Bee-Song Chang

Cysteinyl leucotriene receptor type 1 mediates contraction in human and guinea‐pig oesophagus

Abstract  Leucotriene D4 (LTD4) causes contraction of the guinea‐pig and cat oesophagus. Effects of cysteinyl leucotrienes in the human oesophagus were unknown. To investigate and compare the cysteinyl leucotriene effects in the human oesophagus with those in the guinea‐pig oesophagus, we measured contraction of muscularis mucosae strips isolated from the human and guinea‐pig oesophagus caused by cysteinyl leucotrienes, LTC4, LTD4 and LTE4, as well as the dihydroxy leucotriene, LTB4. Effects of leucotrienes in human were similar to those in guinea‐pig oesophagus. LTC4 and LTD4 caused moderate, whereas LTE4 caused mild, concentration‐dependent contraction. LTE4 was a partial agonist. In contrast, LTB4 did not cause any contraction. The relative potencies for cysteinyl leucotrienes to cause contraction were LTD4 = LTC4 > LTE4. The LTD4‐induced contraction was moderately inhibited by two selective CysLT1 receptor antagonists, montelukast and zafirlukast, in both human and guinea‐pig oesophagus. In addition, the LTD4‐induced contraction was not and only slightly inhibited by BAY u9773, the CysLT1 and CysLT2 receptor antagonist, in the human and guinea‐pig oesophageal muscularis mucosae respectively. These indicate the existence of the CysLT1 mediating oesophageal contraction in both human and guinea‐pig oesophagus. The LTD4‐induced contraction was not affected by tetrodotoxin, atropine or capsaicin, suggesting a direct effect. These results demonstrate that cysteinyl leucotrienes but not the dihydroxy leucotriene cause contraction in the human and guinea‐pig oesophagus. CysLT1 mediates contraction in both human and guinea‐pig oesophagus.

Quality Improvements of Antimicrobial Prophylaxis in Coronary Artery Bypass Grafting

BACKGROUND Although the principles of antibiotics prophylaxis are well established, more than 60% of hospitals that joined the international quality indicator project failed to discontinue the use of prophylactic antibiotics within 24h after coronary artery bypass grafting (CABG). Our specific aims are to disseminate the gain obtained from breakthrough series model in knee arthroplasty and abdominal hysterectomy to increase the rate of prophylactic duration not longer than 24h in patients with CABG. METHODS The control and intervention groups enrolled 55 and 78 patients with CABG before and after the project. Measurements were prophylactic interval and duration, surgical site infection, hospital and antibiotics costs. Two strategies were developed. The key cardiac surgeon was invited to attend quality improvement activities. Knowledge and rationale of medical quality indicators would thus be communicated. Secondly, we proposed a regional symposium in which a level of competition was subconsciously established, and practitioners would present their level of compliance. RESULTS Instances of prophylactic interval within 1h prior to incision were significantly increased from 66.7% to 97.4%. Rates of prophylactic duration less than 24h were significantly increased from 2.8% to 66.1%. The average hospital cost was reduced by 16.4%, and antibiotics cost was reduced by 91.8%. No significant changes in surgical site infection within 30 d of CABG were observed. CONCLUSIONS We successfully disseminated the gain of breakthrough project in improving antimicrobial prophylaxis to CABG. By implementing this model, we are able to optimize the timing and duration of antimicrobial prophylaxis in patients with CABG to a level above worldwide average.

Endothelin causes contraction of human esophageal muscularis mucosae through interaction with both ETA and ETB receptors

Abstract Endothelin (ET) causes contraction of the muscularis mucosae in the guinea pig esophagus, but its role in the human esophagus remains unknown. To investigate effects of ET in the human esophagus, we measured contraction of isolated human esophageal muscularis mucosae strips caused by ET related peptides and binding of 125I-ET-1 to cell membranes prepared from the human esophageal muscularis mucosae. Autoradiography demonstrated specific binding of 125I-ET-1 to the muscularis mucosae and muscularis propria (muscularis externa) of the human esophagus. ET-1 caused tetrodotoxin and atropine-insensitive contraction of muscularis mucosae strips. In terms of the maximal tension of contraction, ET-1 and ET-2 were equal in efficacy. The relative potencies for ET related peptides to cause contraction were ET-1=ET-2>ET-3>sarafotoxin S6c (SX6c), an ETB receptor agonist. ET-1 caused contraction was mildly inhibited by BQ-123, an ETA receptor antagonist, and not by BQ-788, an ETB receptor antagonist. It was moderately inhibited by the combination of both antagonists, indicating synergistic inhibition. Furthermore, desensitization to SX6c with SX6c pretreatment failed to abolish the contractile response to ET-1, which was completely inhibited by BQ-123. These indicate the involvement of both ETA and ETB receptors in the contraction. Binding of 125I-ET-1 to cell membranes of the muscularis mucosae was saturable and specific. Analysis of dose–inhibition curves demonstrated the presence of ETA and ETB receptors. This study demonstrates that, the muscularis mucosae of the human esophagus, similar to that of the guinea pig esophagus, possesses both ETA and ETB receptors mediating muscle contraction.

