Combined use of handgrip strength and hemoglobin as markers of undernutrition in patients with stage 3-5 chronic kidney disease.

BACKGROUND AND AIMS: The early identification of undernourished patients with CKD could help instating appropriate nutritional intervention before the full development of the threatening condition known as Protein Energy Wasting (PEW). Handgrip strength (HGS) and blood hemoglobin (Hb) concentration are two parameters considered representative of nutritional status but not included among the criteria for PEW diagnosis. In the present work we investigated whether they could help identifying CKD patients at risk of undernutrition. METHODS AND RESULTS: We performed a two-step cluster analysis to classify a cohort of 71 stage 3-5 CKD patients, none of which with PEW, according to their Hb concentration and dominant-hand HGS. Two clusters were finely separated using this method. When we compared the two groups for main body composition and nutritional variables by using t-test statistics or Mann-Whitney test, as appropriate, we found significant differences in PhA, ECW/TBW, ASMI, serum iron. Then we stratified our population by gender and performed cluster analysis as well. PhA, ECW/TBW were still significantly different in the two clusters both in M and in F, while serum iron concentration only in males and ASMI only in females. CONCLUSION: These results suggest that either in male than in female Hb concentration and HGS may distinguish two subgroups of CKD patients with different nutritional status and disease severity. Patient belonging to either of these cluster can be easily identified by using the HGS/Hb ratio which represents the HGS normalized per gr Hb.

Dietary Polyphenols, Microbiome, and Multiple Sclerosis: From Molecular Anti-Inflammatory and Neuroprotective Mechanisms to Clinical Evidence.

Multiple sclerosis (MS) is a multifactorial, immune-mediated disease caused by complex gene-environment interactions. Dietary factors modulating the inflammatory status through the control of the metabolic and inflammatory pathways and the composition of commensal gut microbiota, are among the main environmental factors involved in the pathogenesis of MS. There is no etiological therapy for MS and the drugs currently used, often accompanied by major side effects, are represented by immunomodulatory substances capable of modifying the course of the disease. For this reason, nowadays, more attention is paid to alternative therapies with natural substances with anti-inflammatory and antioxidant effects, as adjuvants of classical therapies. Among natural substances with beneficial effects on human health, polyphenols are assuming an increasing interest due to their powerful antioxidant, anti-inflammatory, and neuroprotective effects. Beneficial properties of polyphenols on the CNS are achieved through direct effects depending on their ability to cross the blood-brain barrier and indirect effects exerted in part via interaction with the microbiota. The aim of this review is to examine the literature about the molecular mechanism underlying the protective effects of polyphenols in MS achieved by experiments conducted in vitro and in animal models of the disease. Significant data have been accumulated for resveratrol, curcumin, luteolin, quercetin, and hydroxytyrosol, and therefore we will focus on the results obtained with these polyphenols. Clinical evidence for the use of polyphenols as adjuvant therapy in MS is restricted to a smaller number of substances, mainly curcumin and epigallocatechin gallate. In the last part of the review, a clinical trial studying the effects of these polyphenols in MS patients will also be revised.

Estimation of glomerular filtration rate from skeletal muscle mass. A new equation independent from age, weight, gender, and ethnicity.

BACKGROUND AND AIMS: The most used indicator for the renal function is the glomerular filtration rate (GFR). Current used predictive GFR equations were calibrated on patients with chronic kidney disease. Thus, they are not very precise in healthy individuals. The estimation of skeletal muscle mass (SMM) allows the prediction of the daily urinary creatinine excretion (24hUCrE). This study proposes an equation for the estimation of GFR based on SMM (eGFRMuscle) and serum creatinine (SCr). METHODS AND RESULTS: Four hundred sixty-six free-living men underwent a bioelectrical impedance analysis for the evaluation of SMM (kg), a blood withdrawal for the measurement of SCr (mg/dL), and a 24-h urinary collection for the assessment of 24hUCrE (g/24 h). The linear regression analysis between SMM and 24hUCrE and the measurement of SCr allowed developing a predictive equation of eGFRMuscle. The equation predicting eGFRMuscle (ml/min/1.73 m2) was SMM (kg) × 3.06/SCr (mg/dL). eGFRMuscle was statistically different from eGFR predicted by Cockroft-Gault, MDRD Study, and CKD-EPI equations (p = 0.017, p < 0.001, and p < 0.001, respectively). Pairwise comparison of standard error of the area under the ROC curve (AUC) of eGFRMuscle with all the other AUCs of ROC curves highlighted significant differences. CONCLUSIONS: The equation presented in this study results in age, weight, gender, and ethnicity independent because it arises directly from SMM estimation. Therefore, the proposed equation could allow evaluating the GFR also in healthy people with low, average, or high weight, and in older people, regardless of GFR and SCr levels.

