Carotid Artery Revascularization Improves Cardiac Sympathetic Nerve Activity in Patients With Carotid Artery Stenosis

Background: The carotid sinus baroreceptor reflex controls the neural regulation of blood pressure. Baroreceptor disorders due to carotid sinus atherosclerosis have detrimental cardiovascular effects. This study investigated the medium-term effects of carotid artery revascularization (CAR) on sympathetic and cardiac function and systemic blood pressure variability in patients with carotid artery stenosis.Methods: This study included 21 consecutive patients (median age 70 years, 18 men) with carotid artery stenosis scheduled for CAR. 123I metaiodobenzylguanidine (MIBG) scintigraphy, echocardiography, brain natriuretic peptide levels, 24-h Holter electrocardiography (ECG), and ambulatory blood pressure monitoring assessed approximately 3 months postoperatively were compared to preoperative data.Results: All 21 enrolled patients underwent CAR. Carotid artery stenting was done in three patients with cardiovascular risk or anatomical difficult for carotid endarterectomy. The mean common carotid artery end-diastolic velocity improved significantly (P < 0.01) by 1.6-fold, from 10.8 ± 3.2 to 16.1 ± 7.1 cm/s. In 123I-MIBG scintigraphy, the heart-to-mediastinum (H/M) count ratio was significantly higher than preoperatively (from 2.66 ± 0.48 to 2.86 ± 0.56, P = 0.03). Holter ECG analysis revealed a significant decrease in the low-frequency/high-frequency (LF/HF) ratio compared to preoperatively (from 2.17 ± 1.20 to 1.62 ± 0.68, P = 0.04). These findings suggest decreased myocardial sympathetic activation. In echocardiography, the tissue Doppler-derived e’ increased, and E/e’ decreased significantly (P < 0.05) from 11.7 ± 5.1 to 10.1 ± 4.0, suggesting an improved left ventricular diastolic capacity. The mean 24-h and nighttime blood pressures were unchanged.Conclusions: CAR in patients with carotid stenosis may provide medium-term improvement in cardiac sympathetic nerve activity and left ventricular diastolic dysfunction

A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud

AbstractMammal–fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements

Altered balance of epidermis-related chemokines in epidermolysis bullosa

Background: Epidennolysis bullosa (EB) is a congenital, refractory skin disease and there are no fundamental treatments. Recently, allogenic cell therapies are beginning to be applied as potential treatments, that are based on the concept that the allogenic cells can migrate into the skin and reconstitute the skin components. Although the mechanisms of cell migration into skin are not fully understood, chemokines are regarded as key factors in recruiting bone marrow-derived cells. Objectives: Our study aims to elucidate the expression of chemokines in the EB patients. Methods: We determined the expression of wound-healing related chemokines in the sera, keratinocytes, and skin tissues of EB patients and compared them to those of healthy volunteers by enzyme-linked immunosorbent assays, quantitative reverse transcription PCR, and immunofluorescence staining. Results: The serum levels of CXCL12 and HMGB1 were found to be significantly elevated in the EB patients. Conversely, the serum levels of CCL21 were found to be lower in the EB patients than in healthy controls. In addition, the serum levels of CXCL12 tended to increase and the serum levels of CCL27 tended to decrease with an increase in the affected body surface areas. To detect the origin of the circulating chemokines, we performed immunofluorescence staining. CCL21, CCL27, HMGB1 and CXCL12 were stained more broadly in the EB patient tissues than those in the control tissues. Conclusions: These results suggest that fluctuations in chemokine levels may contribute in a coordinated way to the wound-healing process and lend clues toward efficient cell therapies for EB

Food intake patterns and cardiovascular risk factors in Japanese adults: analyses from the 2012 National Health and nutrition survey, Japan

Abstract Background There is an increasing global interest in the role of Japanese diet as a possible explanation for the nation’s healthy diet, which contributes to the world’s highest life-expectancy enjoyed in Japan. However, nationwide studies on current food intake status among general Japanese population have not been established yet. This study examined the association between food intake patterns and cardiovascular risk factors (CVRF) such as waist circumference (WC), body mass index (BMI), blood pressure (SBP, DBP), HbA1c and blood lipid profiles among general Japanese adults. Methods De-identified data on the Japan National Health and Nutrition Survey (NHNS) 2012 with a total of 11,365 subjects aged 20–84 years were applied. Food intake patterns were derived by principal component analysis (PCA) based on 98 food groups. Generalized linear regression analysis was used to assess the relation between the food intake patterns and CVRF. Results We identified three food intake patterns: traditional Japanese, Westernized, and meat and fat patterns. Traditional Japanese pattern was significantly related to high WC and BMI in men, and high DBP in women. Westernized pattern was associated with lower SBP, but high total cholesterol and LDL cholesterol in both men and women. Meat and fat pattern was associated with high WC, high BMI, high blood pressure and blood lipid profiles in both men and women (trend P < 0.001). Conclusion The significant association between cardiovascular disease risks and three food intake patterns derived from the NHNS, showed a similar tendency to other dietary survey methods

The Anti-Adiposity Mechanisms of Ampelopsin and Vine Tea Extract in High Fat Diet and Alcohol-Induced Fatty Liver Mouse Models

Ampelopsis grossedentata (AG) is an ancient medicinal plant that is mainly distributed and used in southwest China. It exerts therapeutic effects, such as antioxidant, anti-diabetic, and anti-inflammatory activities, reductions in blood pressure and cholesterol and hepatoprotective effects. Researchers in China recently reported the anti-obesity effects of AG extract in diet-induced obese mice and rats. To verify these findings, we herein investigated the effects of AG extract and its principal compound, ampelopsin, in high-fat diet (HFD)- and alcohol diet-fed mice, olive oil-loaded mice, and differentiated 3T3-L1 cells. The results obtained showed that AG extract and ampelopsin significantly suppressed increases in the weights of body, livers and abdominal fat and also up-regulated the expression of carnitine palmitoyltransferase 1A in HFD-fed mice. In olive oil-loaded mice, AG extract and ampelopsin significantly attenuated increases in serum triglyceride (TG) levels. In differentiated 3T3-L1 cells, AG extract and ampelopsin promoted TG decomposition, which appeared to be attributed to the expression of hormone-sensitive lipase. In alcohol diet-fed mice, AG extract and ampelopsin reduced serum levels of ethanol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) and liver TG. An examination of metabolic enzyme expression patterns revealed that AG extract and ampelopsin mainly enhanced the expression of aldehyde dehydrogenase and suppressed that of cytochrome P450, family 2, subfamily e1. In conclusion, AG extract and ampelopsin suppressed diet-induced intestinal fat accumulation and reduced the risk of fatty liver associated with HFD and alcohol consumption