[Effects of Rosa roxburghii on insulin resistance in obese rats and its mechanisms].

Objective: To investigate the effects of Rosa roxburghii on insulin resistance in obese rats and the regulation of phosphatidylinositol 3-kinase (PI3K)/ protein kinase Bß(PKBß/Akt2)/ glucose transporter 4(GLUT4) signaling pathway. Methods: Five-week-old male SD rats were randomly divided into normal control group (NC), model group (M), positive control group (PC), low-dose rosa roxburghii group (LD) and high-dose rosa roxburghii group (HD), with 10 rats in each group. The rats in the NC group were fed with normal diet, while those in the M, PC, LD and HD groups were fed with high-fat diet. From the 13th week, according to the dose standard of 6 ml/kg, rats in the LD group were intragastrically administered with 100 mg/kg Rosa roxburghii Tratt, the HD group were treated with 300 mg/kg Rosa roxburghii Tratt, the PC group were treated with 0.11 g/kg Chiglitazar sodium, and the NC and M groups were intragastrically administered with the same volume of normal saline. The body weight was measured every week until 20 weeks. The rats were sacrificed 24 h after the last experiment. Blood and skeletal muscle were collected. Serum total cholesterol (TC) and triglyceride (TG) contents were detected by colorimetric method, serum superoxide dismutase (SOD) activity was detected by xanthine oxidase method, serum malondialdehyde (MDA) content was detected by thiobarbituric acid method, blood glucose (FBG) value was detected by glucose oxidase method, insulin (FINS) content was detected by ELISA, and PI3K, Akt2, and GLUT4 protein and gene expressions were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with the NC group, the body weight, serum MDA, TG, TC, FBG, FINS, HOMA-IR levels in the M group were significantly increased (P＜0.01), while SOD activity, PI3K、Akt2、GLUT4 protein and mRNA expression levels were significantly increased(P＜ 0.01). Compared with group M, the body weight, serum MDA, TG, TC, FBG, FINS, and HOMA-IR were decreased significantly in LD group, HD group and PC group (P＜0.05 or P＜0.01), while SOD activity, PI3K, Akt2, GLUT4 protein and mRNA expression levels were increased significantly (P＜0.05 or P＜0.01). Conclusion: Rosa roxburghii can improve insulin resistance in obese rats by antioxidant stress and up-regulating the expressions of PI3K, Akt2, and GLUT4 proteins and genes, which may be related to the PI3K/Akt2/GLUT4 signaling pathway.

Endothelin-induced differentiation of Nkx2.5⁺ cardiac progenitor cells into pacemaking cells.

The mechanisms governing the development of cardiac pacemaking and conduction system are not well understood. In order to provide evidence for the derivation of pacemaking cells and the signal that induce and maintain the cells in the developing heart, Nkx2.5(+) cardiac progenitor cells (CPCs) were isolated from embryonic heart tubes of rats. Endothelin-1 was subsequently added to the CPCs to induce differentiation of them towards cardiac pacemaking cells. After the treatment, Nkx2.5(+) CPCs displayed spontaneous beating and spontaneously electrical activity as what we have previously described. Furthermore, RT-PCR and immunofluorescence staining demonstrated that Tbx3 expression was increased and Nkx2.5 expression was decreased in the induced cells 4 days after ET-1 treatment. And the significantly increased expression of Hcn4 and connexin-45 were detected in the induced cells 10 days after the treatment. In addition, Nkx2.5(+) CPCs were transfected with pGCsi-Tbx3 4 days after ET-1 treatment in an attempt to determine the transcription regulatory factor governing the differentiation of the cells into cardiac pacemaking cells. The results showed that silencing of Tbx3 decreased the pacemaking activity and led to down-regulation of pacemaker genes in the induced cells. These results confirmed that Nkx2.5(+) CPCs differentiated into cardiac pacemaking cells after being treated with ET-1 and suggested that an ET-1-Tbx3 molecular pathway govern/mediate this process. In conclusion, our study support the notion that pacemaking cells originate from Nkx2.5(+) CPCs present in embryonic heart tubes and endothelin-1 might be involved in diversification of cardiomyogenic progenitors toward the cells.

Barrett's esophagus and achalasia.

Two unusual cases of achalasia with endoscopic and histologic documentation of Barrett's esophagus are presented. One patient had Barrett's esophagus at the time of initial endoscopy for achalasia, before any treatment. The other patient developed specialized columnar epithelia in the esophagus after treatment with pneumatic dilation. Each patient had evidence of low-grade dysplasia. Including these two patients, 30 cases of Barrett's esophagus in patients with achalasia have been reported in the literature. In 73% (22 of 30) of the cases, Barrett's esophagus was detected after esophagomyotomy. In 20% (6 of 30) of the cases of achalasia and Barrett's esophagus, adenocarcinoma developed. The current two cases are unusual because Barrett's esophagus in achalasia generally develops from gastroesophageal reflux after esophagomyotomy. No other patients have been reported to develop Barrett's esophagus after pneumatic dilation alone. Patients with achalasia and Barrett's esophagus may be at a particularly high risk for developing dysplasia and adenocarcinoma.

Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.