Metabolism Regulation and Redox State: Insight into the Role of Superoxide Dismutase 1.

Energy metabolism and redox state are strictly linked; energy metabolism is a source of reactive oxygen species (ROS) that, in turn, regulate the flux of metabolic pathways. Moreover, to assure redox homeostasis, metabolic pathways and antioxidant systems are often coordinately regulated. Several findings show that superoxide dismutase 1 (SOD1) enzyme has effects that go beyond its superoxide dismutase activity and that its functions are not limited to the intracellular compartment. Indeed, SOD1 is secreted through unconventional secretory pathways, carries out paracrine functions and circulates in the blood bound to lipoproteins. Striking experimental evidence links SOD1 to the redox regulation of metabolism. Important clues are provided by the systemic effects on energy metabolism observed in mutant SOD1-mediated amyotrophic lateral sclerosis (ALS). The purpose of this review is to analyze in detail the involvement of SOD1 in redox regulation of metabolism, nutrient sensing, cholesterol metabolism and regulation of mitochondrial respiration. The scientific literature on the relationship between ALS, mutated SOD1 and metabolism will also be explored, in order to highlight the metabolic functions of SOD1 whose biological role still presents numerous unexplored aspects that deserve further investigation.

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.

Plasma p-cresol lowering effect of sevelamer in non-dialysis CKD patients: evidence from a randomized controlled trial.

BACKGROUND: The accumulation of p-cresol, a metabolic product of aromatic amino acids generated by intestinal microbiome, increases the cardiovascular risk in chronic kidney disease (CKD) patients. Therefore, therapeutic strategies to reduce plasma p-cresol levels are highly demanded. It has been reported that the phosphate binder sevelamer (SEV) sequesters p-cresol in vitro, while in vivo studies on dialysis patients showed controversial results. Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients. METHODS: This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKD patients (stage 3-5, not on dialysis), randomly assigned (1:1) to receive either SEV or placebo for 3 months. Total p-cresol serum levels were evaluated at baseline (T0), and 1 (T1) and 3 months (T3) after treatment start. The primary end-point was to evaluate the effect of SEV on p-cresol levels. RESULTS: Compared to baseline (T0, 7.4 ± 2.7 mg/mL), p-cresol mean concentration was significantly reduced in SEV patients after one (- 2.06 mg/mL, 95% CI - 2.62 to - 1.50 mg/mL; p < 0.001) and 3 months of treatment (- 3.97 mg/mL, 95% CI - 4.53 to - 3.41 mg/mL; p < 0.001); no change of plasma p-cresol concentration was recorded in placebo-treated patients. Moreover, P and LDL values were reduced after 3 months of treatment by SEV but not placebo. CONCLUSIONS: In conclusion, our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.

Comparison of the everolimus concentrations measured in whole blood with everolimus QMS or sirolimus CMIA.

Few years ago, it was proposed that everolimus blood levels could be determined with the commercially available sirolimus chemiluminescence magnetic microparticle immunoassay (CMIA). More recently, a highly specific microsphere system (QMS) has been approved by FDA for therapeutic drug monitoring in humans. Aim of the present study was to compare the results of everolimus assay performed with everolimus QMS and with sirolimus CMIA. The two methods were compared with Passing-Bablok regression and Bland-Altman plot analysis. The Passing-Bablok regression analysis showed that although the results obtained with the two techniques were significantly correlated, CMIA-measured differed from QMS-measured everolimus concentrations by both a systematic and a proportional error. Specifically, at blood levels lower than 5 ng/mL CMIA were lower than QMS-measured everolimus concentrations. On the opposite, at everolimus blood concentrations higher than 10 ng/mL CMIA-estimated values became progressively higher than QMS-measured everolimus concentrations. The analysis of the Bland Altman plot showed a less than optimal agreement of the two tests (5.59% of the data point outside the ±1.96 SD interval). Moreover, the relationship between the difference between EveroQMS and EveroCMIA and their average was clearly concentration dependent with positive and negative values at concentration values lower and higher than 5 ng/mL respectively. In conclusion, our finding showed that the values of everolimus concentrations measured with sirolimus CMIA differ from those detected with the FDA-approved everolimus QMS further suggesting that sirolimus CMIA should not be used anymore for everolimus therapeutic drug monitoring.

