The absence of polymorphisms in ADRB3, UCP1, PPARγ, and ADIPOQ genes protects morbid obese patients toward insulin resistance.

BACKGROUND AND AIMS: The insulin resistance (IR) is a major metabolic impairment in severe obesity, a multifactorial disease in which the importance of the effect of single nucleotide polymorphisms (SNP) associations in different rather than individual genes was established. The aim of this study was to test the predictive value of presence/absence of polymorphisms/ variants in ß3-adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ), and adiponectin (ADIPOQ) genes in diagnosing the IR in obesity. SUBJECTS AND METHODS: We studied 112 (40 males, 72 females) severely obese (body mass index: 48.5±7.5 kg/m2) subjects recruited from the outpatient obesity clinic of Federico II University Hospital in Naples. Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARγ, and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay or by direct sequencing (ADIPOQ). RESULTS AND CONCLUSION: Our results demonstrate that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further, the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or Pro12Ala in PPARγ and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a useful prognostic factor (NPV=100%) toward the IR onset in these obese patients representing a further parameter for an earlier and appropriate therapy.

UCP1 -3826 AG+GG genotypes, adiponectin, and leptin/adiponectin ratio in severe obesity.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.

Standard Carotid Endarterectomy versus Carotid Artery Stenting with Closed-Cell Stent Design and Distal Embolic Protection: does the age matter?

Carotid artery endarterectomy (CEA) is considered the gold standard for treatment of symptomatic and asymptomatic carotid disease. Carotid artery stenting (CAS) is a less invasive approach and therefore could be considered a viable alternative to CEA, especially in high-risk patients or those with relative contraindications to CEA (i.e. actinic stenosis, post-CEA restenosis, previous neck or tracheostomy surgery, contralateral laryngeal nerve paralysis, etc.). METHODS: The aim of this study is to evaluate the short- and medium-term outcomes of CAS performed with a single type of closed-cell stent design and distal filter protection by comparing the procedure with CEA based upon 3 endpoints: overall survival rate, stroke free survival rate and restenosis free survival rate.The same endpoints were also evaluated in 2 different age groups, more and less than 70 years, to show possible age-based differences on outcomes.Among 105 patients (77 males, 28 females), 74 were submitted to CEA and 31 were subject to CAS.In all cases the same self-expanding stent with closed-cell design (XACT Carotid Stent, Abbott Vascular) and the same distal embolic protection device (Emboshield NAV, Abbott Vascular) were employed. RESULTS: At 12 months, no statistically significant difference was observed in overall survival rates (CEA 93.2% vs CAS 93.5%, p=0.967) and restenosis free survival rates (CEA 94.5% vs CAS 96.8%, p=0.662).An increased stroke free survival rate was observed in the CEA group when compared to the CAS group (CEA 100.0% vs CAS 93.5%, p=0.028).The age-based endpoints didn't show any significant difference. CONCLUSION: These results suggest that CEA still remains the gold standard of treatment for carotid stenosis given its greater efficacy in the prevention of stroke CAS. However, CAS could be considered as an alternative treatment to CEA to be used in select cases only.

Molecular analysis of the adiponectin gene in severely obese patients from southern Italy.

BACKGROUND: Severe obesity is a major worldwide public health concern affecting 0.5-5% of the adult population. Adiponectin (Acpr30), an adipokine secreted from adipocytes, shows pleiotropic beneficial effects on obesity and related disorders. In this study, sequence analysis of Acpr30 gene (ACDC) was performed in a highly selected population of severely obese young adult patients from Southern Italy to investigate the associations between polymorphisms in the ACDC gene and the development of severe obesity concomitantly with other features of the metabolic syndrome. METHODS: The ACDC gene was analyzed by direct sequencing in the severely obese patients (n=220) and compared to healthy controls (n=116). The associations between the ACDC gene single-nucleotide polymorphisms (SNPs) and the levels of serum Acpr30 as well as the correlation with the presence of severe obesity jointly associated with other features of the metabolic syndrome were also investigated. Total serum Acpr30 concentrations were measured by the ELISA method. RESULTS: ACDC gene molecular screening revealed the presence of previously described SNPs and a new nucleotide alteration, c.355T>G, leading to a protein variant, p.L119V. Measurement of serum concentration of Acpr30 demonstrated lower levels of Acpr30 in the obese population compared to controls (30.5+/-28.3 vs. 43.9+/-35.7 microg/ml, p<0.01); in particular, significantly lower Acpr30 concentrations were observed in obese patients bearing c.-11377C>G SNP CG+GG genotypes than in those with CC genotype (22.9+/-20.5 vs. 33.1+/-29.4 microg/ml, p<0.05). CONCLUSIONS: Our results confirmed that low serum levels of Acpr30 are related to severe obesity and a difference in protein expression is associated with variants in ACDC gene promoter region.

