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.     

Plasma Levels of Peptide YY Correlate with Cisplatin-induced Emesis in Dogs

Abstract— The effect of cisplatin on plasma peptide YY (PYY) and 5-hydroxytryptamine (5-HT) concentrations was determined in conscious dogs (n = 6 per group) pretreated with either saline, or the 5-HT₃-receptor antagonists ondansetron or granisetron. Cisplatin (30 mg kg^?1, i.v.) caused emesis (18·8 ± 2·9 episodes; 75–284 min) and significantly increased the mean area under the curve (AUC) over a 6-h period of plasma PYY concentrations (7·4 ± 1·8 to 11·5 ± 3·7 ng) in all saline-pretreated dogs, whereas the mean AUC of plasma 5-HT concentrations did not significantly increase (34·7 ± 7·4 vs 35·6 ± 12·3 pM h). The concentrations of PYY correlated closely with the incidence of emesis (r = 0·99). In animals pretreated (36 min) with ondansetron (0·316 mg kg^?1, i.v.) or granisetron (0·316 mg kg^?1, i.v.), the number of cisplatin-induced emetic episodes was significantly (P < 0·005) decreased compared with control. In animals receiving cisplatin and pretreated with ondansetron, PYY concentrations were not significantly altered, whereas the mean AUC of plasma concentrations of 5-HT over 6 h increased (35·6 ± 12·3 to 82·3 ± 34·6 Pm h; P < 0·05). In animals receiving cisplatin and pretreated with granisetron, plasma concentrations of 5-HT were not significantly altered, whereas the mean AUC of plasma PYY concentrations were significantly reduced compared with control (6·2 ± 1·7 vs 11·5 ± 3·7 ng h). Furthermore, in animals receiving ondansetron without cisplatin treatment, there was no change in the mean AUC of 5-HT or PYY concentrations, whereas the mean AUC of plasma 5-HT concentrations increased significantly (34·7 ± 7·4 to 68·6 ± 37·2 Pm h; P < 0·05) in animals treated with granisetron alone. These studies indicate that plasma concentrations of PYY, and not 5-HT, correlate with cisplatin-induced emesis in dogs. Peptide YY may be an important mediator in cancer chemotherapy-induced emesis and other types of emesis.     

Proarrhythmic and Antiarrhythmic Effects of Flecainide on Nonsustained Reentry Around the Canine Atrial Tricuspid Ring In Vitro

The effect of flecainide, 0.3 mg/L and 1.0 mg/L, on inducible nonsustained reentry was studied, in vitro, in the canine tricuspid ring. Nonsustained reentry was engineered by cutting the ring and reconnecting it with an adjustabJe electronic delay. Delays were used that produced reentry lasting 1–3 beats (group A), 4–10 beats (group B), and 11–25 beats (group C). Reentry was initiated multiple times at each selected delay. A proarrhythmic effect, defined as a significant increase in the duration of reentry, was observed in all 14 trials at the low dose and in two of 15 trials at the high dose in seven experiments. In four more trials a transient proarrhythmic response was seen initially during exposure to the high dose. In five of seven experiments, reentry became sustained after at least one dose of flecainide. Proarrhythmic responses resulted when flecainide increased the tachycardia cycle length more than the effective refractory period and there was less cycle length oscillation after initiation. Antiarrhythmic responses resulted either from a marked increase in effective refractory period at the site of block or production affixed block.     

Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome

Background and Aim: Although increased mast cells in the gut and their role in visceral hypersensitivity in irritable bowel syndrome have been postulated, this relationship remains unclear. Our aim was to determine whether a relationship exists between the number of mucosal mast cells in the gut and visceral hypersensitivity. Method: Eighteen patients with diarrhea predominant irritable bowel syndrome (D‐IBS) (eight females, 10 males aged 25–65 years; mean 42.6 years) with symptoms meeting the Rome‐II criteria, and 15 healthy controls (five females, 10 males aged 31–57 years; mean 41.4 years) were recruited. Participants completed a questionnaire for bowel symptoms and psychological distress. Colonic mucosal mast cells were identified immunohistochemically and quantified by image analysis, and maximally tolerable pressures were evaluated using barostat test. Results: Numbers of mast cells were significantly greater in the terminal ileum, ascending colon and rectum of D‐IBS patients compared with controls (P < 0.01). A multivariate analysis of the barostat test showed that maximally tolerable pressures of D‐IBS patients were significantly lower than those of controls (P < 0.01). When patients were divided into the rectal hypersensitivity (+) and (–) groups by the distension level of 34 mmHg, mast cell counts were significantly higher in the rectal hypersensitivity (–) group than in the rectal hypersensitivity (+) group for the terminal ileum, ascending colon and rectum (P < 0.05, respectively). Conclusions: Rectal sensitivity was enhanced in D‐IBS patients with moderately increased mucosal mast cells, but it was attenuated in patients with markedly increased ones. This study might provide evidence for an important role of mast cells in visceral hypersensitivity.     

Association of active and passive smoking with occupational injury in manual workers: a cross-sectional study of the 2011 Korean working conditions survey

This study was conducted to investigate the relationship of active and passive smoking with occupational injury among manual workers. Data from the 2011 Korean Working Conditions Survey were analyzed for 12,507 manual workers aged ≥15 yr. Overall, 60.4% of men and 5.8% of women were current smokers. The prevalence of injury was higher among never smokers who were exposed to secondhand smoke (SHS) (7.7% in men and 8.1% in women) than current smokers (4.2% in men and 4.1% in women). After controlling for potential confounders, in men, compared to those who never smoked and were not exposed to SHS, people who never smoked and were exposed to SHS (adjusted odds ratio (aOR)=3.7, 2.2–6.4) and current smokers (aOR=2.5, 1.6–3.8) were more likely to experience injury. Among women, the aORs of occupational injury were 8.4 (4.2–16.7) for never smoking women with occasional exposure to SHS and 3.5 (95% CI: 1.4–8.7) for current smokers, in comparison to never smoking women who were never exposed to SHS at work (reference group). The present study suggests that exposure to SHS is a possible risk factor of occupational injury for never smoking men and women.     

单层芯渗透泵片用于水不溶性药物的控制释放单层芯渗透泵片用于水不溶性药物的控制释放

渗透泵片是一种理想的口服控释制剂。国外已将其商品化并依靠它取得了很好的经济效益 ,国内从 2 0世纪 80年代开始研究 ,但是 ,在过渡到工业化时遇到困难[1] 。高速、准确地辨识双层芯渗透泵片的药物层是确保正确打释药孔的必须而又困难的环节 ,也是大规模工业化生产的主要障碍。本文[2 ] 研制的夹芯渗透泵片免去了药物层辨识过程。单层芯渗透泵片既免去药物层辨识过程 ,又简化片芯制备 ,更容易实现工业化生产。本工作研究片芯处方变量对单层芯渗透泵片释药的影响规律。材料与方法药品与仪器、硝苯吡啶定量法和体外释放度测定法等参照文献 [2 ]。单层芯渗透泵片制备　片芯成分在研钵中研磨混匀过 80目筛后 ,直接压成直径 8mm的单层芯片。以 2 5 %醋酸纤维素 (辅以 35 %的聚乙二醇和 5 %的三醋酸甘油酯 )丙酮溶液作包衣液 ,将片芯置于包衣锅内 ,吹入热空气 ,包衣层至 170 μm厚。将包衣片在 6 0℃干燥 2 4h。然后 ,在包衣片两侧各制备一个直径 0 5mm的释药孔。结果与讨论1　聚氧乙烯分子量对释药的影响聚氧乙烯 (PEO)分子质量为 30 0 0 0 0时释药最快 ,10 0 0 0 0和 90...     

Correlation of Electrophysiological Activation Patterns to Tension Generation in Stimulated Latissimus Dorsi Muscle

Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode perse that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions.