Somatostatin sst5 inhibition of receptor mediated regeneration of rat aortic vascular smooth muscle cells

1. The aim of the present study was to determine the effect of somatostatin (SRIF) on mitogen-induced regeneration of rat aortic vascular smooth muscle cells (VSMC) and for comparison Chinese hamster ovary (CHO)-K1 cells expressing human recombinant sst₅ receptors (CHOsst₅), following partial denudation of a confluent cell monolayer. Regeneration was assessed by measuring areas of recovery into the denuded area and by counting total cell numbers.
2. In VSMC, SRIF (0.1 nM–1 μM) had no effect on the basal levels of regeneration but caused a concentration-dependent inhibition (pIC₅₀ 8.0–8.6) of the stimulated regeneration induced by sub-maximal concentrations of basic fibroblast growth factor (bFGF, 10 ng ml⁻¹), platelet-derived growth factor-BB (PDGF, 5 ng ml⁻¹) or endothelin-1 (ET-1, 100 nM). SRIF (pIC₅₀ 8.8) also inhibited bFGF-induced regeneration of CHOsst₅ cells.
3. In VSMC, the inhibitory action of SRIF on the regeneration induced by bFGF (10 ng ml⁻¹) was due to an anti-proliferative effect, rather than an effect on cell migration, as SRIF (0.1 nM–1 μM) abolished bFGF-induced increases in total cell numbers. The bFGF-induced increase in cell numbers was also abolished by actinomycin D (0.1 μg ml⁻¹).
4. The sst₅ receptor-selective agonist, L-362,855 (pIC₅₀ 10.5), was about 100 times more potent than SRIF at inhibiting bFGF-induced regeneration of both VSMC and CHOsst₅ cells whilst the sst₂ receptor-selective agonist, BIM-23027 (pIC₅₀ 6.8), was approximately 20 times weaker than SRIF.
5. The sst₅ receptor antagonist, BIM-23056 (100 nM), antagonized SRIF-induced inhibition of bFGF-induced regeneration in both VSMC and CHOsst₅ cells (estimated pK_B values 8.8 and 8.3, respectively).
6. SRIF-induced inhibition of bFGF-induced regeneration of VSMC and CHOsst₅ cells was abolished by pretreating cells with pertussis toxin (100 ng ml⁻¹) for 20 h.
7. These findings suggest that SRIF-induced inhibition of the proliferation of rat aortic VSMC is mediated via activation of receptors which are similar to human sst₅ receptors. Furthermore this inhibitory effect is transduced via pertussis toxin-sensitive G_i/G_o proteins.

     

Rest and treadmill exercise first-pass radionuclide ventriculography: Validation of left ventricular ejection fraction measurements

Background

To assess the accuracy of rest and treadmill exercise first-pass radionuclide ventriculographic measurements of left ventricular ejection fraction (LVEF), 40 patients underwent treadmill exercise first-pass and bicycle exercise equilibrium radionuclide ventriculography. To determine the frequency of technically adequate treadmill exercise first-pass studies, an additional 128 consecutive patients undergoing treadmill exercise first-pass procedures during stress^99mTc-labeled sestamibi myocardial perfusion studies were assessed.

Methods and Results

The treadmill exercise first-pass procedure used a multicrystal camera and an²⁴¹Am point source to allow for correction of patient motion. Excellent correlations were observed between resting first-pass and resting equilibrium LVEF (r=0.91; standard error of the estimate=5.6). A high correlation was also observed between treadmill exercise first-pass and bicycle equilibrium exercise LVEF measurements (r=0.85, standard error of the estimate=7.6). Treadmill first-pass LVEF systematically underestimated the bicycle equilibrium LVEF. Intraobserver agreement for rest and exercise first-pass LVEF was high (r values of 0.98 and 0.94, respectively). Of the 168 consecutive treadmill exercise first-pass studies evaluated for technical adequacy, 21 (12.5%) were deemed technically inadequate, with most of the sources of error being avoidable. The frequency of technically adequate studies was as high (87%) in high levels of exercise (Bruce stages 3 and 4) as in lower levels (88%). The findings of this study validate the first-pass treadmill exercise LVEF measurement.

Conclusion

This procedure now provides the option for combining the information of peak treadmill exercise LVEF with measurements of exercise myocardial perfusion from the same injection of radioactivity.     

Vagal Nerve Monitoring during Parapharyngeal Space Tumor Removal

The vagus nerve innervates the intrinsic and extrinsic laryngeal musculature as well as the complex pharyngeal plexus. Acute paralysis of this nerve results in dysfunctional speech, deglutition, and airway protection. These untoward effects, which lead to additional infectious and aerodigestive complications, may arise following manipulation of the vagus nerve during the surgical removal of a variety of neoplasms found in the parapharyngeal space.The vagal nerve has been intraoperatively monitored in an effort to maintain its anatomic and functional integrity. Bipolar hook-wire electrodes are introduced transcutaneously through the cricothyroid membrane and are guided into the vocalis muscle by an assistant performing direct laryngoscopy. Continuous, real-time monitoring of the vagal nerve is provided by audio and visual feedback to the operating surgeon. Potentially injurious stretching, heating, and compression of the nerve are easily detected, and monopolar stimulation of the nerve is used to map the nerve's course through the tumor bed.This presentation outlines our technique for vagal nerve monitoring in patients with tumors of the parapharyngeal space and intact preoperative vocal cord mobility. Selected cases are presented and illustrated through intraoperative and postoperative videotapes.     

