Annalisa Noce

Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.

Renal Resistive Index and Long-term Outcome in Chronic Nephropathies

PURPOSE To assess the clinical validity of renal resistive index (RI) to determine prognosis and guide therapy over a long-term follow-up in patients with chronic nephropathies and to verify the commonly used threshold value of 0.70. MATERIALS AND METHODS Of patients referred to the nephrology center since 1995, 177 were initially enrolled and 86 were followed up for RI and renal function annually for 2-11 years (mean, 5.93 years +/- 2.92 [standard deviation]). All patients gave informed consent for the institutional review board-approved study. Correlations were determined between initial RI and age, estimated glomerular filtration rate (eGFR), proteinuria, hematuria, blood pressure, and biopsy scores. The sample was categorized in four groups on the basis of whether initial values of RI and eGFR were normal, and progression to renal failure was compared. With grouping of the sample by using initial RI (< or =0.61, 0.62-0.69, and > or =0.70), Kaplan-Meier analysis was used to obtain survival curves. RESULTS Initial RI correlated with final eGFR (R = -0.4, P < .001), systolic blood pressure (R = 0.39, P < .001), proteinuria (R = 0.28, P = .009), and age (R = 0.28, P = .007). In stepwise multiple regression analysis, RI emerged as the only independent risk factor for the progression to renal failure (P < .001). Among the four groups of patients with different initial RIs and eGFRs, the group with an initial RI of 0.70 or higher showed a worse outcome, independent of initial eGFR. In the Kaplan-Meier analysis by using initial RI, only the group with a value of 0.70 or higher showed a rapid decline of renal function (>50% decrease in eGFR in 6 years). CONCLUSION An RI of 0.70 or higher is predictive of an unfavorable outcome in patients with chronic nephropathies.

Atherosclerosis, dyslipidemia, and inflammation: the significant role of polyunsaturated Fatty acids.

Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed “eicosanoids,” which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have anti-inflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolism.

Prospective assessment of body weight and body composition changes in patients with psoriasis receiving anti-TNF-α treatment

Tumor necrosis factor (TNF)‐α is a pro‐inflammatory cytokine associated with psoriasis pathogenesis. Anti‐TNF‐α therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti‐TNF‐α agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti‐TNF‐α therapies according with disease phenotype. Forty patients affected with psoriasis were followed up for 24 weeks and divided into two groups: psoriasis vulgaris (PsO) and psoriatic arthritis (PsA). Anthropometric, blood biochemical, body composition parameters, resting metabolic rate, and disease activity indexes were measured at baseline and at week 24. After 24 weeks of anti‐TNF‐α administration, the disease activity indexes and concentration of inflammatory markers were significantly decreased. Seventy‐five percent of PsO and 60% of PsA patients had an increase in body weight. Weight changes correlated with fat mass gain in the PsO group, and with fat and lean mass gain in the PsA group. In the present study, we demonstrated that a blockage of TNF‐α bioactivity is related with fat and lean mass gain in both PsO and PsA subjects. The anti‐TNF‐α therapies could play a key role in the cross talk between adipose tissue and skeletal muscle, mediated by the reduction of TNF‐α and interleukin‐6 production.

Impact of Mediterranean diet on metabolic syndrome, cancer and longevity

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.

Chronic treatment with statins increases the availability of selenium in the antioxidant defence systems of hemodialysis patients.

PROJECT Oxidative stress (OS) is enhanced in hemodialysis (HD) patients. Lipid peroxidation and oxidative damage to glycids, proteins and nucleic acids are the main consequences of OS and are associated with increased cardiovascular risk. Vitamin E and glutathione peroxidase (GSH-Px) represent the main antioxidant systems in human cells. Selenium (Se), bound to the active sites of GSH-Pxs, plays a critical role in this antioxidant defence system. Statins are widely used and extensively investigated in the prevention of cardiovascular disease, notably in high-risk subjects. Several studies show antioxidant effects of statins not related to their lipid-lowering action. Our study aimed to compare serum Se concentration in ESRD patients on maintenance HD and in homogeneous healthy subjects and to investigate whether chronic treatment with statins may interfere with serum Se concentration in HD patients. PROCEDURE A total of 103 HD patients and 69 healthy subjects were enrolled; HD patients were divided into patients who were not treated with statins (group A) and patients who assumed statins since 6 months at least (group B). Serum Se was determined by atomic absorption spectrometry. RESULTS Serum Se was significantly lower in HD patients of group A compared with healthy subjects (81.65+/-19.66 Vs. 96.47+/-15.62 mcg/L, p<0.0040). However, in HD patients who assumed statins serum, Se was significantly higher than in HD patients who did not (111.83+/-18.82 vs. 81.65+/-19.66 mcg/L, p<0.0001). CONCLUSIONS Our results suggest that in HD patients chronic treatment with statins is related to higher-serum Se concentration.

