Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing beta(2)-adrenergic receptors in the heart

OBJECTIVE: To explore long-term cardiac phenotype in transgenic (TG) mice with 300-fold overexpression of beta(2)-adrenergic receptors (AR). METHODS: Echocardiography was performed serially on a cohort of wild-type and TG mice (n=26 each) between 4 and 15 months of age. Survival was monitored and autopsy and histological examinations were performed. RESULTS: Heart rate was higher in TG than in wild-type mice throughout the study period. The left ventricular dimensions and fractional shortening were similar between TG and wild-type groups during 4-6 months. Starting at 9 months, however, TG mice showed progressive reduction in fractional shortening and systolic wall thickening, and increase in left ventricular dimensions and left ventricular mass, indicating onset of heart failure, left ventricular hypertrophy and remodeling. Abnormal waveforms in the electrocardiogram and episodes of ventricular ectopic beats were also observed in TG mice. Death of TG mice started at 8.5 months, and the cumulative mortality was 81% by 15 months (P<0.0001 vs. 4% in wild-type mice). The majority of deaths were due to severe heart failure, indicated by cardiac dilatation, lung congestion, pleural effusion and atrial thrombus. Left ventricular sections showed widespread interstitial fibrosis, loss of myocytes and myocyte hypertrophy in TG mice. CONCLUSIONS: A high level of beta(2)AR overexpression results in cardiomyopathy and heart failure. The onset was slower and the expression levels of receptors required are much higher than previously described for the beta(1)AR overexpression.     

Dynamic and ultrastructural study of sphincter of Oddi in early-stage cholelithiasis in rabbits with hypercholesterolemia

AIM To study the relationship between preformation of gallstone and the kinetics and ultrastructure of sphincter of Oddi.METHODS Adult female rabbits were used and divided into 3 groups, and fed with either normal or high cholesterol diet for four or eight weeks.Each group contained eight rabbits. The manometry of sphincter of Oddi, biliary cineradiography, gallbladder volume measurement and ultrastructure observation under electron microscope were performed.RESULTS In groups Ⅰ and Ⅱ, the basal pressure in low-pressure ampulla or high pressure zone of sphincter of Oddi was elevated, the amplitude of phasic contraction was decreased and the volume of gallbladder were increased, with a significant difference (P＜0.01) from those of control. Gallstones were found in group Ⅱ rabbits (7/8). Under cineradiography, low-pressure ampulla showed a spasmodic status without apparent peristaltic contraction. Under electron microscope, inside the muscular cells of sphincter of Oddi,loosening of microfilament and swelling of plasmosomes which congregated at the top were observed. The amount showed no obvious change under nitric oxide synthase (NOS) stain.CONCLUSION Twisting of the microfilament and disarrangement of kink macula densa inside the muscular cells suggested that the sphincter of Oddi was under spasmodic status. The impaired diastolic function caused and aggravated the stasis of cystic bile. The swelling plasmosome could be one of the important factors in elevating the tonic pressure of sphincter of Oddi.     

内科疾病对非心脏手术病人术中心血管并发症的影响

目的 探讨老年非心脏手术病人合并的内科疾病对术中心血管并发症的影响。方法 回顾分析３０８８例老年非心脏手术病人的临床资料。结果 合并各种内科疾病的老年人术中心血管并发症的发生率明显高于正常老年人组,其中以慢支和９或）合并肺气肿及心绞痛病人术中心智力这并发症发病率最高。心电图及超声心动图检查结果阳性的病人术中心血和并发症的发病率明显增高。结论 老年人合并各种内科疾病均可明显增加术中心血管并发症发生,     

MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands

Toll-like receptors (TLRs) trigger intestinal inflammation when the epithelial barrier is breached by physical trauma or pathogenic microbes. Although it has been shown that TLR-mediated signals are ultimately protective in models of acute intestinal inflammation [such as dextran sulfate sodium (DSS)-induced colitis], it is less clear which cells mediate protection. Here we demonstrate that TLR signaling in the nonhematopoietic compartment confers protection in acute DSS-induced colitis. Epithelial cells of MyD88/Trif-deficient mice express diminished levels of the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG), and systemic lipopolysaccharide administration induces their expression in the colon. N-ethyl-N-nitrosourea (ENU)-induced mutations in Adam17 (which is required for AREG and EREG processing) and in Egfr both produce a strong DSS colitis phenotype, and the Adam17 mutation exerts its deleterious effect in the nonhematopoietic compartment. The effect of abrogation of TLR signaling is mitigated by systemic administration of AREG. A TLR→MyD88→AREG/EREG→EGFR signaling pathway is represented in nonhematopoietic cells of the intestinal tract, responds to microbial stimuli once barriers are breached, and mediates protection against DSS-induced colitis.     

