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The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.

A 30-year-old woman with severe hypertension was admitted to the hospital with a history of headache, palpitations, and diaphoresis following sexual intercourse. Twenty-four hour urinary excretion of free catecholamines and metabolites was markedly increased as was serum chromogranin A. Computed tomography scan revealed a large mass in the left adnex site and magnetic resonance imaging confirmed the computer tomography finding, suggesting the presence of extra-adrenal sympathetic paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake in the same area. Transcatheter arterial embolization of the mass resulted in marked decreases in blood pressure and urinary excretion of free catecholamines and metabolites. Surgical excision of the mass was then accomplished without complication. Preoperative embolization is a useful and safe procedure which may reduce the risk of catecholamines release at the time of surgical excision in large pelvic extra-adrenal sympathetic paraganglioma.

Electrolyte disorders may constitute a life-threatening emergency. Sometimes they can be treated with medical therapy but there are cases where emergency dialysis will be necessary. An important role is played by the dialysate (including different concentrations of electrolytes), which removes uremic toxins and balances the electrolyte disorders in patients with end-stage renal disease. The choice of dialysate is also important for control of the patient's vital functions during the dialysis session and in the period between sessions. Sodium is strongly related to weight gain between dialysis sessions and its concentration causes fluid overload or, on the contrary, hypotension. The choice of the buffer takes into account any possible bicarbonate- or acetate-related systemic effects. Potassium is very important for heart contraction and its fast removal could be associated with cardiac arrhythmias. The role of magnesium is still controversial. Calcium is related to hemodynamic stability, mineral bone disease and also cardiac arrhythmias. A correctly balanced dialysate is important to prevent and reduce intradialytic and interdialytic complications. The dialysate should be tailored to the needs of the individual patient.

The treatment of pain in patients with impaired renal function may be problematic, especially when opioid drugs need to be used. In the presence of renal failure, significant changes occur in the metabolism and pharmacokinetics of these drugs, which can lead to adverse reactions due to the accumulation of parental compounds and active metabolites. This paper presents and discusses the available evidence concerning the optimal use of the most frequently employed opioid analgesics to treat pain in patients with renal impairment.

T regulatory cells are fundamental in the maintenance of immune homeostasis and self-tolerance. Experimental models suggest the existence of two functional types of T(reg) cells designated naturally occurring and induced. Interest in T(reg) cells increased with evidence from experimental mouse and human models demonstrating that the immunosuppressive potential of these cells can be utilized in the treatment of various pathological conditions. The existence of a subpopulation of suppressive T cells was the subject of significant controversy among immunologists for many years. T regulatory cells limit immune activation through a variety of direct and indirect interactions, many of which are yet to be determined. Fully understanding T(reg) cells biology will lead us to harnessing the capacity of these cells in order to develop strategies to prevent autoimmune disorders and tolerance to transplantation. Efficient isolation, expansion and cryopreservation strategies that comply with Good Manufacturing Practice (GMP) guidelines are prerequisites for the clinical application of human CD4+ CD25+ CD127(low) FOXP3+ regulatory T cells.

Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

High-dose chemotherapy followed by reinfusion of autologous stem cells harvested from peripheral blood has been increasingly applied for a variety of disorders. The critical importance of cell dose in the clinical outcome, after transplant, has motivated the need to develop techniques aimed at reducing cell losses and increasing reproducibility.The aim of this study is to evaluate the efficacy of the Sepax S-100 device to process thawed HPC-A products in comparison with manual procedure.We have analysed viability, total nucleated cells (TNC), haematopoietic progenitors and CD34+ cells recovery.The TNC and CD34+ cells recovery in the automatic procedure was of 91.9% (73-100; SD ± 12.60) and 86.7% (69-100; SD ± 10.21), respectively. Instead the recovery of TNC and CD34+ cells using the manual method was of 84.7% (47-100; SD ± 22.9) and 80.29% (23-100; SD ± 25.96). The results, obtained from the assessment of viability of CD34+ both 7-AAD)+ and AnnV+ showed a high percentage of necrosis and apoptosis in this cell subset by using the manual procedure in respect to the Sepax automated system.Overall, our data suggest that the automated washing procedure is safe and suitable for processing of thawed HPC-A products and can be daily used in clinical routine.

Objectives: Total body potassium (TBK) is an index of fat-free mass and an accurate measure of body cell mass (BCM). To date, however, no longitudinal studies have evaluated body composition using TBK in aging healthy adults. The purpose of this study was to assess TBK and BCM in healthy men over a 21-year period, and to evaluate changes with age. Design: A 21-year longitudinal, prospective, observational study evaluating TBK and BCM and their relationship to changes with aging and body mass index (BMI). Subjects: Body composition of 133 healthy Italian men, 20 to 66 years of age, was measured by whole-body counting of 40 K. TBK was calculated by using this formula: 40 K 3 8.474. BCM was calculated from TBK by using this formula: BCM (kg) 5 0.00833 3 TBK (mmol). Results: The prevalence of overweight and obesity increased significantly from baseline to end of study (p , 0.01), with no change in TBK observed over the 21-year period. BCM summaries were tested to determine if any was a good predictor of BMI after age 30. Participants with a low maximum BCM (,27 kg) at an early age tended to exhibit decreased BMI as they aged, whereas those with a high maximum BCM (.27 kg) at an early age tended to show increased BMI as they aged. Conclusion: Despite an overall increase in the incidence of overweight and obesity over the 21-year period, a high maximum BCM at an early age was a predictor of an increase in BMI as men got older.

