可逆性胆硷酯酶抑制剂二甲氨基甲酸-5-二氢吲哚酯的合成

为了深入研究催醒宁类化合物的结构与抑酶活性的关系,设计合成了-系列1-,3-或5-位不同取代的二氢吲哚类衍生物(中间体和终产物共24个新化合物)。中间体1,3-二甲基-5-烷氧基-2-二氢吲哚酮(A)的C₃烷化。采用相转移催化方法进行;反应中还分离到三个副产物(Ⅶ～Ⅸ)。初筛结果表明:这些化合物大多有较强的抑酶活性;1,3-或5-位取代基的改变均明显影响其活性。     

Prevalence of menstrual pain in relation to the reproductive life history of women from the Mayan rural community

BACKGROUND: The prevalence of menstrual pain in Western societies is relatively high and has been shown to be related to many factors (e.g. age, menarche age, parity, menstrual cycle regularity, cigarette smoking, dietary habits). However, less data are available for traditional societies, within which there are, presumably, not as many potentially disturbing factors that could influence menstrual symptoms as in Western societies. AIM: The study seeks to determine the prevalence of dysmenorrhoea, and the factors related to menstrual pains in women with natural fertility (i.e. without hormonal forms of contraception). SUBJECTS AND METHODS: 177 non-smoking women between 18 and 45 years of age living in one Mayan village (Yaxcaba, Yucatan, Mexico) were the subjects of this study. The method of logistic regression was used with the dichotomous dependent variable being the presence or absence of menstrual pain together with such independent variables as age, age at menarche, number of pregnancies, age when giving birth to the first child, the weight at interview and BMI. RESULTS: The general prevalence of the menstrual pains was 28%. There was only one variable influencing dysmenorrhoea, namely the age at which women give birth to their first children. Those mothers who gave birth to their first child at an earlier age (at mean age of 19.4 vs 21.1 years) had a lower prevalence of dysmenorrhoea. CONCLUSION: In the studied traditional society the main factor related to menstrual pain was the age at which woman first gave birth. It is hypothesized that an earlier start to reproductive life in some way decreases the sensitivity of the uterus to prostaglandins.     

Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish.

Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17-21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp-4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve.     

A somatostatin analogue decreases embryonic loss following superovulation in rats by normalizing insulin-like growth factor-I action in the uterus

This study was designed to determine whether the somatostatin analogue, octreotide, could prevent embryonic loss by normalizing increased uterine insulin-like growth factor-I (IGF-I) action related to hyperoestrogenaemia following superovulation. Superovulated immature and oestradiol-17beta-treated adult rats were infused with 100 or 300 microg/ml of octreotide respectively, or injected daily with 1 or 10 microg of octreotide from day 1 to day 3 of pregnancy. On day 3, embryos were collected from the oviducts and uteri. Uterine luminal fluid was subjected to embryo culture. The amounts of uterine IGF-I and IGF binding proteins (IGFBP) were determined by radioimmunoassay and ligand binding assay respectively. Octreotide infusion normalized uterine IGF-I action following superovulatory and oestradiol-17beta treatment, by reducing IGF-I concentrations and increasing IGFBP concentrations. Octreotide infusion increased the number of normal embryos by 2.7-fold and 1.7-fold in superovulated and oestradiol-17beta- treated rats respectively, and reversed the detrimental effects of uterine luminal fluid on embryonic development caused by superovulatory and oestradiol-17beta treatment. Daily injections with octreotide had similar but reduced effects in all parameters examined in both treatment groups. In conclusion, octreotide may reduce embryonic loss, at least in part, by normalizing IGF-I action following superovulation.      

Complications of laparoscopy and thoracoscopy

Laparoscopy was first performed at the turn of the century, but it was not until the introduction of laparoscopic cholecystectomy that the procedure became widely adopted by general surgeons. Since then, traditional open procedures, including cholecystectomy, exploratory laparotomy, colectomy, hernia repair, and appendectomy, are being widely performed laparoscopically. The advantages of laparoscopic surgery, including less postoperative pain due to smaller surgical incisions, shorter hospital stay, quicker return to preoperative activity, and superior cosmesis, resulted in widespread popularity with both surgeons and patients. In certain situations, the traditional method may be superior to the laparoscopic approach, as may be the case with laparoscopic hernia repair. It is difficult to justify converting a local, extraperitoneal, 45-minute, outpatient inguinal hernia repair in a virgin groin into a general anesthetic, transperitoneal, 2-hour plus, possibly inpatient laparoscopic procedure with the implantation of mesh. However, data may indicate that this operation does indeed have benefits. We must, therefore, carefully study such new operations. With the advent of a new surgical procedure, both surgeons and anesthesiologists must be familiar with the various complications unique to this technique. If recognized early, potentially life-threatening complications, including gas embolization and tension pneumothorax, can be corrected.     

A prospective trial of short‐fractionation radiotherapy for the palliation of liver metastases

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty‐eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty‐two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high‐dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53?66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well‐tolerated treatment achieves useful palliation.     

Epstein–Barr virus DNA load in peripheral blood mononuclear cells and whole blood from pediatric transplant recipients

B. Kasztelewicz, I. Jankowska, J. Paw?owska, J. Teisseyre, R. Grenda, M. Pronicki, K. Dzier?anowska‐Fangrat. Epstein–Barr virus DNA load in peripheral blood mononuclear cells and whole blood from pediatric transplant recipients.
Transpl Infect Dis 2011: 13: 471–479. All rights reserved Abstract: Monitoring of circulating Epstein–Barr virus (EBV) DNA in pediatric transplant patients has been shown to be useful in post‐transplant patient management. It still remains unclear which blood sample type is more suitable, and how EBV DNA levels in whole blood (WB) correlate with those in peripheral blood mononuclear cells (PBMCs). The aim of this study was to compare EBV DNA load in WB and PBMCs of pediatric transplant recipients. After liver, kidney, or combined liver–kidney transplantation, 172 matched WB and PBMCs samples were collected from 84 children (130 samples from 42 patients consisted of multiple collections). The EBV DNA level in PBMCs was determined by home‐made real‐time polymerase chain reaction using TaqMan chemistry. In parallel, the viral load (VL) in WB was measured by a commercial LightCycler EBV Quant Kit. The EBV DNA levels and dynamics of VL changes were assessed and compared between WB and PBMCs. The overall correlation between EBV DNA level in PBMCs and WB was statistically significant and high, r²=0.87 (P<0.001). However, the sensitivity of EBV detection was lower in WB (93.9%). Longitudinal analysis of EBV DNA load dynamics in PBMCs and WB indicated that EBV DNA load fluctuations were larger in WB, but the trend of decreases and increases, with minor exceptions, was similar in both sample types. The high correlation of EBV DNA levels, as well as the similar dynamics of EBV DNA changes in both sample types, make WB a good alternative to EBV DNA monitoring in PBMCs of pediatric transplant recipients. However, the subtle increase of the VL may be detected earlier in PBMCs.