Retrovirus-mediated gene-transfer of tnf receptor for treatment of cancer

Tumor necrosis factor-alpha receptor cDNA (TNFR-1 or TNFR-2) was inserted into a retrovirus derived vector. Recombinant vector was transfected into packaging cell line. The transfectants producing high titer of virus containing TNFR-1 or TNFR-2 cDNA were obtained. Human stomach cancer cells that poorly expressed TNFR-1 or TNFR-2 were infected with this virus as an in vitro model experiment of gene therapy. The stomach cancer cells that were infected with recombinant virus expressed TNFR-1 or TNFR-2 and were effectively killed by recombinant TNF.     

Comparison of survival among patients with breast cancer treated at First Teaching Hospital,Changchun, China,and Saint-Sacrement hospital,Quebec, Canada

The aim of this study was to compare the survival of 116 patients with breast cancer initially treated at the First Teaching Hospital (FTH) of Norman Bethune University of Medical Sciences located in Changchun, China, from 1986 to 1991 with the survival of 886 patients seen in the “Hipital du Saint-Sacrement” (HSS) located in Quebec City, Canada, from 1987 to 1992. The clinical data were collected from the hospital records at FTH. The vital status for Chinese patients was obtained from letters of follow-up or the records of local police offices. The list of patients treated at HSS and the data for each woman were extracted from computerized data banks. The major variables studied included age at diagnosis, tumor size at pathology (cm), number of lymph nodes involved, breast surgery and adjuvant treatments of breast cancer (chemotherapy, radiotherapy, immuno-therapy). Age at diagnosis was substantially lower among patients with breast cancer seen at FTH compared to those treated at HSS (x) ₁ ² =60.95,P<0.0001). The average age at diagnosis for Chinese women was about 10 years less than that for Canadian women. Patients in the two hospitals differed with respect to tumor size at pathology (x ₂ ² =6.67,P=0.036). The proportion of patients with tumor size larger than 2.0 cm was larger at FTH (48.3%) than at HSS (41.1%). The mean tumor size at pathology was 3.0 cm (standard deviation =2.1 cm) for patients treated at FTH, but 2.6 cm (standard deviation=1.8 cm) for women treated at HSS (P=0.07). The proportion of women with lymph node involvement was greater at FTH (61.1 % than that at HSS (37.3%) (x ₁ ² =16.51,P<0.0001). Surgical treatment of breast cancer varied considerably. In Changchun, radical mastectomy was frequent for any stage of breast cancer patients, but partial mastectomy was never performed. The situation was reversed in Quebec. The five year observed survival was 74.2% (standard error, 0.05) among breast cancer patients seen at FTH compared to 76.0% (standard error, 0.02) among women treated at HSS. After adjustments of confounding factors, there were no significant difference in five year observed survival between the patients treated at the two hospitals (P=0.42).     

职业人群不健康行为生活方式与高尿酸血症的关系及高血压、血脂异常的效应修饰作用

目的 探索不健康行为生活方式与高尿酸血症的关系,以及高血压、血脂异常的效应修饰作用,为预防高尿酸血症提供理论依据。方法 采用横断面调查研究设计,基于2021年10-12月来自四川省、贵州省28个地级市和重庆市33个区（县）中国铁路成都局集团有限公司的西南职业人群队列基线数据,通过问卷调查、体格测量及实验室生化检测收集研究对象的人口学特征、行为生活方式、慢性非传染性疾病患病情况。不健康行为生活方式得分根据吸烟、饮酒、膳食模式、体力活动和低体重/超重状况进行评分,分值越高不健康行为生活方式越多。采用多因素logistic回归模型分析不健康行为生活方式评分、吸烟状况、饮酒状况等与高尿酸血症的关系,采用分层分析探索高血压等疾病对不健康行为生活方式与高尿酸血症之间关系的修饰效应。结果 共纳入11 748名研究对象,高尿酸血症患病率为34.4%。多因素logistic回归分析显示,现在吸/既往吸烟、现在饮/既往饮酒及BMI异常是高尿酸血症患病的危险因素,不健康行为生活方式对高尿酸血症患病风险呈现累积效应,随着得分的升高,高尿酸血症患病风险升高,OR值由1.64（95%CI：1.34~2.00）上升至2.89（95%CI：2.39~3.50）。分层分析结果显示,在高血压及血脂异常人群中,不健康行为生活方式对高尿酸血症患病风险影响更大。结论 多种不健康行为生活方式的共存会升高高尿酸血症患病风险,这一效应在高血压、血脂异常人群中更明显。及时纠正不健康行为生活方式,并控制高血压和血脂异常,降低患高尿酸血症的风险。     