The usefulness of the prognostic inflammatory and nutritional index (PINI) in a haemodialysis population.

BACKGROUND AND AIM Protein-Energy Wasting and inflammation are the principal risk factors of haemodialysis complications. We evaluated the reliability of a simple and non expensive test, the Prognostic Inflammatory and Nutritional Index (PINI), for regular screening of maintenance haemodialysis (MHD) patients in order to detect early onset of inflammation and malnutrition. METHODS AND RESULTS 121 adult patients on maintenance dialysis were followed up for 32 months and screened every 6 months for PINI, calculated as alpha1-Acid Glycoprotein (alpha1-AG)xC-Reactive Protein (CRP)/AlbuminxTransthyretin. PINI score < or =1 was considered normal. Patients were stratified according to their PINI score: 86 patients (71.66%) had a normal score, whereas 35 (28.33%) had PINI > or = 1. The latter also had higher CRP levels, despite no clinical evidence of inflammation at the time of enrolment. Survival in patients with normal PINI was similar to patients with normal CRP, while in patients with abnormal PINI it was significantly lower than in patients with low serum albumin (p<0.05) or elevated CRP (p<0.05). After follow-up, all surviving MHD patients with PINI > or = 1 had at least one cardiovascular event vs 2.5% of patients with PINI > or = 1. CONCLUSION The assessment of PINI can reliably identify MHD patients at higher risk of mortality and morbidity even in the absence of overt Malnutrition-Inflammation Complex Syndrome (MICS). This simple test appears to be more sensitive and specific of the single components, and not expensive, so that it could be routinely used to identify patients with sub-clinical inflammation and/or malnutrition.

Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome

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 values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) 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 PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

The possible role of glutathione-S-transferase activity in diabetic nephropathy

The most common cause of end stage renal disease is diabetic nephropathy. An early diagnosis may allow an intervention to slow down disease progression. Recently, it has been hypothesized that glutathione-S-transferase (GST) activity may be a marker of severity of chronic kidney disease. In particular, a lower GST activity is present in healthy subjects compared to patients with nephropathy. In the present review we illustrate the scientific evidence underlying the possible role of GST activity in the development of diabetic nephropathy and we analyze its usefulness as a possible early biomarker of this diabetic complication.

Erythrocyte glutathione transferase in uremic diabetic patients: additional data

We found that erythrocyte glutathione transferase, an enzyme devoted to the body detoxification from endogenous and exogenous toxins, is overexpressed in humans in case of increased blood toxicity as it occurs in kidney dysfunctions and environmental pollution [1–3]. In a recent paper, we also reported that erythrocyte glutathione transferase (e-GST) may be an early biomarker for kidney dysfunction in diabetic patients [4]. More precisely, we found that a statistically significant increase in e-GST activity is present in diabetic patients even in the absence of an increase in traditional biomarkers of kidney damage i.e., albuminuria [4]. Evidence was also given that the observed increase is not caused by diabetes per se. The hypothesis that e-GST may indicate an incipient defect in the kidney functionality is a fascinating idea that must be corroborated by further investigations and epidemiologic studies. In this context, we explored the possibility that e-GST hyperexpression could correlate with some of the many biomarkers usually tested in diabetic diseases. In Table 1 are summarized the possible correlation of some clinical parameters between the different groups (healthy subjects, diabetic non-nephropatic patients, and diabetic nephropatic patients). Table 2 shows that no evident correlation is present among e-GST and some clinical parameters. The absence of correlation confirms that e-GST must be considered a novel biomarker which reveals an incipient kidney defective function in case of diabetic disease. The early increase in the e-GST activity in diabetic patients without any apparent signal of renal damage can be explained by assuming an elevation of the circulating toxins and not as a consequence the modification of other classical parameters. Recently, e-GST, present in the erythrocytes and easily measured, has disclosed new possible use as biomarker of kidney status in transplanted patients that will be object of future investigations.