Obesity is associated with endothelial dysfunction related to decreased NO bioavailability, increased endothelin 1 vasoconstrictor activity, and decreased circulating ghrelin. Therefore, we tested whether exogenous ghrelin may have benefits to improve the balance between endothelin 1 and NO in patients with obesity-related metabolic syndrome. Vasoactive actions of endothelin 1 and NO were assessed in 8 patients with metabolic syndrome and 8 matched controls by evaluating forearm blood flow responses (strain-gauge plethysmography) to intra-arterial infusion of BQ-123 (endothelin A receptor antagonist; 10 nmol/min), followed by N G -monomethyl- l -arginine (NO synthase inhibitor; 4 μmol/min), before and after infusion of ghrelin (200 ng/min). In the absence of ghrelin, the vasodilator response to BQ-123 was greater in patients than in controls ( P N G -monomethyl- l -arginine induced smaller vasoconstriction in patients than in controls ( P =0.006). Importantly, exogenous ghrelin decreased the vasodilator response to BQ-123 ( P =0.007 versus saline) and enhanced the magnitude of changes in forearm blood flow induced by N G -monomethyl- l -arginine ( P =0.003) in patients but not in controls (both P >0.05). The favorable effect of ghrelin on endothelin A–dependent vasoconstriction was likely related to the stimulation of NO production, because no change in the vascular effect of BQ-123 was observed after ghrelin ( P =0.44) in 5 patients with metabolic syndrome during continuous infusion of the NO donor sodium nitroprusside (0.2 μg/min). In patients with metabolic syndrome, ghrelin has benefits to normalize the balance between vasoconstrictor (endothelin 1) and vasodilating (NO) mediators, thus suggesting that this peptide has important peripheral actions to preserve vascular homeostasis in humans.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values1 (normal status PINI1). After the pharmacological treatment, high significant (P0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

Diabetes Res Clin Pract. 2007 Nov;78(2):298-9. Epub 2007 May 3. Insulin glargine in enteric tube feeding. Marchetti G, Tesauro M, Di Daniele N, Bollea MR, Lauro R, Bertoli A. Insulin glargine, a long-acting insulin analogue, was introduced to provide effective basal insulin replacement with once-daily dosing. An insulin regimen with insulin glargine allows optimal glucose control with a lower risk of hypoglycaemia compared with neutral protaminated hagedorn insulin in Type 2 diabetes [1,2]. Recently, insulin glargine has been proposed for patients on continuous enteral artificial nutrition [3,4]. We report an 18-month follow-up of a patient treated with basal insulin glargine during continuous enteral nutrition and thereafter during intermittent enteral nutrition without evidence of hypoglycaemic events.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians, with a frequency of ∼ 1 in 3000 live births. The mutated gene is a defective chloride channel in epithelial cells, named cystic fibrosis transmembrane conductance regulator (CFTR). Several different protocols for the scanning of the entire gene have aided molecular diagnosis and improved our understanding of the disorder’s pathophysiology, but also showed the disease’s complexity. Therefore, CF phenotype remains difficult to predict from CFTR mutation data alone: several studies have suggested that additional genes could modulate its clinical outcome. Gene replacement therapy is still far from being used in patients with CF, mostly due to the difficulties with targeting the appropriate cells. In this review, we summarize recent advances, both in the pharmacological and gene therapy field, aimed for the treatment of the disease.

To investigate whether skeletal muscle uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) gene expression is altered in massive obesity and whether it correlates with in vivo insulin sensitivity and with metabolic and hormonal status.Quantification of UCP2 and UCP3 gene expression in skeletal muscle of obese and lean subjects displaying different degrees of insulin sensitivity.Fourteen obese and 10 age- and sex-matched healthy control subjects with a mean body mass index (BMI) of 43.6 +/- 1.4 and 22.8 +/- 1.8 (+/- SEM), respectively.Insulin sensitivity by glucose clamp, body composition by bio-impedance, fasting plasma glucose, insulin, leptin and free fatty acids (FFA). Skeletal muscle UCP2 and UCP3 mRNA levels by quantitative reverse transcription polymerase chain reaction (RT-PCR).No significant differences in UCP2 or UCP3 mRNA levels were found between obese and control subjects. No significant correlation was observed, in both groups, between UCP2 or UCP3 mRNA levels and both anthropometrical and metabolic parameters. In contrast, a highly significant correlation was observed between skeletal muscle UCP3, but not UCP2, mRNA levels and plasma FFA in the obese, but not in the lean, group. Furthermore, exposure of human myocytes to FFA for 24 h strongly induced both UCP3 and peroxisome proliferator-activated receptor-gamma (PPARgamma) but not UCP2 gene expression.FFA levels correlate strongly with skeletal muscle UCP3 mRNA levels in obese, but not in lean, subjects; in addition, in human myocytes, high FFA concentrations promote UCP3 expression. Our studies therefore provide evidence that supports a role for increased plasma FFA concentrations in the regulation of human skeletal muscle UCP3 gene expression.

Obesity symbolizes a major public health problem. Overweight and obesity are associated to the occurrence of the metabolic syndrome and to adipose tissue dysfunction. The adipose tissue is metabolically active and an endocrine organ, whose dysregulation causes a low-grade inflammatory state and ectopic fat depositions. The Mediterranean Diet represents a possible therapy for metabolic syndrome, preventing adiposopathy or “sick fat” formation. The Mediterranean Diet exerts protective effects in elderly subjects with and without baseline of chronic diseases. Recent studies have demonstrated a relationship between cancer and obesity. In the US, diet represents amount 30-35% of death causes related to cancer. Currently, the cancer is the second cause of death after cardiovascular diseases worldwide. Furthermore, populations living in the Mediterranean area have a decreased incidence of cancer compared with populations living in Northern Europe or the US, likely due to healthier dietary habits. The bioactive food components have a potential preventive action on cancer. The aims of this review are to evaluate the impact of Mediterranean Diet on onset, progression and regression of metabolic syndrome, cancer and on longevity.