The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress.

Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

Identification of sarcopenia and dynapenia in CKD predialysis patients with EGWSOP2 criteria: An observational, cross-sectional study.

OBJECTIVES: Using the new European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, we identified sarcopenic and dynapenic patients in a cohort of predialysis patients with chronic kidney disease (CKD), and evaluated their clinical and laboratory characteristics. METHODS: The study population consisted of 85 (55 men) clinically stable predialysis CKD patients (92.9% in stages 3-5), with a median age of 65.0 (52.5-72.0) y. We classified as sarcopenic the patients with handgrip strength (HGS) and muscle mass both lower than the respective EWGSOP2 cutoff values and as dynapenic those in whom only HGS was less than these reference values. HGS was measured with a hand dynamometer, whereas muscle mass was measured by bioimpedance analysis. Renal function was evaluated as Modification of Diet in Renal Disease estimated glomerular filtration rate. RESULTS: The prevalence of sarcopenia and dynapenia was, respectively, 7.1% and 17.6%. As reported in previous studies, serum albumin and hemoglobin were lower in sarcopenic patients than in patients with preserved muscle mass and strength. However, unlike in these studies, sarcopenia prevalence did not increase with CKD stage, and estimated glomerular filtration rate was similar between groups. Moreover, no difference was identified in any of the aforementioned parameters between dynapenic patients and patients with preserved muscle mass and strength. CONCLUSIONS: The EWGSOP2 criteria identified sarcopenia in CKD with a prevalence similar to previous diagnostic criteria. In addition, they found that dynapenia was highly prevalent. Nevertheless, the EWGSOP2 criteria could be better adapted to CKD patients to improve their ability to detect high-risk sarcopenic and dynapenic patients.

Prevalence of obesity and obesity-associated muscle wasting in patients on peritoneal dialysis.

BACKGROUND AND AIMS: A progressive decrease in muscle mass until full-blown sarcopenia may occur in patients on peritoneal dialysis (PD) and worsen their life quality and expectancy. Here we investigate the prevalence of obesity and obesity-associated muscle wasting in PD patients. PATIENTS AND METHODS: The study design was observational, cross sectional. Body composition was assessed with BIA and BIVA in 88 PD patients (53.4 ± 13.1 years; 67% male). Patients with obesity and/or with reduced muscle mass were identified using FMI and SM/BW cutoff values, respectively. Inflammatory status was assessed by measuring CRP and fibrinogen blood levels. RESULTS: A total of 44.3% of the patients showed a reduced muscle mass (37.5% moderate and 6.8% severe). The prevalence of obesity was 6.1%, 81.8%, and 100% in patients with normal, moderately, and severely reduced muscle mass, respectively (p < 0.05). Of the total, 15.2% of the patients with normal muscle mass, 18.4% of those with moderately reduced muscle mass, and 66.7% of those with severely reduced muscle mass had diabetes. The prevalence of severe muscle mass loss was higher in those with diabetes than in those without diabetes (22.2% vs. 2.8%, p < 0.05). Patients with obesity-associated muscle wasting showed higher fibrinogen (613.9 ± 155.1 vs. 512.9 ± 159.5 mg/dL, p < 0.05) and CPR (1.4 ± 1.3 vs. 0.6 ± 0.8 mg/dL, p < 0.05) blood concentrations than those with normal body composition. CONCLUSION: Obesity and diabetes were strongly associated with muscle mass loss in our PD patients. It remains to be established whether prevention of obesity with nutritional interventions can halt the occurrence of muscle mass loss in patients on PD.

Effect of a Short-Course Treatment with Synbiotics on Plasma p-Cresol Concentration in Kidney Transplant Recipients.