Proteinase‐activated receptors 1and 2 mediate contraction of human oesophageal muscularis mucosae

Abstract  Proteinase‐activated receptors 1 and 2 mediate contraction of the human gallbladder. In the present study, we investigated effects mediated by proteinase‐activated receptors (PARs) in the human oesophagus by measuring contraction of muscularis mucosae strips isolated from the human oesophagus. Both PAR1 agonists (thrombin, SFLLRN‐NH2 and TFLLR‐NH2) and PAR2 agonists (trypsin, 2‐furoyl‐LIGRLO‐NH2 and SLIGKV‐NH2) caused concentration‐dependent contraction. In contrast, PAR1 and PAR2 control peptides did not cause contraction. The existence of PAR1 and PAR2 in the human oesophageal muscularis mucosae was confirmed by immunohistochemistry and reverse transcription‐polymerase chain reaction. On the other hand, PAR4 agonists, GYPGKF‐NH2, GYPGQV‐NH2 and AYPGKF‐NH2, did not cause contraction or relaxation in resting or carbachol‐contracted muscularis mucosae strips, suggesting that PAR4 is not involved in human oesophageal motility. The contractile responses to SFLLRN‐NH2 and trypsin in the human oesophagus were insensitive to atropine and tetrodotoxin, indicating that the contractile response was not neurally mediated. Taken together, these results demonstrate that PAR1 and PAR2 but not PAR4 mediate contraction in human oesophageal muscularis mucosae. PAR1 and PAR2 may influence human oesophageal motility.

Natriuretic peptides cause relaxation of human esophageal mucosal muscle

Natriuretic peptides have been demonstrated to cause relaxation of the human gallbladder muscle through interaction with natriuretic peptide receptor-B (NPR-B/NPR2). Effects of natriuretic peptides in the human esophageal muscle were unknown. To investigate the effects of natriuretic peptides in the human esophagus, we measured relaxation of muscularis mucosae strips isolated from the human esophagus caused by C-type natriuretic peptide (CNP), brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and des[Gln(18), Ser(19), Gly(20), Leu(21), Gly(22)]ANP(4-23) amide (cANP(4-23)), a selective natriuretic peptide receptor-C (NPR-C) agonist. In endothelin-1 or carbachol-contracted mucosal muscle strips, CNP caused moderate, sustained and concentration-dependent relaxation. BNP caused a very mild relaxation whereas ANP and cANP(4-23) did not cause any relaxation. CNP was much more potent than BNP and ANP in causing relaxation. These suggest the existence of NPR-B mediating relaxation. The CNP-induced relaxation was not affected by tetrodotoxin or atropine in endothelin-1-contracted esophageal strips and not by tetrodotoxin in carbachol-contracted strips, indicating a direct effect of CNP on the human esophageal muscularis mucosae. Taken together, these results demonstrate that natriuretic peptides cause relaxation of the muscularis mucosae of the human esophagus and suggest that the relaxation is through interaction with NPR-B. Natriuretic peptides may play an important role in the control of human esophageal motility.

Accidental pulmonary emboli noted by TEE during aortic valve replacement: a case report

Pulmonary embolism (PE) is difficult to diagnose clinically. In a patient who was scheduled for elective aortic valve replacement, several fresh emboli were recognized in the right atrium on transesophageal echocardiography (TEE). The PEs then disappeared on the echocardiographic image, with significant immediate hemodynamic changes noted by real-time monitors, such as tachycardia and increased pulmonary artery (PA) pressure. Pulmonary embolism was highly suspected. After cardiopulmonary bypass and aortic valve replacement, PA thromboembolectomy was performed successfully. The patient survived and was discharged from the hospital 17 days later without sequelae.

Successful Resection of a Mycotic Aneurysm of the Superior Mesenteric Artery

Aneurysm of the superior mesenteric artery is rare. More than 50% are mycotic. An aneurysm at this site ruptures easily and is difficult to manage. Here, we report a 49-year-old man with a mycotic aneurysm of the superior mesenteric artery, which was successfully resected, with revascularization from the infrarenal aorta using a retrograde vein graft.

Estrogen and G protein-coupled estrogen receptor agonist G-1 cause relaxation of human gallbladder

Objective: Estrogen interacts with a membrane receptor, G protein-coupled estrogen receptor (GPER). It was reported that 17β-estradiol was able to inhibit contraction of the human colon and cause relaxation of the guinea pig gallbladder, however, the involvement of GPER was not clarified. The aim of the present study was to investigate the effect of estrogen on human gallbladder motility and the possible role of GPER. Materials and Methods: Relaxation of human gallbladder strips were measured using isometric transducers. Expression of GPER was evaluated by reverse transcription polymerase chain reaction (PCR), realtime PCR, and immunohistochemistry. Results: In human gallbladder strips, 17β-estradiol and G-1 elicited marked and rapid relaxation, whereas tamoxifen produced mild concentration-dependent relaxation. The relative efficacies to cause relaxation were as follows: 17β-estradiol = G-1 > tamoxifen. The relaxant response of 17β-estradiol was not attenuated by tetrodotoxin or conotoxin GVIA. This implies that nerve stimulation was not involved in the 17β-estradiol-induced gallbladder relaxation. Analysis by reverse transcription PCR and real-time PCR showed that GPER was expressed in the human gallbladder. Further analysis by immunohisto-chemistry revealed that GPER was expressed in the gallbladder muscle. This suggests that 17β-estradiol relaxes the human gallbladder via GPER. Conclusion: These results demonstrate for the first time that 17β-estradiol and GPER agonist G-1 cause relaxation of the human gallbladder, probably through GPER. Estrogen might play an important role in the control of human gallbladder motility.

Prevalence, Risk Factors and Associated Cardiovascular Complications of Peripheral Arterial Disease in Type 2 Diabetic Patients in Eastern Taiwan

Objective: The purpose of this study was to evaluate the risk factors, including albuminuria, for peripheral arterial disease (PAD), and associated complications in patients with type 2 diabetes. Materials and Methods: All patients with type 2 diabetes 40 years old and over, were recruited consecutively from diabetic clinics at a medical center in eastern Taiwan. Information regarding each participants sociodemographic characteristics and medical history was gathered from the patients and their medical records. A clinical examination which included anthropometric measurements and a direct ophthalmoscope check-up was performed. After an overnight fast, serum lipids, uric acid, fasting plasma sugar, A1C and urinary albumin concentration were measured. The anklebrachial index (ABI) was calculated by Doppler examination in both legs. PAD was diagnosed if the ABI in one of the legs was less than 0.9. Results: A total of 309 patients were recruited. PAD was present in 38 of the 309 diabetic subjects studied (12.3%; 12.7% of the men and 11.9% of the women). Of all subjects with PAD, 92.1% had a history of hypertension, 15.8% had stroke, 13.2% had coronary heart disease, and 47.4% had albuminuria. For those who completed the direct ophthalmoscope examination, 41.9% of patients with PAD had diabetic retinopathy. In univariate analysis, the significant associative risk factors for PAD were age, tobacco smoking, history of hypertension/stroke, duration of diabetes, insulin therapy, usage of angiotension-converting enzyme inhibitors/angiotension-receptor blockers (ACEI/ARB) and albuminuria. Multiple logistic regression analysis identified age as the most significant risk factor for PAD. The higher the age of the patient, the greater the likelihood of PAD, with a 1.11-fold increase in risk incurred for every 1-year increment. Cigarette smoking was also a significant factor with smokers incurring a 4.77-fold higher risk than non-smokers. Individuals suffering from macroalbuminuria were more likely to have PAD compared to those without albuminuria. Other significant risk factors included insulin usage. Conclusions: The occurrence of PAD in type 2 diabetic patients is associated with the age of the patient, smoking, insulin usage and albuminuria. Incorporation of albuminuria assessment and a smokingcessation program are recommended in clinical practice.