吉非罗齐对实验性糖尿病大鼠的降糖作用及其机制研究

 目的观察吉非罗齐(gemfibrozil,Gem)对实验性2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠的降糖、降脂作用及其可能机制。方法采用高糖高脂膳食4周诱导大鼠胰岛素抵抗后,腹腔注射亚致病剂量链脲佐菌素(streptozotocin,STZ)的方法制备T2DM模型,并观察Gem对其血脂、血糖代谢的影响及其可能机制。结果连续灌胃给药8周后,Gem显著降低实验性糖尿病大鼠的空腹血糖(fasting blood glucose,FBG)和三酰甘油(triglyceride,TG)、总胆固醇(totalcholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)及游离脂肪酸含量(nonesterified fatty acid,NEFA)(P<0.05或P<0.01),显著增高实验性糖尿病大鼠血清SOD活力(superoxide dismutase,SOD),降低模型组大鼠MDA(maleic dialdehyde,MDA)含量(P<0.05或P<0.01)。结论Gem不仅对实验性T2DM大鼠血脂具有良好的调节作用,还能改善实验性T2DM大鼠的血糖代谢,显著降低FBG。     

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation

Abstract In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS ( P < 0.05) or tubercle bacilli ( P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1β, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.     

The Relationship Between Endocardial Voltage and Regional Volume in Electroanatomical Remodeled Left Atria in Patients with Atrial Fibrillation: Comparison of Three‐Dimensional Computed Tomographic Images and Voltage Mapping

Background: Long‐standing atrial fibrillation (AF) changes left atrial (LA) morphology, and the LA size is related to recurrence after radiofrequency catheter ablation (RFCA). We hypothesize that LA morphology, based on embryological origin, affects the outcome of RFCA. Methods: We analyzed 3D computed tomographic (CT) images of LA in 70 patients with AF (54 males, 55.6 ± 10.5 years old, paroxysmal AF (PAF):persistent AF (PeAF) = 32:38) who underwent RFCA. Each LA image was divided into venous atrium (VA), anterior LA (ALA), LA appendage (LAA), and both antrum. Absolute and relative volumes were calculated, and the lengths of linear ablation sites were measured. Results: (1) In patients with the mean LA voltage ≤ 2.0 mV, LA volume, especially ALA, was larger (P < 0.01) compared to those with LA voltage > 2.0 mV. (2) The total LA volume was significantly larger (P < 0.01) and LAA voltages (P < 0.05) and conduction velocities (P < 0.05) were lower in patients with PeAF than in those with PAF. (3) In patients with recurrence, LA volume was generally larger (P < 0.01) than in those without recurrence. In PAF patients with recurrence, the relative volume of ALA was significantly larger (P < 0.01) than those without recurrence. Conclusions Morphologically remodeled LA has low endocardial voltage, and enlargement of ALA is more significant in electroanatomically remodeled LA. The disproportional enlargement of ALA was observed more often in PAF patients with recurrence after ablation than those without recurrence.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

Dual Sensor VVIR Mode Pacing: Is It Worth It?

Dual sensor ventricular demand rate responsive (VVIR mode) pacing was compared with single sensor rate responsive pacing to assess whether this new development should be more widely incorporated in modern pacemaker devices. A within patient randomized, double-blind crossover study involving ten patients, mean age 67.4 years (70% male), had Medtronic Legend Plus dual sensor VVIR pacemakers implanted for high grade A V block and chronic or persistent paroxysmal atrial fibrillation. Performance values were compared to 20 healthy control subjects of a similar age and gender. Patients were both subjectively and objectively assessed after 2 weeks of out-of-hospital activity in VVIR mode (minute ventilation sensing), VVIR mode (activity sensing), VVIR mode (dual sensor), and VVI mode (no rate response). All patients were assessed for subjective preference for, and objective improvement in, any pacing modality as assessed by standardized daily activity protocols and graded exercise treadmill testing. Subjective perception of exercise capacity and functional status was significantly lower in VVI mode (P < 0.05) compared to any of the VVIR modes, which did not differ. After completion of the study 70% of patients chose VVIR as their preferred mode, with 30% expressing no preference. Forty percent preferred activity sensor WIR mode pacing, 30% preferred dual sensor VVIR mode pacing, and 70% found either dual sensor WIR mode, minute ventilation sensor WIR mode, or both modalities least acceptable. No patient found activity sensing WIR mode least acceptable. Graded treadmill testing revealed significantly lower exercise tolerance during WI mode pacing (P < 0.01) compared to the VVIR modalities, which did not differ. Overall, chronotropic response was best with dual sensor pacing during standardized daily activity protocols and during the standard car journey. The data from this study suggest that there is no marked clinical advantage obtained from the use of dual sensor devices over current activity sensing ventricular demand rate responsive pacemakers, but with the probable added disadvantages of increased size, complexity, cost, and decreased longevity.     

Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers

Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers. APMIS 2009; 117: 880–5. Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia‐inducible factor 1α (HIF1α) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1α is upregulated not only by hypoxia but also by genetic alterations in HIF1α‐related genes, including VHL. Cullin 2 (CUL2) interacts with the trimeric VHL‐elongin B‐elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1α. The aim of this study was to explore whether HIF1α and CUL2 genes are somatically mutated, and contribute to HIF1α activation in common human cancers. For this, we have analyzed the coding region of oxygen‐dependent degradation domain of HIF1α in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single‐strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in CUL2 in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one HIF1α mutation (p.Ala593Pro) in the hepatocellular carcinomas (1/47; 2.1%), but none in other cancers. We found two CUL2 frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2/41). Our data indicate that somatic mutation of HIF1α is rare in common cancers, and somatic mutation of CUL2 occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither HIF1α nor CUL2 mutation may play a central role in HIF1α activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.     

Bronchoscopic features and bronchoscopic intervention for endobronchial hamartoma

Background and objective: Bronchoscopic resection of endobronchial hamartomas has been reported to have a favourable outcome. This study describes the bronchoscopic features of endobronchial hamartoma and reports the clinical outcome of bronchoscopic intervention. Methods: A retrospective analysis was conducted of patients with histologically proven endobronchial hamartomas, diagnosed in the 10‐year period 1999–2009 to elucidate the clinical, radiological and bronchoscopic features of hamartoma and to describe the clinical outcomes. Results: Seventeen of the 135 patients with pulmonary hamartomas were diagnosed as having endobronchial hamartomas. CXR was abnormal in 11 of the 17 patients. On chest CT (n = 16), the median diameter of the lesion was 15.6 mm. Calcification and areas of focal fat in the lesion, the diagnostic CT findings of pulmonary hamartoma, were found in two of 16 (12.5%) patients. At bronchoscopy (n = 16), all tumours had a mass appearance and most were smooth surfaced round masses (50.0%) with 18.8% having a ‘stalk’. Bronchoscopic forceps biopsies were performed in 13 patients, which resulted in five patients (38.5%) being diagnosed with endobronchial hamartoma. Fifteen patients were treated with rigid or flexible bronchoscopic resection, one had lobectomy, and one had no intervention. No procedure‐related mortalities or late complications developed. Conclusions: Bronchoscopic intervention appears to be a safe and effective method to resect endobronchial hamartomas.