Distribution,function and physiological role of melatonin in the lower gut

Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

EFFECTS OF GLIBENCLAMIDE, GLIMEPIRIDE, AND GLICLAZIDE ON ISCHEMIC PRECONDITIONING IN RAT HEART

Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP) of rat ventricular myocytes. Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: (1) control group, (2) IPC group, (3) IPC+glibenclamide (GLB, 10 μmol/L) group, (4) IPC+glimepiride (GLM, 10 μmol/L) group, (5) IPC+gliclazide (GLC, 50 μmol/L) group. IPC was defined as 3 cycles of 5-minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded. And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1 μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition. Results The infarct sizes of rat hearts in IPC (23.7%±1.3%), IPC+GLM (24.6%±1.0%), and IPC+GLC (33.1%±1.3%) groups were all significantly smaller than that in control group (43.3%±1.8%; P<0.01, n=6). The infarct size of rat hearts in IPC+GLB group (40.4%±1.4%) was significantly larger than that in IPC group (P<0.01, n=6). Under simulated ischemic condition, GLB (10 μmol/L) decreased IKATP from 20.65±7.80 to 9.09±0.10 pA/pF (P<0.01, n=6), GLM (1 μmol/L) did not significantly inhibit IKATP (n=6), and GLC (1 μmol/L) decreased IKATP from 16.73±0.97 to 11.18±3.56 pA/pF(P<0.05, n=6). Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.

Biomechanical evaluation of lumbosacral reconstruction after subtotal sacrectomy: A three-dimensional finite element analysis

Objective： The aim of this study was to investigate the biomechanical property of lumbosacral reconstruction after subtotal sacrectomy. Methods： Three three-dimensional finite element models of lumbosacral region were established： （1） An intact model （INT）; （2） A defective model （DEF） on which subtotal sacrectomy was performed cephalad to the $1 foramina; （3） A reconstructed model （REC）. These models were validated by compared with literature. Upright posture was stimulated under a compression load of 925N. A finite element analysis was performed to account for the displacement and stress on the models. The REC model was calculated twice, with the material property of reconstruction instrument set as titanium and stainless steel, respectively. Results： The displacements of anchor point on the L3 vertebrae in INT, DEF and REC model were 6.63 mm, 10.62 mm, 4.29 mm （titanium） and 3.86 mm （stainless steel）, respectively. The stress distribution of the instrument in REC model showed excessively concentration on caudal spinal rod, which may cause rod failure between spine and ilia. The maximum von Mise stress of stainless steel instrument was higher than that of titanium instruments （992 MPa vs 655 MPa）, and the value of stress of anchor point around sacroiliac joint in REC model were 26.4 MPa with titanium instruments and 23.9 MPa with stainless steel instruments. Conclusion： Lumbosacral reconstruction can significantly increase the stiffness of spino-pelvis of the patient who underwent subtotal sacrectomy. However, the rod between L5 and ilia is the weakest region of all the instruments. It is suggested that the bending of rod should be conducted carefully and smoothly to avoid significant stress concentration so as to reduce the risk of rod failure. And stainless steel instrument has higher maximum stress and significantly greater stress shielding effect than titanium instrument, which means stainless steel instruments are of higher risk of rod failure and less favorable for lumboiliac arthrodesis than titanium instruments.

Surgical strategy for presacral tumors： analysis of 33 cases

Background Presacral tumors are highly infrequent tumors located in the space known as presacral or retrorectal space. Although there have been substantial improvements in the prognosis of patients with malignant presacral tumors, the development of newer surgical strategy is likely to further improve the oncologic outcomes of malignant presacral tumors. The aim of this article was to report our experience in 33 cases, and to review the surgical strategy, pathological features and the prevention of complications from our experience. Methods A retrospective analysis was conducted on 33 cases （20 male and 13 female） with presacral tumors surgically treated in our hospital between January 1998 and April 2009. The surgical approaches included trans-abdominal in 10 cases （30%）, trans-sacral in 18 cases （55%） and combined abdominal-sacral in 5 cases （15%）. All patients got followed up （14-123 months, mean of 45.1 months）. At last, the general information, clinical symptoms, histodiagnosis, surgical types and postoperative complications of all cases in our series were assessed. Results Ages of 33 patients ranged from 18 to 71 years, with an average of 48.5 years. Pathological findings： 6 epidermoid cysts, 5 teratomas, 3 leiomyomas, 9 neurofibromas, 5 neurilemmomas, 1 enterogenous cyst, 1 liposarcoma, 1 leiomyosarcoma, 1 angiosarcoma, and 1 neurofibrosarcoma. All tumors were excised with no perioperative death. A colostomy was taken in one case with angiosarcoma involving the rectum because of the intraoperative injury of the rectum. Blood loss during surgery was 400-11 000 ml （mean of 2400 ml）. Four （12%） cases had local recurrence during follow-up： 2 because of inadequate drainage after dermoidectomy, both of them were cured by surgical resection and drainage; recurrence occurred in a case of teratoma in 18 months after surgery, cured by a trans-sacral excision; local recurrence and lung metastasis occurred simultaneously in a case of angiosarcoma in 6 months postoperatively and the patient died one month later of respiratory failure. Conclusions The main treatment of most presacral tumors is surgical resection. Selection of surgical approach is very important for complete resection of the presacral tumors. The location, size and peculiarities of tumors, conditions of the skin and soft tissues and the patients＇ somatotype are all determinative factors. Multidisciplinary cooperation is also very necessarv.

Prognostic value of Her-2/neu and clinicopathologic factors for evaluating progression and disease-specific death in Chinese men with prostate cancer

Background Her-2/neu gene overexpression has been found in several malignancies, and is associated with poor prognosis; while its role in the tumorigenesis and progression of prostate cancer （PCa） is still controversial. This study aimed to evaluate the prognostic value of Her-2/neu protein expression and clinicopathologic factors in antiandrogen-treated Chinese men with PCa for disease progression and PCa-specific death. Methods Her-2/neu protein expression was determined using immunohistochemistry （IHC） in specimens collected from 124 prostate biopsies and transurethral resection of prostate （TURP） from seven prostate cancer patients. Results Her-2/neu protein expression was 0, 1＋, 2＋, and 3＋ in 40 （30.5%）, 8 （6.1%）, 67 （51.1%）, and 16 （12.2%） cases respectively. Her-2/neu protein expression showed significant correlation as judged by Gleason score （P=0.049）, clinical tumor-node-metastases （cTNM） stage （P=0.018） and disease progression （P=0.001）, but did not correlate with prostate-specific antigen （PSA） （P=0.126） or PCa-specific death （P=0.585）. PSA （P=0.001）, Gleason score （P=0.017）, cTNM （P=-0.000） and Her-2/neu protein expression （P=0.001） had prognostic value for evaluating the progression of PCa in univariate analysis. In Kaplan-Meier plots, both Gleason score （P=0.035） and cTNM （P=0.013） correlated with PCa-specific death. In multivariate analysis, only cTNM was significant for both disease progression （P=0.001） and PCa-specific death （P=0.031）. Conclusions Her-2/neu protein expression is significantly correlated with Gleason score, cTNM and disease progression, although it is not an independent predictor of disease progression and PCa-specific death, cTNM staging serves as an independent prognostic factor for disease progression and PCa-specific death.

Multi-link Vision and MiniVision stent registry in Asian patients with coronary artery disease:a prospective,multi-center study

Background Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries. To maintain a very satisfactory radio-opacity using the stents, Guidant of the USA has designed a new type of bare metal stents （BMS）-Multi-link （ML） Vision / ML MiniVision stents. The clinical outcomes of Asian patients with coronary artery disease （CAD） after implanting the Multi-link Vision or MiniVision stent were investigated in this study. Methods An observational, prospective, multi-center, non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS- ML Vision / ML MiniVision stents. The primary end point of the registry was clinical target lesion revascularization （TLR） at a 6-month follow-up. The major secondary end points included the rate of major adverse cardiac events （MACE） and serious adverse events （SAE） in hospital and at 6 months; and the rate of clinical TLR as a function of the type of angina. A total of 429 Asian people with 449 lesions from 14 centers were selected for this study, The average reference diameter of the lesions was （3.0±0.5） mm, and the mean length was （15.7±5.0） mm. Results The successful rate of the procedure was 99.3%. Twenty-five percent of the lesions were treated by direct stenting without pre-dilation. Eighty-six percent of the lesions were implanted with ML Vision stent. After the 6-month follow-up, the rate of clinical TLR was 1.4%. The MACE, SAE and target vessel revascularization （TVR） were 6.8%, 3.5% and 1.4% respectively. Conclusion The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD.