[Feeding rhythm entrains circadian metabolism genes, but not the circadian clock, in brown adipose tissue].

The central circadian clock and feeding rhythm coordinately reset peripheral circadian clocks. Emerging evidence suggests that feeding rhythm resets peripheral circadian clocks in a tissue-specific manner. This study aimed to determine whether and how feeding rhythm regulates circadian rhythms of the circadian clock and metabolic genes in brown adipose tissue (BAT). We applied different regimens of time-restricted feeding (TRF) in wildtype and Per1/2 deficient C57BL/6 mice, and quantified the effects of sex, treatment duration, constant light, and circadian clock on circadian rhythms of the BAT circadian clock and metabolic genes by RT-qPCR; Representative circadian clock genes are Bmal1, Nr1d1, Dbp, and Per2, and representative metabolic genes are uncoupling protein 1 (Ucp1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) that controls the flux through glycolysis, pyruvate dehydrogenase kinase isozyme 4 (Pdk4) gating the tricarboxylic acid cycle, and carnitine palmitoyltransferase 1A (Cpt1a) that controls mitochondrial fatty acid oxidation. The results showed that, daytime-restricted feeding (DRF) moderately shifted the phase of the BAT circadian clock in female mice within 7 or 36 d, and resulted in the loss of circadian rhythm in Dbp and Per2 transcripts in males. DRF induced de novo oscillation of the Ucp1 transcript, and shifted the phase of representative metabolic genes, such as Pfkfb3, Pdk4, and Cpt1a, more than 7 h. Constant light is known to disrupt the synchrony of the central circadian clock. The results showed that constant light promoted phase entrainment of the circadian clock by DRF in BAT, but abolished the oscillation of the metabolic genes (except for Pdk4). Despite combined treatment with Per1/2 deficiency and constant darkness, DRF was sufficient to drive circadian rhythms of Bmal1 and Dbp, but not those of Nr1d1, Ucp1, Pfkfb3, and Cpt1a. Overall, the circadian clock of BAT has weak adaptation to altered feeding rhythms and sex differences. The central circadian clock antagonizes DRF in the entrainment of the BAT circadian clock, whereas DRF resets circadian rhythms of metabolic genes, such as Ucp1, Pfkfb3, and Cpt1a, in a circadian clock-dependent manner.

Clinical efficacy and safety of transcatheter closure of ruptured sinus of valsalva aneurysm.

OBJECTIVES: To evaluate the clinical efficacy and safety of transcatheter closure (TCC) in patients with ruptured sinus of Valsalva aneurysm (RSVA). BACKGROUND: RSVA is a rare cardiovascular disease with a varied clinical presentation. The clinical efficacy and safety of TCC for RSVA still remain an ongoing concern. METHODS: From January 2009 to March 2013, 22 patients with RSVA were selected for TCC. Intracardiac pressure and size of cardiac chamber were measured before and post TCC. All patients were followed up by transthoracic echocardiography at 1, 3, 6, 12 months after procedure. RESULTS: RSVA was successfully occluded in 20 patients (19 cases with Amplatzer duct occluder and one with muscular ventricular septal defect occluder). Aortic root angiography showed no shunt in 18 cases and a small residual shunt in two cases. The pressures in the right atrium, right ventricle, and pulmonary artery were significantly decreased after the procedure (P < 0.01), and the aortic pressure was elevated (P < 0.001). The internal diameters of the right atrium, left atrium, and left ventricle were also significantly declined after the procedure (P < 0.05). No complications were found after 18.5 ± 6.5 (range 3-35) months follow-up. Two patients underwent acute surgical aortic valve replacement because of procedure-related aortic valve regurgitation. CONCLUSIONS: Our results indicate that TCC is a promising alternative therapy to surgery in appropriate patients with RSVA. However, rare but severe procedure-related complications should be considered in the risk assessment.

Clinical efficiency and safety analysis of transcatheter closure of multiple atrial septal defects in adults.

BACKGROUND: Transcatheter closure of atrial septal defects (ASDs) is currently a reliable alternative to surgery, even though challenging in patients with multiple ASDs. HYPOTHESIS: The aim of this study was to evaluate the clinical efficiency and safety of transcatheter closure in multiple ASDs. METHODS: Multiple ASDs were diagnosed by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). The occlusive condition and distance between 2 adjacent ASDs were measured by TTE examination. Then, the number and size of the occluder(s) was determined. TTE examinations were performed after transcatheter closure as follow-up. RESULTS: The transcatheter procedure was successful in 15 patients with multiple ASDs, using a single occluder in 9 patients and 2 occluders in the remaining 6 patients. Overall, 21 ASD occluders were implanted. During a follow-up period of 6 mo to 5 y, a slight residual shunt was found in 1 patient without any symptoms; a moderate residual shunt was identified at the inferior vena cava and the occluder was removed by surgery 1 mo after procedure. Other complications, including endocarditis, arrhythmia, thromboembolism, and atrioventricular valve damage were not recorded in any of the 15 patients during the follow-up period. CONCLUSION: Transcatheter closure of multiple ASDs is safe and efficient. Two occluders are necessary for the distance of 2 ASDs more than 7 mm, and a single occluder is sufficient for those 7 mm or less.

[Prognostic impact of heart block during transcatheter closure of ventricular septal defect].

OBJECTIVE: To investigate the prognostic impact of heart block during the transcatheter closure of ventricular septal defect (VSD). METHODS: Forty three patients developed complete left or right bundle branch block (CLBBB, CRBBB), incomplete left or right bundle branch block (ILBBB, IRBBB), and atrioventricular block (AVB) during and within 1 week post procedure were followuped at 1, 6, 12, 24, 36, 48 and 60 months post procedure. Electrocardiogram, dynamic electrocardiogram and transthoracic echocardiography were made. RESULTS: Bundle branch block and atrioventricular block were detected in 26 patients (CLBBB n = 4, CRBBB n = 5, ILBBB n = 2, IRBBB n = 10 and third-degree AVB n = 5) during the transcatheter closure of VSD, and in 17 patients (CLBBB n = 5, CRBBB n = 2, first-degree AVB n = 3, second-degree I-type AVB n = 1 and third-degree AVB n = 6) within 1 week post procedure. Heart block disappeared in 33 patients (76.7%) before discharge, in 37 patients (86.1%) at 1 month and in 41 patients (95.4%) at 6 months post procedure. CLBBB or CRBBB was seen in two cases at 24 months after closure. There was no heart failure and serious cardiac dilatation during follow up. CONCLUSION: The heart block occurred during the periprocedure period of transcatheter closure of VSD was a benign phenomenon without prognostic importance.

Clinical efficiency and safety analysis of transcatheter interventional therapy for compound congenital cardiovascular abnormalities.

OBJECTIVE: To investigate the efficiency and safety of transcatheter interventional therapy for compound congenital cardiovascular abnormalities. METHODS: From Nov 2001 to Jun 2006, a total of 36 patients (17 male, 19 female), aged 17.20 +/- 10.52, with compound congenital cardiovascular abnormalities underwent transcatheter interventional procedure. These patients included 11 with perimembranous ventricular septal defect (PVSD) and patent ductus arteriosus (PDA), 8 patients with PVSD and atrial septal defect (ASD), 8 patients with ASD and PDA, 7 patients with ASD and pulmonary stenosis (PS), 1 patient with ASD and mitral stenosis(MS), 1 patient with coarctation of aorta (COA) and PDA. According to the principle of "easy first, hard second," balloon valvuloplasties of PS or MS were performed before the closure of PVSD, and of PDA and ASD. Electrocardiogram and transthoracic echocardiogram were examined at 4 days, 1, 2, 6 and 12 months, respectively, after each procedure. RESULTS: Transcatheter interventional therapy for compound congenital cardiovascular abnormalities was successful in all patients. Among these, 2 occluders were planted in each of 27 patients, 7 patients with ASD combined with PS and 1 patient with ASD combined with MS underwent successfully performed balloon valvuloplasty and ASD closure, 1 patient with COA combined with PDA underwent successfully performed balloon valvuloplasty and subsequent covered stent implantation. No patient encountered serious adverse events during the (30.5 +/- 14.6) months of follow-up. CONCLUSIONS: Transcatheter interventional therapy for compound congenital cardiovascular abnormalities could obtain satisfactory results with technical feasibility.

Reduced serum levels of oestradiol and brain derived neurotrophic factor in both diabetic women and HFD-feeding female mice.

The estrogen levels in the pre and post menstrual phases interact with brain-derived neurotrophic factor in a complex manner, which influences the overall state of the body. To study the role of oestradiol and brain-derived neurotrophic factor in modulating obesity related type 2 diabetes and the interactions between two factors, we enrolled 15 diabetic premenopausal women and 15 diabetic postmenopausal women respectively, the same number of healthy pre and postmenopausal women were recruited as two control groups. The fasting blood glucose, insulin, lipids, estrogen, and brain-derived neurotrophic factor levels were measured through clinical tests. Additionally, we set up obese female mouse model to mimic human trial stated above, to verify the relationship between estrogen and brain-derived neurotrophic factor. Our findings revealed that there is a moderately positive correlation between brain-derived neurotrophic factor and oestradiol in females, and decreased brain-derived neurotrophic factor may worsen impaired insulin function. The results further confirmed that high fat diet-fed mice which exhibited impaired glucose tolerance, showed lower levels of oestradiol and decreased expression of brain-derived neurotrophic factor mRNA in the ventromedial hypothalamus. The level of brain-derived neurotrophic factor reduced on condition that the level of oestradiol is sufficiently low, such as women in postmenopausal period, which aggravates diabetes through feeding-related pathways. Increasing the level of brain-derived neurotrophic factor may help to alleviate the progression of the disease in postmenopausal women with diabetes.