Validation of daily urinary creatinine excretion measurement by muscle-creatinine equivalence.

BACKGROUND: Twenty-four-hour urinary creatinine excretion (24hUCrE) is strongly correlated with skeletal muscle mass (SMM). This study suggests how to exploit the power of the SMM-24hUCrE correlation to assess the accuracy of 24hUCrE measurement. METHODS: Four hundred and sixty-six men, a subgroup of participants in the 2002-2004 follow-up examination of the Olivetti Heart Study, performed a 24-h urine collection to measure 24hUCrE and underwent bioelectrical impedance analysis to evaluate SMM. Linear regression analysis between 24hUCrE and SMM was used to calculate the muscle-creatinine equivalence and to develop an equation to predict the 24hUCrE depending on SMM. The accuracy of the 24hUCrE measurement was assessed using the change in the SMM-24hUCrE correlation coefficient upon variation in the percentage deviation (%D) between the measured and predicted 24hUCrE. RESULTS: The calculated muscle-creatinine equivalence was 1 g of 24hUCrE = 22.73 kg of SMM. The %Ds and the corresponding SMM-24hUCrE correlation coefficients were as follows: %D = 3.0, r = .997; %D = 4.7, r = .989; %D = 8.1, r = .963; %D = 10.5, r = .940; %D = 12.6, r = .909; %D = 18.9, r = .825; %D = 25.8, r = .707; %D = 33.5, r = .595; %D = 41.4, r = .453. CONCLUSION: The increase in %D corresponds to a reduced correlation between muscle mass and creatinine excretion, which indicated a poor performance in the measurement of the 24hUCrE. For studies on single individuals, where small variations in 24hUCrE could be significant, a %D up to 12.6% is suggested; on the other hand, a wider %D interval could be acceptable for population studies.

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.

Children of a lesser god or miracles? An emotional and behavioural profile of children born to mothers on dialysis in Italy: a multicentre nationwide study 2000-12.

BACKGROUND: Pregnancy on dialysis is increasingly being reported. This study evaluates the behavioural profile of the children of mothers on dialysis and the parental stress their mothers undergo when compared with a group of mothers affected by a different chronic disease (microcythaemia) and a group of healthy control mothers. METHODS: Between 2000 and 2012, 23 on-dialysis mothers gave birth to 24 live-born children in Italy (23 pregnancies, 1 twin pregnancy, one of the twins deceased soon after delivery); of these, 16 mothers and 1 father (whose wife died before the inquiry) were included in the study (1 mother had died and the father was unavailable; 2 were not asked to participate because their children had died and 3 were unavailable; children: median age: 8.5, min-max: 2-13 years). Twenty-three mothers affected by transfusion-dependent microcythaemia or drepanocitosis (31 pregnancies, 32 children) and 35 healthy mothers (35 pregnancies, 35 children; median age of the children: 7, min-max: 1-13 years) were recruited as controls. All filled in the validated questionnaires: 'Child Behaviour Checklist' (CBCL) and the 'Parental Stress Index-Short Form' (PSI-SF). RESULTS: The results of the CBCL questionnaire were similar for mothers on dialysis and healthy controls except for pervasive developmental problems, which were significantly higher in the dialysis group, while microcythaemia mothers reported higher emotional and behavioural problems in their children in 8 CBCL sub-scales. Two/16 children in the dialysis and 3/32 in the microcythaemia group had pathological profiles, as assessed by T-scores (p: ns). PSI-SF indicated a normal degree of parental stress in microcythaemia subjects and healthy controls, while mothers on dialysis declared significantly lower stress, suggesting a defensive response in order to minimize problems, stress or negativity in their relationship with their child. CONCLUSIONS: According to the present analysis, the emotional and behavioural outcome is normal in most of the children from on-dialysis mothers. A 'positive defence' in the dialysis mothers should be kept in mind when tailoring psychological support for this medical miracle.

Evidence That Skeletal Muscles Modulate HDL-Cholesterol in Metabolic Healthy Young Adults.