Treatment of de novo femoro-popliteal lesions with a new Drug Coated Balloon: early experience of a single Center in the first 50 patients.

Angioplasty with drug-coated balloon (DCB) is an emerging and reliable method for the treatment of femoro-popliteal lesions. We report our experience with the Stellarex™ DCB in the first 50 patients. METHODS: From July 2015 to November 2017, 50 patients (41 M, 9F), medium age (64 ± 7.4 year) were subject to 33 angioplasties (PTAs) for femoro-popliteal lesions with a paclitaxel-coated balloon (Stellarex™). Based upon clinical data sixteen patients had severe claudication (56% - Rutherford class 3); ten patients suffered from ischemic rest pain (34% - Rutherford class 4); and five presented minor tissue loss (10% - Rutherford class 5). 42% of patients showed femoro-popliteal lesion TASC-II B, and 58% presented lesions pertaining to TASC-II C. RESULTS: Immediate technical success was 100% without perioperative complications. Primary patency rate was 94% at twelve months. In three cases restenosis (6%) was detected within a year from procedure, and a further PTA DCB was performed with primary assisted patency rates of 100% at twelve months. Two patients underwent major lower limb amputation. Three patients died during follow-up and one patient was lost at follow-up. CONCLUSION: DCB angioplasty with Stellarex™ is a viable alternative to traditional endovascular procedures proving satisfactory primary patency rates at twelve months. Based on our experience, treatment with DCB is a first choice technique for non-complex de novo lesions of the femoro - popliteal tract.

Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy.

OBJECTIVE: To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity. DESIGN: Cross-sectional outpatients study. PATIENTS AND METHODS: In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method. RESULTS: Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects. CONCLUSION: We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.

Hospital admission and mortality rates in anorexia nervosa: experience from an integrated medical-psychiatric outpatient treatment.

OBJECTIVES: To evaluate the effectiveness of an integrated medical-psychiatric treatment of major eating disorders. DESIGN: Historical cohort study. SETTING: Outpatient Unit for Protein Energy Malnutrition of the Department of Clinical and Experimental Medicine, "Federico II" University of Naples, time of study: January 1994 to December 1997 PARTICIPANTS: 147 female patients with restrictive or bulimic anorexia nervosa (mean age 19.8 +/- 13.7, BMI 14.7 +/- 2.1 Kg/m2) consecutively attending the outpatient unit between January 1994 and December 1997. MAIN OUTCOME MEASURES: Hospitalization and mortality rates were evaluated up to Jan 1999 with a minimum follow-up of 18 months. RESULTS: There were 23 admissions to the Clinical Nutrition ward for 19 patients (i.e. 12.9%) mostly due to severe protein energy malnutrition, and 2 deaths, only 1 strictly related to anorexia (mortality rate 0.7%). CONCLUSIONS: Integrated outpatient medical-psychiatric treatment for major eating disorders is an effective and inexpensive procedure that reduces mortality and admissions due to medical complications in the medium term.

Protective effects of noradrenaline against tumor necrosis factor-alpha-induced apoptosis in cultured rat brown adipocytes: role of nitric oxide-induced heat shock protein 70 expression.

OBJECTIVE: To elucidate the effects and molecular mechanism(s) by means of which noradrenaline (NA) protects against the tumor necrosis factor (TNF)-alpha-induced apoptosis of brown adipocytes. DESIGN: Brown fat precursor cells were isolated from young rats; 2.5 million cells were added to each 24-well culture plate and cultured in a defined culture medium. On day 8, the cultured cells were exposed to murine recombinant TNF-alpha and/or cycloheximide (CHX; 10 microg/ml) and/or NA and/or nitric oxide (NO) donors and/or the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and/or 10 microM heat shock protein 70 (HSP70) antisense or sense oligomers. MEASUREMENTS: Analysis of DNA fragmentation on agarose gel as a marker of apoptosis; reverse transcriptase-polymerase chain reaction analysis of mRNA levels; Western blotting analysis of protein levels. RESULTS: Pretreatment of primary cultures of rat brown fat cells with micromolar concentrations of NA or the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) induced the expression of HSP70 mRNA and protein, which was associated with cytoprotection against TNF-alpha plus CHX-induced apoptosis. The L-NAME inhibitor of NO synthase activity inhibited both NA-stimulated HSP70 expression and cytoprotection. Furthermore, pretreatment of brown adipocytes with an antisense oligonucleotide to HSP70 antagonized both SNAP- and NA-induced cytoprotection. CONCLUSION: These findings demonstrate that the NO produced by NA stimulation can induce resistance to the TNF-alpha-induced apoptosis of brown adipocytes, possibly by means of the expression of HSP70.