上海市50岁及以上人群维生素D水平与握力的关联研究

目的 探讨上海市≥50岁人群维生素D水平与握力的关系。方法 数据来源于WHO全球老龄化与成人健康研究我国上海市2018-2019年数据,采用logistic回归模型分析维生素D水平与握力的关系,进一步按照性别、年龄及乳制品摄入情况进行分层;采用限制性立方样条曲线绘制维生素D水平与低握力的剂量-反应曲线。结果 共4 391人纳入研究,其中男性2 054人（46.8%）;年龄（67.02±8.81）岁;低握力1 421人（32.4%）;维生素D不足及缺乏分别为1 533人（34.9%）和401人（9.1%）。在调整相关混杂因素后,logistic回归分析结果显示,维生素D缺乏的人群发生低握力的风险更高（OR=1.41,95%CI：1.09~1.83）;在男性中,调整相关混杂因素后,维生素D缺乏与低握力发生风险呈显著正相关（OR=1.67,95%CI：1.12~2.50）,而女性中两者之间无关联（OR=1.30,95%CI：0.97~1.74）;在60~69岁及≥80岁年龄组中,调整相关混杂因素后,维生素D缺乏与低握力发生风险呈显著正相关（OR=1.57,95%CI：1.05~2.35;OR=2.40,95%CI：1.08~5.31）,在乳制品摄入<250 ml/d的人群中,调整相关混杂因素后,二者之间呈显著正相关（OR=1.57,95%CI：1.17~2.09）,而在乳制品摄入≥250 ml/d的人群中无明显关联。限制性立方条样图显示,低握力的发生风险可能随维生素D含量的上升而降低,但差异无统计学意义（P>0.05）。结论 维生素D水平与握力存在一定的关系,维生素D缺乏人群出现低握力的风险更高。     

矽肺相关蛋白的纯化,鉴定及其促成纤维细胞增殖作用

目的分离、鉴定与矽肺发生、发展过程相关的几种蛋白质,并测定其促成纤维细胞增殖的活性。方法采用高压液相色谱技术包括凝胶过滤柱层析、离子交换柱层析、反相Ｃ４高压液相色谱柱层析,分别对矽肺大鼠肺泡灌洗液（ＢＡＬＦ）、肺泡巨噬细胞冻融物（ＡＭＥ）及其条件培养液（ＡＭＣＭ）进行分离纯化,并通过Ｎ末端氨基酸序列的测定来鉴定这些蛋白质。结果（１）染尘２１天后,矽肺大鼠ＢＡＬＦ中白蛋白含量明显升高;（２）从ＢＡＬＦ、ＡＭＥ和ＡＭＣＭ中除纯化到相对分子质量为１５４００的溶菌酶外（其刺激成纤维细胞增殖的活性为１４０％）,还纯化到一种新的具有明显促成纤维细胞增殖的细胞因子（Ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｐｒｏｍｏｔｉｎｇｆａｃｔｏｒ,ＦＧＰＦ）,其最适作用浓度为２．０～６．０μｇ／ｍｌ。结论巨噬细胞分泌的ＦＧＰＦ和溶菌酶在矽肺纤维化过程中可能有重要作用。     

几种改进的漂浮颗粒剂灭中华按蚊和致倦库蚊的效果

目的：比较几种改进的漂浮颗粒剂灭中华按蚊和致倦库蚊幼虫的效果。方法：现场试验。结果：室内生物测定,Ｂ．ｔ．ｓ－１８７漂浮颗粒剂（荷叶型）ＬＤ５０为０．４０８７μｇ／ｍｌ,Ｂａｃｔｉｍｏｓ颗粒剂（荷叶型）ＬＤ５０为０．９３４４μｇ／ｍｌ,Ｂ．ｓ－Ｃ３－４１漂浮颗粒剂（荷叶型）ＬＤ５０为０．０５９９μｇ／ｍｌ。稻田灭中华按蚊幼虫的效果显示：两种Ｂ．ｔ．ｓ漂浮颗粒剂（荷叶型）０．８１ｇ／ｍ２剂量时,２４ｈ灭蚊效果均可达１００％。１８７漂浮颗粒剂持效可达１１ｄ,Ｂａｃｔｉｍｏｓ漂浮颗粒剂持效为８ｄ。１８７颗粒剂和Ｂ．ｓ－Ｃ３－４１颗粒剂现场灭致倦库蚊的效果显示：在０．６８ｇ／ｍ２剂量时,２４ｈ蚊幼密度下降率分别为１００％和９９．１％,持效分别为９ｄ和８ｄ。结论：采用荷叶粉为主要载体,在自然界中易于分解,不造成污染,而且灭蚊即效和持效均较好。