OBJECTIVE: We evaluated whether a short-term course with synbiotics may lower plasma p-Cresol concentrations in kidney transplant patients (KTRs) who accumulate this uremic toxin both because of increased production by their dysbiotic gut microbiome and because of reduced elimination by the transplanted kidneys. METHODS: Thirty-six KTRs (29 males, mean age 49.6 ± 9.1 years) with transplant vintage > 12 months, stable graft function, and no episode of acute rejection or infection in the last 3 months were enrolled in this single-center, parallel-group, double-blinded, randomized (2:1 synbiotic to placebo) study. Synbiotic (Probinul Neutro, CadiGroup, Rome, Italy) or placebo was taken at home for 30 days, as 5 g powder packets dissolved in water three times a day far from meals. The main outcome measure was the decrease in total plasma p-Cresol measured by high-performance liquid chromatography at baseline and after 15 and 30 days of placebo or synbiotic treatment. RESULTS: After 15 and 30 days of treatment, plasma p-Cresol decreased by 40% and 33% from baseline (both p < 0.05), respectively, in the synbiotic group, whereas it remained stable in the placebo group. After 30 days of treatment, no significant change was observed in either group in renal function, glycemia, plasma lipids, or albumin concentration. Treatment was well tolerated and did not induce any change in stool characteristics. CONCLUSION: The results of this pilot study suggest that treatment with synbiotics may be effective to lower plasma p-Cresol concentrations in KTRs. Prospective larger scale, longer term studies are needed to establish whether cardiovascular prognosis could also be improved with this nutritional intervention.

Utilization of antihypertensive drugs in obesity-related hypertension: a retrospective observational study in a cohort of patients from Southern Italy.

BACKGROUND: Although the pathophysiological mechanisms of arterial hypertension are different in obese and lean patients, hypertension guidelines do not include specific recommendations for obesity-related hypertension and, therefore, there is a considerable uncertainty on which antihypertensive drugs should be used in this condition. Moreover, studies performed in general population suggested that some antihypertensive drugs may increase body weight, glycemia and LDL-cholesterol but it is unclear how this impact on drug choice in clinical practice in the treatment of obese hypertensive patients. Therefore, in order to identify current preferences of practitioners for obesity-related hypertension, in the present work we evaluated antihypertensive drug therapy in a cohort of 129 pharmacologically treated obese hypertensive patients (46 males and 83 females, aged 51.95 ± 10.1 years) that came to our observation for a nutritional consultation. METHODS: Study design was retrospective observational. Differences in the prevalence of use of the different antihypertensive drug classes among groups were evaluated with χ(2) square analysis. Threshold for statistical significance was set at p < 0.05. RESULTS: 41.1 % of the study sample was treated with one, 36.4 % with two and the remaining 22.5 % with three or more antihypertensive drugs. In patients under single drug therapy, ß-blockers, ACEIs and ARBs accounted each for about 25 % of prescriptions. The prevalence of use of ß-blockers was about sixfold higher in females than males. Diuretics were virtually never used in monotherapy regimens but were used in more than 60 % of patients on dual antihypertensive therapy and in all patients assuming three or more drugs. There was no significant difference in the prevalence of use of any of the aforementioned drugs among patients with obesity of type I, II and III or between patients with or without metabolic syndrome. CONCLUSIONS: Our data show that no first choice protocol seems to be adopted in clinical practice for the treatment of obesity-related hypertension. Importantly, physicians do not seem to differentiate drug use according to the severity of obesity or to the presence of metabolic syndrome or to avoid drugs known to detrimentally affect body weight and metabolic profile in general population.

Energy-restricted, n-3 polyunsaturated fatty acids-rich diet improves the clinical response to immuno-modulating drugs in obese patients with plaque-type psoriasis: a randomized control clinical trial.

BACKGROUND & AIMS: Low-grade systemic inflammation associated with obesity may worsen the clinical course of psoriasis. This study aimed to assess the effectiveness of an energy-restricted diet, enriched in n-3 polyunsaturated fatty acids (PUFAs) and poor in n-6 PUFAs, on metabolic markers and clinical outcome of obese patients with psoriasis. METHODS: Forty-four obese patients with mild-to-severe plaque-type psoriasis treated with immuno-suppressive drugs were randomized to assume for six months either their usual diet or an energy-restricted diet (20 kcal/kg/ideal body weight/day) enriched of n-3 PUFAs (average 2.6 g/d). All patients continued their immuno-modulating therapy throughout the study. RESULTS: At 3 and 6 months, a significant clinical improvement was observed in patients assuming the low-calorie high n-3 PUFAs diet respect to controls. Specifically Psoriasis Area Score Index (7.7 ± 3.7, 5.3 ± 4.3 and 2.6 ± 3.0, respectively; p < 0.05), itch scores (15.4 ± 13.5, 12.3 ± 12.1 and 1.8 ± 5.9, respectively; p < 0.05) and Dermatological Life Quality Index (19.5 ± 1.9, 11.4 ± 3.5 and 5.1 ± 1.6; respectively, p < 0.05) all decreased respect to baseline. In these subjects but not in controls, a significant decrease in body weight (93.8 ± 10.1, 85.8 ± 11.4 and 83.1 ± 12.1 kg, respectively; p < 0.05), waist circumference (112.7 ± 7.2, 106.1 ± 10.3 and 101.9 ± 10.4 cm; p < 0.05), serum triglycerides (141.8 ± 51.1, 100.5 ± 26.6 and 90.2 ± 34.5 mg/dL; respectively, p < 0.05), serum total cholesterol (198.3 ± 31.7, 171.4 ± 29.0 and 176.5 ± 20.5 mg/dL; respectively, p < 0.05) and n-6/n-3 ratio intake also occurred (5.1 ± 0.9, 2.0 ± 0.9 and 2.3 ± 1.1; respectively, p < 0.05). CONCLUSIONS: In obese psoriatic patients, an energy-restricted diet designed to increase n-3 and reduce n-6 PUFAs, ameliorated the metabolic profile and, by increasing the response to immuno-modulating therapy, improved the clinical outcomes of the disease (ClinicalTrials.gov identifier: NCT01876875).

Dietary intake as a link between obesity, systemic inflammation, and the assumption of multiple cardiovascular and antidiabetic drugs in renal transplant recipients.

We evaluated dietary intake and nutritional-inflammation status in ninety-six renal transplant recipients, 7.2 ± 5.0 years after transplantation. Patients were classified as normoweight (NW), overweight (OW), and obese (OB), if their body mass index was between 18.5 and 24.9, 25.0 and 29.9, and ≥ 30 kg/m(2), respectively. Food composition tables were used to estimate nutrient intakes. The values obtained were compared with those recommended in current nutritional guidelines. 52% of the patients were NW, 29% were OW, and 19% were OB. Total energy, fat, and dietary n-6 PUFAs intake was higher in OB than in NW. IL-6 and hs-CRP were higher in OB than in NW. The prevalence of multidrug regimen was higher in OB. In all patients, total energy, protein, saturated fatty acids, and sodium intake were higher than guideline recommendations. On the contrary, the intake of unsaturated and n-6 and n-3 polyunsaturated fatty acids and fiber was lower than recommended. In conclusion, the prevalence of obesity was high in our patients, and it was associated with inflammation and the assumption of multiple cardiovascular and antidiabetic drugs. Dietary intake did not meet nutritional recommendations in all patients, especially in obese ones, highlighting the need of a long-term nutritional support in renal transplant recipients.

Role of dietary intervention and nutritional follow-up in heart transplant recipients.

BACKGROUND: Obesity, dyslipidemia, hypertension, and diabetes mellitus are common features after heart transplantation and they lead to coronary artery disease and graft loss. AIM: To determine the effects of a dietary intervention on nutritional status and metabolic outcome of two groups enrolled during or after the first year from the transplant. METHODS: Forty two subjects (mean age 51.36+/-12.4 yr) were studied; 20 were enrolled during the first year by the transplant, 22 were enrolled after the first year from the transplant (7.9+/-3.86 and 56.86+/-38.6 months after surgery, respectively). According to diet compliance both groups were divided into two subgroups and they were prospectively followed for 4 years. Anthropometric measurements, biochemical nutritional markers, and dietary records were collected at baseline (T0) and after a 12-month follow-up period (T12) and a 48-month follow-up period (T48). Body composition was performed at T0 and T12. RESULTS: Diet compliance was associated with a decrease in total cholesterol, triglycerides and glucose plasma level and with a weight loss mainly due to a decrease in fat mass. CONCLUSION: Our study shows the efficacy of dietary intervention to obtain an early and late weight and metabolic control after heart transplant.

Body mass index and bioelectrical vector distribution in 8-year-old children.

OBJECTIVE: To describe bioelectrical impedance vector distribution in relation to BMI (body mass index; body weight/stature(2)) in a population of healthy children in order to detect possible changes in body composition status. DESIGN: Observational study involving 464 healthy 8-year-old children. The subjects were divided into three groups based on their BMI: 218 normal weight (NW) children with BMI<18.4 for male and BMI<18.3 for female; 135 overweight (OW) children with BMI 18.4 to <21.6 for male and with BMI 18.3 to <21.6 for female; 111 obese (OB) children with BMI>/=21.6. Skinfold thickness was measured at the triceps using a Holtain caliper. Bioelectrical impedance analysis (BIA) measurements were performed. Total body water (TBW), fat-mass (FM), fat-free mass (FFM), body cell mass (BCM) and extra-cellular water (ECW) were estimated using conventional BIA regression equations. The resistance-reactance graph (RXc graph) method was used for vector BIA using as reference population the set of 353 children with BMI 14.0-21.5kg/m(2). RESULTS: Mean vector displacement followed a definite pattern, with progressive vector shortening in groups with increasing BMI class, and along a fixed phase angle. This pattern indicates an increase in TBW due to an increase in soft tissue mass with an average, normal hydration. In NW children, vectors out of the right and upper half of the 75% tolerance ellipse indicating leanness, and vectors falling out of the right and lower half of the tolerance ellipse indicating undernutrition, show a significantly reduced value of BCM but no significant differences in FM or triceps skinfold thickness (TST), respectively, compared to vectors falling within the 75% tolerance ellipse. CONCLUSIONS: Although BMI is a reliable measure to grade overweight, it cannot differentiate whether weight change is due to variation of FM, FFM or water. In our study a different impedance vector pattern has been associated with normal weight to obesity, and we have established the trajectory followed by the impedance vector of standardized age, healthy children grouped by BMI. This BIVA may be useful for clinical purposes due to ability to detect changes in hydration or body composition in children.

Role of dietary intervention on metabolic abnormalities and nutritional status after renal transplantation.

BACKGROUND: In these last years, several traditional risk factors for cardiovascular disease, like obesity, dyslipidaemia, hypertension and post-transplant diabetes mellitus have been also identified as important non-immunological risk factors leading to the development of chronic allograft nephropathy, the first cause of graft loss in transplanted patients. The aim of the present study was to determine the effects of a 12-month dietary regimen on the nutritional status and metabolic outcome of renal transplant recipients in the first post-transplant year. METHODS: Forty-six cadaver-donor renal transplant recipients (mean age 40.8 +/- 10.1-years), enrolled during the first post-transplant year (4.8 +/- 3.3 months) and followed prospectively for a 12 month period. Biochemical and nutritional markers, anthropometric measurements, body composition (by conventional bioelectrical impedance analysis) and dietary records (using a detailed food-frequency questionnaire) at baseline and after 12 months. RESULTS: Compliance to the diet was related to sex (male better than female) and was associated with weight loss primarily due to a decrease in fat mass, with decrease in total cholesterol and glucose plasma levels and with a concomitant rise in serum albumin. CONCLUSION: After renal transplantation, health benefits of proper metabolic balance that include reduced body fat, weight loss, lower cholesterol and triglycerides levels and an improvement, fasting glucose levels can be obtained when dietary intervention occurred.

Bioelectrical impedance analysis and age-related differences of body composition in the elderly.

BACKGROUND AND AIM: Significant changes in body composition that have important health related effects may occur in the elderly. In this study, we evaluated the bioelectrical characteristics in a large group of apparently healthy Caucasian men in the age range 50-80 years, as a function of age and body mass index. METHODS: We studied 315 men with ages ranging from 50 to 80 years. They were divided into three groups according to body mass index (kg/m(2)): 18.5-24.9 normoweight (NW); 25.0-29.9 overweight (OW); > or =30 obese (OB), and they were classified in nine age subgroups: 50-59 (young-old, YO); 60-69 (old, O); 70-80 (oldest, OS). Fat-free mass, fat mass and body cell mass were investigated using conventional bioelectrical impedance analysis. Body composition was also assessed by bioelectrical impedance vector analysis and the RXc graph method. RESULTS: Body cell mass decreased significantly with age particularly in subgroups of the OW and OB groups (p<0.05). Mean vector displacement followed a definite pattern, with downward migration of the ellipses in the OW and OB groups, after 70 years of age. CONCLUSIONS: Ageing was associated with a pattern of vector bioelectrical impedance analysis indicating decreased soft tissue mass (fat-free mass and body cell mass), particularly in OW and OB-OS healthy men. We suggest 70 years of age as a cut-off for significant quantitative and qualitative (tissue electrical properties) body composition modifications. This bioelectrical impedance vector analysis pattern associated with ageing and across the different body mass index categories, may be useful for clinical purposes and can be used in geriatric routine to accurately assess the body composition modifications occurring in the elderly.

Laparoscopic gastric banding and body composition in morbid obesity.

BACKGROUND AND AIM: Gastric banding induced considerable and rapid weight loss in morbid obesity. Nevertheless data on changes in body composition following gastric banding are scanty. In this study, we evaluated the 2-year changes in body composition in a small group of morbidly obese women treated by laparoscopic adjustable gastric banding (LAGB) associated with a well balanced low-calorie diet. METHODS AND RESULTS: We studied 20 premenopausal morbid obese women with BMI ranging from 35 to 57 (kg/m2) before, and 6, 12 and 24 months after laparoscopic adjustable gastric banding (LAGB). A well balanced 5.4 MJ/day hypocaloric diet was prescribed after surgery. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were investigated using conventional bioelectrical impedance analysis (BIA). Tissue hydration was also assessed by impedance vector analysis and the RXc graph method. The subjects showed a total weight loss of 28% of baseline body weight. In the first 6 months after surgery, patients lost 18.5+/-5.9 kg of body weight (17.6+/-6.2 kg of FM and 0.7+/-1.4 kg of FFM). From 6 to 12 months, a further 12.5+/-7.5 kg of body weight was lost (10.5+/-8.2 kg of FM and 2.2+/-3.8 kg of FFM). During the last 12 months, weight loss was 3.0+/-2.3 kg (1.9+/-3.7 kg of FM and 1.1+/-2.9 kg of FFM). The weight loss observed after LAGB was mainly due to a decrease in FM, whereas TBW, FFM and BCM were only slightly and non-significantly reduced. No changes in body hydration status were observed after surgery. CONCLUSIONS: LAGB associated with a well balanced low-calorie diet achieved a satisfactory 2-year weight loss, while sparing FFM and not causing body fluid alterations.

Body composition and cardiovascular risk factors in pretransplant hemodialysis patients.

BACKGROUND: Obesity, hyperlipemia and cardiovascular complications contribute to a significant proportion of morbidity and mortality of renal transplant patients and have negative effects on renal survival. Aim of the present study was to evaluate the main abnormalities in body composition and the prevalence of some cardiovascular risk factors in a population of hemodialyzed (HD) patients awaiting renal transplantation. METHODS: We studied 151 HD patients, all included in a waiting list for renal transplantation, 97 males and 54 females, with mean age 47.4+/-12 years. Patients were divided into three groups according to their body mass index (BMI) (kg/m2): 18.5 to 24.9 (normoweight, NW); 25.0 to 29.9 (overweight, OW); > or =30 (obese, OB). The body composition measurements were obtained the day after the mid-week HD session using bioelectrical impedance analysis (BIA). RESULTS: We found that 47 patients were NW (31%), while 56 were OW (37%), and 48 were OB (32%). BIA-measured body cell mass was (BCM) significantly increased in the OW as compared with the NW group (P<0.001), but, of note, no significant difference was found in OB group in comparison with the OW. Total cholesterol and triglycerides plasma levels were significantly elevated in OW and OB patients with respect to NW (P<0.05) and an increased prevalence of diabetes was seen in OB patients (NW: 6%, OW: 5%, OB: 12%). CONCLUSIONS: These data show that a large proportion of patients awaiting renal transplant are overweight or obese and a consistent part of them have other cardiovascular risk factors associated. Furthermore, obese HD patients have a BCM lower than predicted on the basis of BMI and show an altered metabolic profile. A better understanding of the characteristics of patients included in the renal transplant waiting list is crucial in order to design prospective studies that aim to define the proper risk profile for the selection of patients.