多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT) and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca^2 was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC5o=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP) kinase inhibitor (PD98059; IC5o=3 ktmol/L). The effect was also inhibited by a specific tyrosine light chain kinase(TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca^2 , COX, and MAP kinase pathways.     

Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome

OBJECTIVE: The emerging role of transforming growth factor beta in hypertension, kidney disease, and trophoblast differentiation promoted our interest in evaluating the clinical value of assaying maternal serum TGF-beta2 levels in pregnancies complicated by preeclampsia and eclampsia. We wished to determine these levels in relation to the severity of the disease, the degree of renal involvement, and fetal outcome. METHODS: A prospective study was carried out in 50 pregnant patients with preeclampsia (PE) and eclampsia and these women were compared to 20 pregnant normotensive controls. Preeclamptic patients were subdivided into 20 cases of mild PE, 20 cases of severe PE, and 10 cases of eclampsia. Maternal serum levels of TGF-beta2 were determined in all cases by enzyme immunoassay. Maternal serum creatinine and uric acid were measured, together with an assessment of fetal well being, using the Biophysical Profile Score. RESULTS: Maternal serum TGF-beta2 levels were significantly increased in cases of severe preeclampsia and eclampsia compared to controls. This increase was positively correlated with elevated levels of serum creatinine and uric acid, as well as poor biophysical profile scores (BPS), and low birth weight (LBW). CONCLUSION: Measurement of maternal serum TGF-beta2 levels in preeclampsia may be a useful biomarker for the assessment of the severity of disease and fetal outcome in PE.     

Possible horizontal transfer of the vanB2 gene among genetically diverse strains of vancomycin-resistant Enterococcus faecium in a Korean hospital

A total of 25 isolates of vanB-containing Enterococcus faecium were recovered from patients in a single Korean hospital over a 20-month period. There were two distinct vanB2 patterns among the 11 pulsed-field gel electrophoresis types; 17 contained the prototype vanB2 and 8 contained a novel vanB2 with a 177-bp deletion in vanY(B). Both vanB2 genes were transmissible in vitro at a mean frequency of 1.1 x 10(-8) transconjugants/donor. These results suggest the horizontal spread of vanB2 is occurring among genetically diverse strains of E. faecium in Korean hospitals.     

Resolution of gastritis induced by Helicobacter pylori 4-5 weeks after successful eradication of infection using a triple therapy regimen of pantoprazole, amoxycillin and clarithromycin for one week.

This open-label study was designed to determine the extent of histological resolution of gastritis induced by Helicobacter pylori infection 4-5 weeks after successful eradication of the infection. Eradication was achieved using a triple therapy regimen consisting of a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg taken for 1 week only. No other medications were given thereafter. Four biopsies were processed for histological examination of each patient, two from the antral and two from the corporeal mucosa, first at the start of the study and then again 4 weeks after cessation of the medication trial. Scoring for H. pylori colonization and the severity of gastritis was determined for each patient according to the Sydney system. 53 of 57 patients in this study had their H. pylori infection successfully eradicated by the regimen mentioned and could be histologically evaluated. According to the severity of gastritis in the antral mucosa, patients were studied in 3 groups: mild, moderate and severe gastritis. 17 of 19 cases with mild gastritis showed complete resolution of the inflammation, with residual inflammatory changes persisting in 2 cases only. 22 of the 26 cases with moderate gastritis showed almost complete recovery except for minor residual inflammatory changes as judged by irregularity of intracytoplasmic mucine storage. Persistent residual inflammatory changes in the lamina propria were detected in 4 cases. Of the 8 cases with severe gastritis 5 showed subsidence of the inflammatory changes, but the mucosa in these cases revealed some scarring, distortion of the glandular epithelium and atrophy. In 3 cases residual inflammation persisted. CONCLUSION: One-week therapy with a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1,000 mg, used to eradicate H. pylori causing active inflammation of the gastric mucosa, has led to subsidence of the acute inflammatory changes in all the cases with residual inflammation persisting in 17%. Severe gastritis may cause irreparable damage to the gastric mucosa. The density of H. pylori colonization does not appear to be related to the severity of gastritis, nor to the successful eradication achieved.     

Feasibility of using computer simulation to predict the postoperative outcome of the minimally invasive Nuss procedure: Simulation prediction vs. postoperative clinical observation

The Nuss procedure is the most minimally invasive and commonly used surgical correction for pectus excavatum (PE) by using a prebent pectus bar to elevate the deformed chest wall. However, there are some complications associated with this procedure such as postoperative pain as well as surgical uncertainties because of human judgment. It is therefore important to understand the biomechanical effect of the pectus bar on PE thoraces undergoing an operation to alleviate the postoperative pain as well as to improve surgical outcome. The current study incorporated the finite element method (FEM) to simulate the entire Nuss procedure including the flipping process of the pectus bar on a preoperative PE patient-specific thorax model, in conjunction with comparison against the postoperative CT scans. The mid-sagittal sternovertebral elevation was found to be within 5.32?mm, whereas the transverse sternal deviations ranged from 1.59 to 3.02?mm. The average discrepancy between the predicted contour and postoperative CT contour was approximately 3%. On a different note, the stress and strain distributions largely concurred with reported findings. High bilateral stress was seen to occur at the back of ribs near the vertebral column, and particularly over the second to fifth ribs, whereas the greatest strain was found to be confined to the regions of costal cartilages. It is evident that the FEM is a feasible and robust approach in predicting the outcome of the mechanical surgical procedure. This contributes to the future development of a predictive tool incorporated in surgical planning to enhance surgical management of PE.     

Chemo-radiotherapy: an alternative to surgery for squamous cell carcinoma of the rectum – report of six patients and literature review

Purpose  Since 1943 [ 1 ], only 45 patients of squamous cancer of the rectum have been reported in the published reports and the largest series to date consists of 12 patients. Reports suggest that the primary treatment is surgical resection but, in the light of nonsurgical advances in the treatment of anal squamous cell carcinoma (SCC), we present a review of the literature and report six patients treated by chemoradiation therapy (CRT).
Method  A literature search was undertaken using the keywords squamous cell, epidermoid, basaloid and cloacagenic and cancer of rectum and colon to provide evidence for this discussion from studies of surgery, radiation therapy and CRT in rectal SCC. A prospective database of the Mount Vernon Cancer Centre, UK was searched from 1995 to 2005 for patients diagnosed with pure SCC of the rectum.
Results  Six patients with histologically confirmed primary SCC of the rectum were treated with primary combination chemo-radiotherapy according to protocols used for SCC of the anal canal over a 15-year period. Surgery was avoided in four, and they remain disease-free on follow-up.
Conclusions  Primary CRT, as currently utilized in anal cancer, can be extended to primary SCC of the rectum.