The aim of this study was to investigate whether skeletal muscle (SM) mass correlates with plasma lipids in metabolic healthy young adults. The study was designed as a retrospective observational monocentric study. Data on plasma lipids and SM mass of subjects attending our institution from 1999 to 2014 were analyzed. Inclusion criteria were being 18-45 years old and in apparently good health. SM mass was evaluated by bioelectrical impedance analysis (BIA) using the equation proposed by Janssen and normalized to height as skeletal muscle index (SMI: SM mass/height2). The association between SMI and plasma lipids levels was examined using a crude and adjusted linear regression model including age, sex, BMI and waist circumference as additional covariates. The study population consisted of 450 subjects (273 females) without metabolic syndrome (12.2% with normal body weight, 33.1% overweight, and 54.7% with obesity). SMI, total-cholesterol, LDL-cholesterol, and Triglycerides were higher, whereas HDL-cholesterol was lower in overweight and obese patients as compared with normal weight subjects. SMI was inversely associated with HDL-cholesterol in female patients with obesity but not in male patients with obesity, in normal- or over-weight subjects (p < 0.05). These results suggest that changes in SM mass occurring in obesity could have a role in worsening lipid profile with special reference to HDL-cholesterol.

Effects of Dietary Intervention on Nutritional Status in Elderly Individuals with Chronic Kidney Disease.

The prevalence of chronic kidney disease (CKD) is rising, especially in elderly individuals. The overlap between CKD and aging is associated with body composition modification, metabolic abnormalities, and malnutrition. Renal care guidelines suggest treating CKD patient with a low-protein diet according to the renal disease stage. On the other hand, geriatric care guidelines underline the need for a higher protein intake to prevent malnutrition. The challenge remains of how to reconcile a low dietary protein intake with insuring a favorable nutritional status in geriatric CKD populations. Therefore, this study aims to evaluate the effect of a low-protein adequate energy intake (LPAE) diet on nutritional risk and nutritional status among elderly CKD (stage 3-5) patients and then to assess its impact on CKD metabolic abnormalities. To this purpose, 42 subjects [age ≥ 65, CKD stage 3-5 in conservative therapy, and Geriatric Nutritional Risk Index (GNRI) ≥ 98] were recruited and the LPAE diet was prescribed. At baseline and after 6 months of the LPAE diet, the following data were collected: age, sex, biochemical parameters, anthropometric measurements, body composition, and the GNRI. According to their dietary compliance, the subjects were divided into groups: compliant and non-compliant. For the compliant group, the results obtained show no increased malnutrition risk incidence but, rather, an improvement in body composition and metabolic parameters, suggesting that the LPAE diet can provide a safe tool in geriatric CKD patients.

Hypothalamic-Ovarian axis and Adiposity Relationship in Polycystic Ovary Syndrome: Physiopathology and Therapeutic Options for the Management of Metabolic and Inflammatory Aspects.

PURPOSE OF REVIEW: The goal of the present review is to address the main adiposity-related alterations in Polycystic Ovary Syndrome (PCOS) focusing on hypothalamic-pituitary-ovarian (H-P-O) axis and to provide an overview of nutraceutical and pharmacological therapeutic strategies. RECENT FINDINGS: Female reproduction is a complex and delicate interplay between neuroendocrine signals involving the H-P-O axis. Elements that disrupt the balance of these interactions can lead to metabolic and reproductive disorders, such as PCOS. This disorder includes menstrual, metabolic, and biochemical abnormalities as well as hyperandrogenism, oligo-anovulatory menstrual cycles, insulin resistance, and hyperleptinemia which share an inflammatory state with other chronic diseases. Moreover, as in a self-feeding cycle, high androgen levels in PCOS lead to visceral fat deposition, resulting in insulin resistance and hyperinsulinemia, further stimulating ovarian and adrenal androgen production. In fact, regardless of age and BMI, women with PCOS have more adipose tissue and less lean mass than healthy women. Excessive adiposity, especially visceral adiposity, is capable of affecting female reproduction through direct mechanisms compromising the luteal phase, and indirect mechanisms as metabolic alterations able to affect the function of the H-P-O axis. The intricate crosstalk between adiposity, inflammatory status and H-P-O axis function contributes to the main adiposity-related alterations in PCOS, and alongside currently available hormonal treatments, nutraceutical and pharmacological therapeutic strategies can be exploited to treat these alterations, in order to enable a more comprehensive synergistic and tailored treatment.

Effects of a diet rich in N-3 polyunsaturated fatty acids on systemic inflammation in renal transplant recipients.

