did not have CHF, were asked to complete a four-day food diary, and energy and nutrient intakes were calculated. F_2α-isoprostanes were measured in urine as an indicator of oxidative stress and antioxidants were measured in serum or plasma. Overall 73% of the CHF patients were consuming less than recommended energy intakes, and more than 50% of these patients were also consuming less than recommended vitamin D, selenium and zinc intakes. Nutrient intake (energy, vitamin B6, D, E, iron, folate and riboflavin) was lower in CHF patients than in the comparison group, with vitamin B6 and folate intake and antioxidant status decreasing, and isoprostane status increasing as NYHA functional class increased.ConclusionThe majority of CHF patients do not meet dietary reference values for energy and a range of nutrients, and nutrient intake is lower in CHF patients than in healthy individuals. Dietary inadequacy tends to be increased in those with more severe disease.     

Mitral valve prolapse in eating and panic disorder: A pilot study

The prevalence of echocardiographic mitral valve prolapse (MVP) and arrhythmias was studied in controls (n = 23) and patients with panic disorder (n = 14), bulimia nervosa (n = 14), and anorexia nervosa (n = 21). There was approximately twice the rate of MVP in patient groups compared to controls, a statistically insignificant difference. Importantly, the presence of prolapse was not associated with measures of weight or depression but there was a trend for MVP to be associated with anxiety disorder in bulimic patients. There were no significant arrhythmias found. These results raise the possibility that MVP may not be a state weight-related phenomenon as has been proported, but rather a trait phenomenon reflecting comorbidity with anxiety disorder.