Polykystose rénale autosomique dominante : le traitement est-il pour demain ?

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent Mendelian inherited disorder. It covers 6.1% of incident ESRD patients in France in 2011. Long left untreated, this disease will soon benefit from targeted therapies currently under evaluation. Several molecules have already reached the stage of clinical trials: the evaluation of mTOR inhibitors yielded deceiving results and, more recently, 2 different molecules demonstrated a slight impact on the progression of total kidney volume (TKV): tolvaptan, vasopressin receptor-V2 inhibitor and somatostatin analogues; both of these molecules acting throughout the decrease of intracellular AMPc. The purpose of this review is to briefly describe the signaling pathways involved, then to present both the published and ongoing clinical trials and the promising molecules evaluated in murine models.     

Evaluation of efficacy,biodistribution and safety of antibiotic-free plasmid encoding somatostatin genes delivered by attenuated Salmonella enterica serovar Choleraesuis

We describe here a balanced-lethal system using an Asd⁺ expression plasmid pVGS/2SS-asd encoding two copies of somatostatin (SS) genes carried by Δasd/Δcrp double mutant Salmonella enterica serovar Choleraesuis (named C501). The advantage of this novel system is the use of asd (aspartate-semialdehyde dehydrogenase) gene as selection marker to replace the antibiotic resistance markers, thus eliminating the industrial cultivation and environmental problems. We then evaluated the efficacy, biodistribution and safety of antibiotic-free plasmid delivered by strains C501. Mice orally immunized with C501 (pVGS/2SS-asd) had significantly higher levels of anti-SS total IgG and IgA antibodies than control mice and demonstrated a bias toward Th2-associated responses (IgG1/IgG2a ratio > 1). Safety evaluation indicated that vaccinated mice displayed no abnormal clinical signs and histological changes. Biodistribution result revealed that the GS/2SS message was detected in several examined tissues with the exception of ovary and brain, but was rapidly cleared from the body (approximately 10 days). Furthermore, the risk of integration of plasmid pVGS/2SS-asd into the host cellular genome was considered to be negligible. These results may have important implications for the use of vaccine strain C501 (pVGS/2SS-asd) in domestic animals and prompt new perspectives on the safety of DNA vaccines delivered by attenuated bacteria.     

原发性肝癌患者肿瘤组织生长抑素受体表达与血AFP水平的相关性

背景与目的:生长抑素类似物(somatostatin analogue,SSTA)对部分原发性肝癌(hepatocellular carcinoma,HCC)患者具有一定疗效,但HCC患者肿瘤组织中生长抑素受体(somatostatin receptor,SSTR)表达状况不详,其与血甲胎蛋白(alphafetoprotein,AFP)的相关性也未见探讨.本研究拟了解肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5亚型的表达状况及其与血AFP的相关性.方法:逆转录-聚合酶链反应及免疫组织化学法分别检测人肝癌及肝硬化组织(各40例)SSTR1、SSTR2、SSTR3、SSTR4及SSTR5亚型的mRNA及蛋白表达:酶联免疫吸附试验检测HCC患者肿瘤组织及外周血AFP水平.结果:肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5蛋白阳性率(分别为47.5%、70.0%、50.0%、65.0%及67.5%)显著高于肝硬化组织(分别为55.0%、67.5%、52.5%、60.0%及47.5%).肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5表达与患者血AFP水平呈二次曲线正相关(r依次为0.882、0.901、0.877、0.854、0.903,P＜0.05).血AFP水平在200～800 μg/L范围时,伴有肝癌组织SSTRs的高表达,过低或过高的血AFP水平伴有SSTR低表达.结论:约60%HCC患者的肿瘤组织表达了SSTRs,其表达量明显高于肝硬化组织;15 AFP水平在200-800μg/L的HCC患者伴有肝癌组织SSTRs的高表达,提示为SSTA治疗的适宜候选者.     

胰岛素泵治疗2型糖尿病中联用生长抑素的研究

2型糖尿病(T2DM)发病的两个主要环节是胰岛素抵抗和β细胞功能衰竭。目前研究的是针对糖尿病胰腺β细胞如何更好保护其功能,甚至恢复其功能、延缓其衰竭,以达到更好的临床治疗效果。本研究前瞻性观察胰岛素泵联用生长抑素治疗新诊断T2DM患者C肽恢复情况。现报告如下。1研究对象     

升降汤对小鼠胃肠蠕动及胃肠激素的影响

目的 :探讨中药升降汤对胃肠蠕动的作用及对胃肠激素的影响。方法 :①观察小鼠用升降汤高、中、低剂量灌胃后碳素墨水在小肠的移动长度 ,并与蒸馏水灌胃对照组进行对比观察 ;②用放射免疫分析法同步测定升降汤灌胃 1 0d后 ,小鼠小肠组织胃动素和生长抑素水平。结果 :升降汤高、中、低剂量组碳素墨水在小鼠小肠的推进率分别为 ( 96 .1 6± 3.2 7) % ,( 94 .0 2± 3.4 5 ) % ,( 81 .4 2±5 .1 8) % ,对照组为 ( 5 9.2 6± 5 .2 4 ) % ;升降汤组与对照组比较 ,有显著性差异 (P <0 .0 5或P <0 .0 1 )。升降汤高剂量组小肠湿组织胃动素为 ( 8.71± 1 .0 7)ng/g ,生长抑素为 ( 2 4 .0 7±2 .91 )ng/g;对照组分别为 ( 7.5 9± 0 .85 )ng/g ,( 30 .83± 3.6 9)ng/g,两组均有显著性差异 (P<0 .0 5或P <0 .0 1 )。结论 :升降汤可促进小鼠的胃肠蠕动 ,提高小鼠小肠组织的胃动素及降低生长抑素水平     

胃炎康胶囊对慢性胃病患者胃窦D细胞的影响

目的：观察胃炎康胶囊对慢性胃病患生长抑素内分泌细胞(胃窦D细胞)的影响。方法：用免疫组化酶链亲合素过氧化酶复合技术(SABC)对患治疗前后胃黏膜组织的D细胞染色,观察治疗前后D细胞的形态和数量变化。结果：经胃炎康胶囊治疗后,患胃窦黏膜D细胞阳性数及强阳性率均明显下降,差异有显性。结论：胃炎康胶囊对慢性胃病患生长抑素D细胞有调整作用。     

Effect of somatostatin on pancreatic enzyme secretion

The effect of somatostatin (SS) on the pancreatic enzyme secretion was studied in a perfusion system using dispersed pancreatic rat acini in vitro. In addition the effect of SS on pancreatic secretion in vivo was also studied in conscious rats for comparison. In an in vitro study, 6×10^-7M SS-14 caused no significant change in amylase release when added 20 min before stimulation by 10^-5M carbamylcholine (Cch), 10^-6M A23187, 5×10^-7M secretin and 2mM dibutyryl cyclic AMP. The addition of 6×10^-7M SS-28 also caused no significant change in amylase release stimulated by 10^-5M Cch. High performance liquid chromatographic examination indicated that no degradation of either SS-14 or SS-28 occurred after reaction with dispersed acini. In an in vivo study SS-14 caused marked inhibition of basal pancreatic secretion and stimulated pancreatic secretion by bile-pancreatic juice diversion. These results indicate that SS has no direct inhibitory action on rat pancreatic secretion, and that SS may inhibit the pancreatic secretion by indirect mechanisms.     

内镜与生长抑素联合治疗食管静脉曲张出血

目的　观察内镜下治疗和生长抑素（ Ｓ Ｓ）联合对食管静脉曲张出血的短期止血效果。方法　病人分二组, Ｓ Ｓ组在急诊内镜前后连续用 Ｓ Ｓ ５ 天;联合组在 Ｓ Ｓ基础上加行内镜下硬化剂或套扎,但内镜４８ 小时后停用 Ｓ Ｓ。结果　硬化剂３７ 例和套扎３２ 例共计６９ 例的联合组与６４ 例 Ｓ Ｓ组间具可比性。在需气囊压迫、最初止血率、再出血率和死亡率方面,联合组的效果显著优于 Ｓ Ｓ组。二组间的输出血量差异不显著。结论　与单纯 Ｓ Ｓ治疗相比,内镜治疗和 Ｓ Ｓ联合可减少气囊压迫的需求,提高止血率,降低再出血率,进而降低死亡率。     

生长抑素与硫酸镁联合治疗重症急性胰腺炎临床观察

目的 观察联合生长抑素和硫酸镁治疗重症急性胰腺炎(SAP)的疗效.方法 56例SAP患者随机分为联合生长抑素与口服硫酸镁治疗组(n=29)和生长抑素组(n=27),比较两组间入院时与治疗3d及5 d后血、尿淀粉酶及白细胞水平的差值的差异,比较两组腹痛、腹胀、发热、禁食、住院的时长及并发症发生率差异.结果 联合治疗组治疗3d和5 d后,血、尿淀粉酶及白细胞水平的下降幅度均高于生长抑素组(P＜0.05).联合治疗组腹痛、腹胀、发热、禁食、住院的时长和并发症发生率均小于生长抑素组(P＜0.05).结论 联合生长抑素和口服硫酸镁治疗SAP是一种疗效可靠、简便易行的方法,值得推广.     

隔药灸神阙八阵穴对术后粘连性肠梗阻患者疗效及炎性反应因子的影响

目的：探讨隔药灸神阙八阵穴对术后粘连性肠梗阻（AIO）患者疗效及血清白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平的影响。方法：选取2013年1月至2017年4月唐山市人民医院收治的行腹腔手术患者280例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组140例,对照组采用常规治疗;观察组在对照组基础上给予隔药灸神阙八阵穴,均治疗1周。比较2组患者临床疗效、治疗后肠功能评分、治疗前后胃动素（MOT）水平、IL-6、TNF-α水平。结果：观察组总有效率为91.43%,显著高于对照组77.14%（P<0.05）;治疗后,观察组恢复排气时间、腹部症状缓解时间、肠鸣音恢复时间均短于对照组（P<0.05）、2组患者MOT水平均低于治疗前,且观察组的MOT水平低于对照组（P<0.05）、2组患者的血清IL-6、TNF-α水平均显著低于治疗前,且观察组的血清IL-6、TNF-α水平均低于对照组（P<0.05）。结论：隔药灸神阙八阵穴治疗AIO疗效显著,能改善患者胃肠功能,降低MOT水平,有效调节血清IL-6、TNF-α水平。