OBJECTIVE: n-3 Polyunsaturated fatty acids (PUFAs) supplementation reduces systemic inflammation and improves renal and cardiovascular prognosis in kidney transplant recipients. However, patient compliance is poor because bad-tasting fish oils are used as an n-3 PUFA source. Therefore, we explored whether the beneficial effects of n-3 can be obtained by administering a diet based on n-3-rich foods. METHODS: Sixty kidney transplant recipients were assigned to 2 different groups: the CON group (n = 28), which continued with their usual diet, and the DIET group (n = 32), which followed an n-3-rich diet for 6 months. Twenty-six patients in the DIET group and 24 in the CON group completed the study. End points of the study were changes in n-3 PUFAs intake, n-6:n-3 PUFAs ratio, systemic inflammation markers, and renal function during the 6 months of the dietary treatment. RESULTS: Three and 6 months after the beginning of the study, n-3 PUFA intake was significantly higher and the n-6:n-3 PUFA ratio was markedly lower than baseline in the DIET group. Plasma total cholesterol, triglycerides, C-reactive protein, and interleukin (IL)-6 decreased as well. IL-6 mRNA levels in peripheral blood mononuclear cells were also lower than at the beginning of the study. Proteinuria and microalbuminuria were reduced by 50% with respect to the baseline, whereas glomerular filtration rate (GFR) was unchanged. No change in the aforementioned parameters was observed in the CON group throughout the study. CONCLUSION: In long-term kidney transplant recipients a naturally n-3 PUFA-rich dietary plan causes an increase in n-3 PUFA intake, decreases systemic inflammation and proteinuria, and improves plasma lipid pattern.

Evidence on the prevalence and geographic distribution of major cardiovascular risk factors in Italy.

OBJECTIVE: To assess the prevalence and geographic distribution of major cardiovascular risk factors in a large community-wide sample of the Italian population. DESIGN: A cross-sectional survey. Standardized methods were used to collect and measure cardiovascular risk factors. Data were adjusted for survey weightings. Qualitative and quantitative variables were compared with parametric and non-parametric tests, as appropriate. SETTING: Towns (n 193) across different Italian regions. SUBJECTS: Unselected adults (n 24 213; 12 626 men; 11 587 women) aged 18-98 years (mean age 56·9 (sd 15·3) years), who volunteered to participate in a community-wide screening programme over a 2 d period in 2007. RESULTS: Overall, the prevalence of major cardiovascular risk factors was: obesity, 22·7 % (women 18·9 %, men 26·1 %); overweight, 44·7 % (women 31·6 %, men 56·7 %); hypertension, 59·6 % (women 48·3 %, men 70·0 %); dyslipidaemia, 59·1 % (women 57·7 %, men 60·3 %); diabetes, 15·3 % (women 11·2 %, men 19·0 %) and smoking, 19·8 % (women 14·0 %, men 25·2 %). We found a high prevalence of unhealthy eating habits; fruit and vegetable consumption was below the recommended range in 60 % of the study population. Ninety per cent of the study population had more than one cardiovascular risk factor and 84 % had between two and five cardiovascular risk factors. There were differences among Italian macro-areas mainly for obesity, hypertension, dyslipidaemia and diabetes. CONCLUSIONS: The study provides alarming evidence on current prevalence data for major cardiovascular risk factors in a large sample of the Italian population. Particularly, obesity and hypertension represent a relevant public health problem. There is a pressing need for effective preventive health measures which must also take into account the differences among Italian macro-areas.

The Effects of a Cinchona Supplementation on Satiety, Weight Loss and Body Composition in a Population of Overweight/Obese Adults: A Controlled Randomized Study.

Obesity is a risk factor for several diseases present worldwide. Currently, dietary changes and physical activity are considered the most effective treatment to reduce obesity and its associated comorbidities. To promote weight loss, hypocaloric diets can be supported by nutraceuticals. The aim of this study was to evaluate the effects of a hypocaloric diet associated with Cinchona succirubra supplementation on satiety, body weight and body composition in obese subjects. Fifty-nine overweight/obese adults, were recruited, randomized into two groups and treated for 2 months. The first group (32 adults) was treated with a hypocaloric diet plus cinchona supplementation (the T-group); the second one (27 adults) was treated with a hypocaloric diet plus a placebo supplementation (the P-group). Anthropometric-measurements as well as bioimpedance analysis, a Zung test and biochemical parameters were evaluated at baseline and after 60 days. T-group adults showed significant improvement in nutritional status and body composition compared to those at the baseline and in the P-group. Moreover, T-group adults did not show a reduction in Cholecystokinin serum levels compared to those of P-group adults. In conclusion, our data demonstrate that a hypocaloric diet associated with cinchona supplementation is effective in inducing more significant weight loss and the re-establishment of metabolic parameters than those obtained with a hypocaloric diet.

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review.

The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.

Human mature adipocytes express albumin and this expression is not regulated by inflammation.

AIMS: Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. METHODS: Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. RESULTS: A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. CONCLUSIONS: In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin.