Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study

Background Feline nonflea hypersensitivity dermatitis (NFHD) is a frequent cause of over-grooming, scratching and skin lesions. Multimodal therapy often is necessary. Hypothesis/Objectives To investigate the efficacy of ultramicronized palmitoylethanolamide (PEA-um) in maintaining methylprednisolone-induced remission in NFHD cats. Animals Fifty-seven NFHD cats with nonseasonal pruritus were enrolled originally, of which 25 completed all study requirements to be eligible for analysis. Methods and materials Cats were randomly assigned to PEA-um (15 mg/kg per os, once daily; n = 29) or placebo (n = 28) while receiving a 28 day tapering methylprednisolone course. Cats responding favourably to methylprednisolone were then administered only PEA-um (n = 21) or placebo (n = 23) for another eight weeks, followed by a four week long treatment-free period. Cats were maintained in the study until relapse or study end, whichever came first. Primary outcome was time to relapse. Secondary outcomes were pruritus Visual Analog Scale (pVAS), SCORing Feline Allergic Dermatitis scale (SCORFAD) and owner Global Assessment Score (GAS). Results Mean relapse time was 40.5 days (+/- 7.8 SE) in PEA-um treated cats (n = 13) and 22.2 days (+/- 3.7 SE) for placebo (n = 12; P = 0.04). On Day 28, the severity of pruritus was lower in the PEA-um treated cats compared to placebo (P = 0.03). Mean worsening of pruritus at the final study day was lower in the PEA-um group compared to placebo (P = 0.04), whereas SCORFAD was not different between groups. Mean owner GAS at the final study day was better in the PEA-um than the placebo-treated group (P = 0.05). Conclusion and clinical importance Ultramicronized palmitoylethanolamide could represent an effective and safe option to delay relapse in NFHD cats

Plasma homocysteine levels and cardiovascular mortality in patients with end-stage renal disease

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis in patients with normal renal function. Plasma homocysteine (Hcy) is increased in patients with chronic renal failure (CRF) and could be linked to their high cardiovascular (CV) morbidity and mortality. We prospectively studied 77 patients (47 males and 30 females aged 62.85 \ub1 1.53 yrs) who had been on maintenance hemodialysis (HD) (4 hr/ 73/week) for 65.5 \ub1 7.23 months. Patients were followed-up for 44 months. At baseline, blood samples were taken for hemoglobin (Hb), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, serum calcium, serum phosphates, parathyroid hormone (PTH), Hcy, vitamin B12, serum and erythrocyte folate and methylentetrahydrofolate-reductase (t-MTH-FR) genotype determination. Plasma Hcy levels of patients were divided into four quartiles. The univariate analysis demonstrated a significant relationship between Hcy and diastolic blood pressure (BP) (r=0.45; p=0.003), and both plasma (r=-0.30; p=0.03) and erythrocyte (r=-0.48; p=0.01) folate levels and CV score (r=0.39; p=0.007). Kaplan-Meier analysis showed that the mortality rate due to CV events was statistically significantly higher in the 4th Hcy quartile (68%; 12 patients) vs. the 3rd quartile (12%; two patients), the 2nd quartile (28%; four patients) and the 1st quartile (14%; two patients) (log-rank test p=0.02). Cox's regression analysis for CV survival showed that Hcy was a positive CV mortality predictor (\u3b2=0.02; hazard ratio=1.031; 95% confidence interval (95% CI): 1.013-1.050; p=0.001), while LDL cholesterol and albumin related negatively to CV mortality (LDL cholesterol: \u3b2=-0.02; hazard ratio=0.095; 95% CI: 0.0957-0.0997; p=0.035; albumin: P=-2.35; hazard ratio=0.097; 95% CI: 0.011-0.847; p=0.026). Our results show that Hcy is a strong independent mortality predictor in HD patients with a 3% increase in mortality for each 1 \u3bcmol/L increase in plasma Hcy concentration. This agrees with previous findings confirming the role of Hcy in predicting CV risk factors in uremic patients

Behaviour of regional adrenergic outflow in mild-to-moderate renal failure

OBJECTIVES: Chronic renal failure is characterized by a marked sympathetic activation. No information exists, however, as to whether the adrenergic overdrive is confined to selected vascular districts or is rather generalized to the whole cardiovascular system. METHODS: In 15 patients aged 60.5 \ub1 2.0 years (mean \ub1 SEM) with stable chronic renal failure belonging to stage 2-3 of the Kidney Foundation classification and in 12 age-matched healthy controls, we measured arterial blood pressure (Finapres), heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography) and postganglionic sympathetic nerve traffic in skeletal muscle and skin areas (microneurography). Muscle and skin nerve traffic measurements were made in a randomized sequence over two periods of 30 min each, spaced by a 20-30-min interval. Measurements also included evaluation of skin sympathetic responses to emotional stimuli. RESULTS: Muscle sympathetic nerve traffic was markedly and significantly greater in renal failure patients compared with controls (58.2 \ub1 3.6 vs. 36.8 \ub1 5.7 bursts/100 heart beats, P < 0.01), with this also being the case for plasma norepinephrine (380.6 \ub1 63 vs. 210.8 \ub1 29 pg/ml, P < 0.05). By contrast, skin sympathetic nerve traffic was superimposable in the two groups (11.5 \ub1 0.8 vs. 12.7 \ub1 1.7 bursts/minute, P = not significant), this being the case also for the responses to emotional arousal. CONCLUSION: These data provide the first evidence that the sympathetic activation characterizing renal failure is not generalized to the entire cardiovascular system. This may depend on the fact that the two sympathetic districts are governed by mechanisms that are differently affected by the chronic uraemic state

Role of vitamin E-coated membrane in reducing advanced glycation end products in hemodialysis patients: a pilot study

INTRODUCTION: Advanced glycation end products (AGEs) are markers of oxidative stress. AIMS: To assess if a vitamin-E-coated dialyzer affects plasma AGE levels and endothelial function in hemodialysis patients. METHODS: 16 patients were dialyzed with a synthetic modified cellulose membrane (SMC, n = 8) or a vitamin E-coated dialyzer (n = 8), respectively. At week 32 endothelial function was determined as brachial artery flow-mediated dilatation (FMD). Total AGEs, free pentosidine (FP), protein-bound pentosidine (BP) and autoantibodies against oxidized LDL (ox-LDL-autoantibodies) were assessed at baseline (T0) and at 16, 32, 40 and 42 weeks (T16, T32, T40 and T42). RESULTS: At T16 and T32 FP and BP were lower in vitamin E than in SMC (T 16: 88.7 +/- 8.96 vs. 124.2 +/- 11.90 pmol/ml plasma; p = 0.04, and 22.9 +/- 2.99 vs. 32.8 +/- 2.98 pmol/mg proteins; p = 0.04. T32: 78.7 +/- 8.54 vs. 123.7 +/- 10.15 pmol/ml plasma; p = 0.007, and 19.9 +/- 2.0 vs. 33.67 +/- 2.41 pmol/mg proteins; p = 0.001). In vitamin E, AGEs were lower at T32, T40 and T42 (946.7 +/- 80.91 vs. 1,351.2 +/- 179.33 AU/ml, p = 0.05; 986.9 +/- 59.63 vs. 1,509.9 +/- 154.17 AU/ml, p = 0.013; 890.3 +/- 73.70 vs. 1,453.9 +/- 153.16 AU/ml, p = 0.009). At T32 AGEs, ox-LDL autoantibodies and FMD were inversely correlated (R = -0.70 p = 0.007 and R = -0.59, p = 0.04, respectively). CONCLUSIONS: Vit E-coated membrane reduces plasma AGEs levels and AGEs values are negatively correlated with FM