Role of serotonin in development of esophageal and gastric fundal varices

AIM:To determine the effect of free serotonin concentrations in plasma on development of esophageal and gastric fundal varices. METHODS:This prospective study included 33 patients with liver cirrhosis and 24 healthy controls. Ultrasonography and measurement of serotonin concentration in plasma were carried out in both groups of subjects. The upper fiber panendoscopy was performed only in patients with liver cirrhosis. RESULTS:The mean plasma free serotonin levels were much higher in liver cirrhosis patients than in healthy controls (219.0 ± 24.2 nmol/L vs 65.4 ± 18.7 nmol/L,P < 0.0001). There was no significant correlation be-tween serotonin concentration in plasma and the size of the esophageal varices according to Spearman coefficient of correlation (rs =-0.217,P > 0.05). However,the correlation of plasma serotonin concentration and gastric fundal varices was highly significant (rs =-0.601,P < 0.01). CONCLUSION:Free serotonin is significant in pathogenesis of portal hypertension especially in development of fundal varices,indicating the clinical value of serotonergic receptor blockers in these patients.     

An Unusual Case of Congenitally Unguarded Tricuspid Valve Orifice Associated with Pulmonary Valve Atresia and Intact Ventricular Septum

We report on a premature neonate who presented with cyanosis soon after birth. She was found on echocardiography to have an unguarded tricuspid valve orifice associated with pulmonary valve atresia and an intact interventricular septum. Owing to the small‐sized pulmonary arteries, she was initially managed conservatively with prostaglandin infusion, and at one year of age underwent a successful bidirectional cavo‐pulmonary (Glenn) shunt operation. (ECHOCARDIOGRAPHY 2010;27:202‐204)     

Self-assembled artificial cilia

Due to their small dimensions, microfluidic devices operate in the low Reynolds number regime. In this case, the hydrodynamics is governed by the viscosity rather than inertia and special elements have to be introduced into the system for mixing and pumping of fluids. Here we report on the realization of an effective pumping device that mimics a ciliated surface and imitates its motion to generate fluid flow. The artificial biomimetic cilia are constructed as long chains of spherical superparamagnetic particles, which self-assemble in an external magnetic field. Magnetic field is also used to actuate the cilia in a simple nonreciprocal manner, resulting in a fluid flow. We prove the concept by measuring the velocity of a cilia-pumped fluid as a function of height above the ciliated surface and investigate the influence of the beating asymmetry on the pumping performance. A numerical simulation was carried out that successfully reproduced the experimentally obtained data.     

Effects of three antidiabetics on insulin and leptin in Chinese type 2 diabetes

AimsThis study was to investigate the effects of some different antidiabetics on circulating insulin and leptin levels in type 2 diabetes with or without overweight in a Chinese population.Methods80 type 2 diabetes men with overweight (body mass index BMI > 24 kg/m²) and 35 type 2 diabetes men with normal body weight (BMI ≤ 24 kg/m²) and 56 control subjects were enrolled in the study. We measured blood glucose, insulin, leptin, total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose, postprandial glycose, HbA1c and BMI before and after the administration of antidiabetic drugs.ResultsCompared with normal body weight, the levels of plasma insulin and leptin in overweight type 2 diabetes men were higher, after 3 months treatment, a significant increase in insulin and leptin levels was observed in overweight type 2 diabetes men in gliclazide group. Levels of leptin and insulin decreased in metformin and rosiglitazone groups, respectively.ConclusionsWe conclude that surfonylureas treatment leads to increased insulin and leptin levels in overweight type 2 diabetes men, metformin, or rosiglitazone treatment can reduce insulin and leptin levels, respectively, and effect of metformin on plasma leptin and insulin levels is more significant than that of rosiglitazone.     

Incidence of potential glycosylation sites in immunoglobulin variable regions distinguishes between subsets of Burkitt's lymphoma and mucosa-associated lymphoid tissue lymphoma

Recently, a high incidence of novel N-glycosylation sites introduced by somatic mutation was observed in the immunoglobulin variable region genes of follicular lymphoma. As these are positively selected and are uncommon in normal B cells, they may have a role in tumour growth and behaviour. Sites are not characteristic of chronic lymphocytic leukaemia or myeloma, but are detectable in approximately 50% of diffuse large cell lymphomas. Another feature of the variable region genes of certain lymphomas is ongoing somatic mutation. To determine whether glycosylation is associated with this phenomenon, we analysed variable region gene sequences of Burkitt's lymphoma (BL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Novel sites were common in endemic BL (82%) and in 4/5 patients with Iranian BL. However, sporadic BL had a lower incidence (43%). Patients with MALT lymphoma had a low frequency (9%) of novel sites, comparable to normal B cells. These findings distinguish glycosylation sites from ongoing mutation and may reflect different environmental influences on these tumours.