Effect of repeated administration of prolactin releasing peptide on feeding behavior in rats

Prolactin releasing peptide (PrRP) has been reported to reduce food intake in rats. We tested the effect of i.c.v. administration of PrRP-31 on food intake in both food deprived and free-feeding rats. We did not find any effect of PrRP-31 on food intake after single injections of up to an 8-nmol dose, but observed a marked decrease in food intake and body weight in rats that received a repeated twice daily administration of 8 nmol of PrRP-31. This effect was associated with an adverse behavioral pattern, indicating that the repeated high doses of the peptide caused non-specific effects inducing anorexia. We also tested several other behavioral parameters like locomotion and exploratory time, grooming and resting time, using lower doses of PrRP that did not cause the adverse behavior. Moreover, we carried out locomotor and sensory motor activity tests at the doses that exerted the most pronounced effect on the food intake. None of these tests suggested any specific behavioral effect of PrRP. We conclude that the behavioral pattern induced by PrRP is likely to be different from those induced by many other neuropeptides affecting food intake in rats.     

The usefulness of adenosine 99mTc tetrofosmin SPECT for the diagnosis of left anterior descending coronary artery disease in patients with chest pain and left bundle branch block

OBJECTIVES: The aim of this study was to assess the usefulness of 99mTc tetrofosmin single photon emission computed tomography (SPECT) for the diagnosis of left anterior descending (LAD) coronary artery disease in 60 subjects with left bundle branch block (LBBB) admitted for chest pain. METHODS AND RESULTS: Adenosine 99mTc tetrofosmin SPECT, transthoracic echocardiogram and coronary angiography were performed, by protocol, in 60 non-infarcted consecutive patients. The mean left ventricular ejection fraction (LVEF) was 41.6 +/- 10.8%. A significant angiographic disease of the LAD was found in 15 (25%) patients. The sensitivity and the specificity of SPECT was found to be 75% and 89%, respectively; the positive predictive value (PPV) was 70% with a negative predictive value (NPV) of 91%. During the adenosine infusion the QRS complex width reduced from 131.3 +/- 29.6 ms to 125.5 +/- 28.6 ms in the patients without LAD involvement (P = 0.008) but remained unchanged in LAD disease patients (P = 0.1). Combining SPECT information and QRS analysis the sensitivity increased to 87% with unchanged specificity, the PPV was 74% and the NPV resulted 95%. At 2-year follow-up 13 (22%) patients experienced a cardiac event. Using Kaplan-Meier analysis, an LVEF of < or = 35% was the only predictor of cardiac events (P = 0.01, log-rank 6.2). CONCLUSIONS: A quarter of patients with LBBB complaining of chest pain had LAD coronary disease. The highly negative predictive value of adenosine SPECT could help in the exclusion of LAD disease, especially when the SPECT image is combined with the QRS analysis.     

Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708-2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1-related DOA.     

Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.     

Treatment of diabetic nephropathy in its early stages

Diabetic nephropathy is one of the most frequent causes of end-stage renal disease (ESRD), and, in recent years, the number of diabetic patients entering renal replacement therapy has dramatically increased. The magnitude of the problem has led to numerous efforts to identify preventive and therapeutic strategies. In normoalbuminuric patients, optimal glycemic control (HbA(1c) lower than 7.5%) plays a fundamental role in the primary prevention of ESRD [weighted mean relative risk reduction (RRR) approximately 37% for metabolic control versus trivial renoprotection for intensive anti-hypertensive therapy or ACE-inhibitors (ACE-I)]. In the microalbuminuric stage, strict glycemic control probably reduces the incidence of overt nephropathy (weighted mean RRR approximately 50%), while blood pressure levels below 130/80 mmHg are recommended according to the average blood pressure levels obtained in various studies. In normotensive patients, ACE-I markedly reduce the development of overt nephropathy almost regardless of blood pressure levels; in hypertensive patients, ACE-I are less clearly active (weighted mean RRR approximately 23% versus other drugs), whereas angiotensin-receptor blockers (ARB) appear strikingly renoprotective. Once overt proteinuria appears, it is uncertain whether glycemic control affects the progression of nephropathy. In type 1 diabetes, various anti-hypertensive treatments, mainly ACE-I, are effective in slowing down the progression of nephropathy; in type 2 diabetes, two recent studies demonstrate that ARB are superior to conventional therapy or calcium channel blockers (CCB). In clinical practice, pharmacological tools are not always used to the best benefit of the patients. Therefore, clinicians and patients need to be educated regarding the renoprotection of drugs inhibiting the renin-angiotensin system (RAS) and the overwhelming importance of achieving target blood pressure.     

Effect of surface finishing and storage media on bi-axial flexure strength and microhardness of resin-based composite

This in vitro study tested the following null hypotheses: (1) surface finishing treatments do not significantly affect the biaxial flexure strength and microhardness of resin-based composites (RBC) and (2) storage media do not significantly affect these physical properties. Discs (81 RBC and 81 UR; 3M/ESPE) were prepared using a circular polyethylene mold (2.4-mm thick x 16.7 mm in diameter) that was polymerized through a Mylar strip and divided into three surface finishing treatment groups: 1 microm aluminum oxide slurry; 15 microm diamond and a Mylar strip. Randomly selected controls for each finishing group were stored at room temperature in individual vials. Test specimens were immersed in water, stored at 37 degrees C for two days and transferred for an additional seven days to one of three aqueous storage media at 37 degrees C: coffee (pH 5.1), cola (pH 2.4) or red wine (pH 3.7). Post immersion (nine days total), the specimens were tested for biaxial flexure strength (BFS) and Vicker's microhardness (VHN). ANOVA and Tukey's HSD test were used for statistical analysis. ANOVA results indicated that surface finishing treatments had a significant effect on the biaxial flexure strength and microhardness of the RBC and the UR specimens. BFS results for RBC specimens were AL>DD>ML (p<0.0001) and VHN results were AL, DD>ML (p<0.0001). Storage in wine medium reduced the VHN of UR specimens significantly. Both alternative hypotheses were accepted. In addition, the Mylar finishing group, because of the resin-rich surface layer, yielded the lowest mean values of BFS and VHN.