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Background and Purpose: Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of β-adrenoceptor antagonist (β-blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. β-Blockers have been shown to reduce SNS hyperactivity in HF, but the underlying molecular mechanisms are not understood. The GPCR kinase-2 (GRK2)-α(2) adrenoceptor-catecholamine production axis is up-regulated in the adrenal medulla during HF causing α(2) -adrenoceptor dysfunction and elevated catecholamine levels. Here, we sought to investigate if β-blocker treatment in HF could lower SNS activation by directly altering adrenal GRK2 levels.Experimental Approach: Four weeks after myocardial infarction-induced HF, adult rats were randomized to 10-week treatment with vehicle (HF/C) or bisoprolol (HF/B). Cardiac function and dimensions were measured. In heart and adrenal gland, GRK2 levels were assessed by RT-PCR and Western blotting and adrenoceptors studied with radioligand binding. Catecholamines and α(2) adrenoceptors in adrenal medulla chromaffin cell cultures were also measured.Key Results: Bisoprolol treatment ameliorated HF-related adverse cardiac remodelling and reduced plasma catecholamine levels, compared with HF/C rats. Bisoprolol also attenuated adrenal GRK2 overexpression as observed in HF/C rats and increased α(2) adrenoceptor density. In cultures of adrenal medulla chromaffin cells from all study groups, bisoprolol reversed HF-related α(2) adrenoceptor dysfunction. This effect was reversed by GRK2 overexpression.Conclusion and Implications: Blockade of β-adrenoceptors normalized the adrenal α(2) adrenoceptor-catecholamine production axis by reducing GRK2 levels. This effect may contribute significantly to the decrease of HF-related sympathetic overdrive by β-blockers. [ABSTRACT FROM AUTHOR]

Background and Purpose: We investigated whether β(2) -adrenoceptor overexpression could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodeling of the failing heart.Experimental Approach: We explored the angiogenic effects of β(2) -adrenoceptor overexpression in a rat model of post-myocardial infarction (MI) heart failure (HF). Cardiac adenoviral-mediated β(2) -adrenoceptor overexpression was obtained via direct intramyocardial injection 4-weeks post-MI. Adenovirus(Ad)-GFP and saline injected rats served as controls. Furthermore, we extended our observation to β(2) -adrenoceptor -/- mice undergoing MI.Key Results: Transgenes were robustly expressed in the LV at 2 weeks post-gene therapy, whereas their expression was minimal at 4-weeks post-gene delivery. In HF rats, cardiac β(2) -adrenoceptor overexpression resulted in enhanced basal and isoprenaline-stimulated cardiac contractility at 2-weeks post-gene delivery. At 4 weeks post-gene transfer, Ad-β(2) -adrenoceptor HF rats showed improved LV remodeling and cardiac function. Importantly, β(2) -adrenoceptor overexpression was associated with a markedly increased capillary and arteriolar length density and enhanced in vivo myocardial blood flow and coronary reserve. At the molecular level, cardiac β(2) -adrenoceptor gene transfer induced the activation of the VEGF/PKB/eNOS pro-angiogenic pathway. In β(2) -adrenoceptor-/- mice, we found a ~25% reduction in cardiac capillary density compared with β(2) -adrenoceptor+/+ mice. The lack of β(2) -adrenoceptors was associated with a higher mortality rate at 30 days and LV dilatation, and a worse global cardiac contractility compared with controls.Conclusions and Implication: β(2) -Adrenoceptors play an important role in the regulation of the angiogenic response in HF. The activation of VEGF/PKB/eNOS pathway seems to be strongly involved in this mechanism. [ABSTRACT FROM AUTHOR]

Background Lifestyle interventions are often ineffective in the treatment of pediatric obesity. Weight loss devices have been introduced for the temporary nonsurgical treatment of morbid obesity. Objective The aim of the study is to evaluate the efficacy of Obalon Intragastric Balloon on weight loss and on metabolic and cardiovascular parameters in a pediatric population with severe obesity. Methods We enrolled 10 children with severe obesity. In all patients anthropometric parameters, biochemical tests, ultrasound liver examination and blood pressure monitoring were evaluated at the time of insertion and after removal of device. Results The Obalon had a positive effect on decrease of weight, body mass index and percentage of excess body weight within 3 months from placement. Moreover, this safe minimally invasive device improves the cardio-metabolic profiles of obese children. Conclusions The Obalon could be a useful tool in the difficult management of pediatric patients with morbid obesity, inducing in short-term a meaningful weight loss. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma ( HCC) may develop from non-alcoholic fatty liver disease ( NAFLD) either in the presence or in the absence of established cirrhosis. Non-cirrhotic patients with NAFLD-related HCC are usually adult, male and obese. However, this association has not been reported yet in younger age groups. Objectives In the present study, the clinical case of a 7-yaer-old obese boy with steatosis and HCC is presented. Methods A 7-year-old boy, with no evidence of chronic liver disease, was admitted for assessment of a liver mass. Preliminary assessment was suggestive of a combined and severe liver steatosis together with a malignant disease. Results A biopsy confirmed the suspected diagnosis of HCC; interestingly, the non-neoplastic liver was surrounded and characterized by the presence of steatosis and ballooning, and being absent of lobular inflammation and fibrosis. Chemotherapy and diet changes were conducted successfully with ultrasound characteristics suggesting improvements on both aspects: conventional liver mass resection could take place. Conclusions This case report suggests that HCC might develop in paediatric age patients with obesity-related NAFLD, even in the absence of fibrosis. [ABSTRACT FROM AUTHOR]

The management of de novo hepatitis B ( HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of β-adrenoceptor antagonist (β-blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. β-Blockers have been shown to reduce SNS hyperactivity in HF, but the underlying molecular mechanisms are not understood. The GPCR kinase-2 (GRK2)-α2adrenoceptor-catecholamine production axis is up-regulated in the adrenal medulla during HF causing α2-adrenoceptor dysfunction and elevated catecholamine levels. Here, we sought to investigate if β-blocker treatment in HF could lower SNS activation by directly altering adrenal GRK2 levels. EXPERIMENTAL APPROACH Four weeks after myocardial infarction-induced HF, adult rats were randomized to 10-week treatment with vehicle (HF/C) or bisoprolol (HF/B). Cardiac function and dimensions were measured. In heart and adrenal gland, GRK2 levels were assessed by RT-PCR and Western blotting and adrenoceptors studied with radioligand binding. Catecholamines and α2adrenoceptors in adrenal medulla chromaffin cell cultures were also measured. KEY RESULTS Bisoprolol treatment ameliorated HF-related adverse cardiac remodelling and reduced plasma catecholamine levels, compared with HF/C rats. Bisoprolol also attenuated adrenal GRK2 overexpression as observed in HF/C rats and increased α2adrenoceptor density. In cultures of adrenal medulla chromaffin cells from all study groups, bisoprolol reversed HF-related α2adrenoceptor dysfunction. This effect was reversed by GRK2 overexpression. CONCLUSION AND IMPLICATIONS Blockade of β-adrenoceptors normalized the adrenal α2adrenoceptor-catecholamine production axis by reducing GRK2 levels. This effect may contribute significantly to the decrease of HF-related sympathetic overdrive by β−blockers. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE We investigated whether β2-adrenoceptor overexpression could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodeling of the failing heart. EXPERIMENTAL APPROACH We explored the angiogenic effects of β2-adrenoceptor overexpression in a rat model of post-myocardial infarction (MI) heart failure (HF). Cardiac adenoviral-mediated β2-adrenoceptor overexpression was obtained via direct intramyocardial injection 4-weeks post-MI. Adenovirus(Ad)-GFP and saline injected rats served as controls. Furthermore, we extended our observation to β2-adrenoceptor −/− mice undergoing MI. KEY RESULTS Transgenes were robustly expressed in the LV at 2 weeks post-gene therapy, whereas their expression was minimal at 4-weeks post-gene delivery. In HF rats, cardiac β2-adrenoceptor overexpression resulted in enhanced basal and isoprenaline-stimulated cardiac contractility at 2-weeks post-gene delivery. At 4 weeks post-gene transfer, Ad-β2-adrenoceptor HF rats showed improved LV remodeling and cardiac function. Importantly, β2-adrenoceptor overexpression was associated with a markedly increased capillary and arteriolar length density and enhanced in vivo myocardial blood flow and coronary reserve. At the molecular level, cardiac β2-adrenoceptor gene transfer induced the activation of the VEGF/PKB/eNOS pro-angiogenic pathway. In β2-adrenoceptor−/− mice, we found a ∼25% reduction in cardiac capillary density compared with β2-adrenoceptor+/+ mice. The lack of β2-adrenoceptors was associated with a higher mortality rate at 30 days and LV dilatation, and a worse global cardiac contractility compared with controls. CONCLUSIONS AND IMPLICATION β2-Adrenoceptors play an important role in the regulation of the angiogenic response in HF. The activation of VEGF/PKB/eNOS pathway seems to be strongly involved in this mechanism. [ABSTRACT FROM AUTHOR]

A correction to the article "Obalon intragastric balloon in the treatment of paediatric obesity: a pilot study" is presented about one of the author names.