胰腺激素对肝细胞DNA合成影响的实验观察

以CCl_4复制成大鼠急性肝细胞坏死模型,用单克隆抗溴脱氧脲嘧啶标记DNA技术,体内观察了胰腺激素对肝细胞DNA合成的影响,结果表明,胰高血糖素对肝细胞DNA合成具有一定的刺激作用,投予胰高血糖素后,DNA合成期细胞标记指数从对照组的0.04±0.02增高至7.40±1.61(P<0.01)。而胰岛素单独使用时对肝细胞再生无明显影响。

成熟的肝脏干细胞体外转分化为产生胰腺内分泌激素的细胞

在胚胎发生过程中,肝脏和腹侧胰腺来源于胚胎内胚层的同一细胞群,可以假定胰腺和肝脏内的上皮细胞群可能来源于共同的干细胞群,已有证据表明胰腺干细胞拥有分化成肝细胞的能力,然而,肝脏干细胞分化成胰腺细胞(特别是内分泌胰腺细胞)的能力还不为人所知。 材料和方法:按Petersen等所描述的步骤用2-乙酰胺基笏/肝损伤模型在体内激活肝卵圆细胞,然后用Seglen的二步胶原酶灌注法分离,再通过细胞分类纯化获得Thyl.1-阳性细胞群,纯化的Thyl.

胰泌素增强MRI对胰腺外分泌功能诊断的系统评价和Meta分析

目的系统评价胰泌素增强MRI胰胆管成像(S-MRCP)诊断胰腺外分泌功能的准确性。资料与方法采用计算机检索Cochrane图书馆、Medline、EMbase、中国生物医学文献数据库(CBM)、Pub Med、EBSCO、Ovid、Springer、中国知网(CNKI)、万方和维普数据库1997年1月—2013年12月国内外公开发表的关于S-MRCP评估胰腺外分泌功能的相关文献。由2名高年资影像科医师按照纳入及排除标准独立选择文献并根据QUADAS评价条目标准进行质量评价。采用Meta-Disc软件进行Meta分析,绘制森林图及汇总受试者工作特征曲线。结果共检索到99篇文献,6篇符合纳入标准,纳入的6篇文献具有同质性(I^2<50%,P>0.05),使用固定效应模型计算出的汇总敏感度、特异度分别为0.79(95%CI 0.68~0.88)和0.91(95%CI0.86~0.94)。汇总受试者工作特征曲线下面积为0.9188。结论 S-MRCP对胰腺外分泌功能具有较高的诊断效能。

抗胰岛素抗体是胰腺移植后低血糖的原因之一

据报道,一半以上的胰腺移植(PTX)受者有低血糖症状。为了更好地了解这种低血糖的发生机制,我们研究了PTX 之后有或无低血糖病人的葡萄糖和胰腺激素对 Sus-tacal 的反应。作者对12名 PTX 后有确定的。

《激素免疫分析与临床》

主编:王新华,李廷伟,等定价:49元购买:人民军医出版社010-51927252王兰本书由多位临床检验专家共同编写。全书共分12章,包括技术篇与临床篇。技术篇重点介绍了放射免疫技术、免疫放射技术、酶免疫分析技术、化学发光免疫分析技术、时间分辨免疫荧光分析技术的原理、对激素的免疫分析质量控制等知识。临床篇重点介绍了临床检验中常见的垂体激素、性腺激素。

后腹腔镜CO_2气腹手术时机体神经内分泌的改变

目的观察CO2气腹后腹腔镜手术患者神经内分泌的变化。方法选择后腹腔镜患者23例,手术时间均在1h左右,于气腹前10min和气腹后30min、1h或拆气前以及放气后30min、1h分别采取静脉血测血清甲状腺激素、皮质醇、胰岛激素的变化。结果 CO2气腹术中皮质醇激素明显升高(P<0.05),甲状腺激素、胰岛激素术中有变化,但无统计学意义。结论泌尿外科后腹腔镜手术期间患者皮质醇激素增高,提示后腹腔镜术中亦存在的应激反应,因此缩短手术时间、施行非气腹手术或降低气腹压是适宜的。

慢性胰腺炎患者胰腺相关性内分泌激素的代谢水平

目的检测慢性胰腺炎（CP）患者胰腺相关性内分泌激素的代谢水平，探讨这些激素在CP并发糖尿病过程中的作用。 方法按照纳入和排除标准，连续性纳入2016年2月至2016年8月间第二军医大学长海医院消化内科收治的CP患者，以年龄、性别相匹配的体检健康者作为对照组。CP患者根据基本资料以及检测指标又分为CP糖代谢异常组和CP糖代谢正常组；酒精性CP组和非酒精性CP组。检测空腹血糖、三酰甘油（TG）、总胆固醇（TC）、胰高血糖素样肽-1（GLP-1）、胰多肽（PP）、胰高血糖素、胰泌素、生长抑素水平，分析比较各组间的差异。 结果最终纳入CP患者53例，健康对照者8例；CP糖代谢异常34例，CP糖代谢正常19例；酒精性CP 19例，非酒精性CP 34例。CP组患者空腹血糖高于对照组[（6.69±2.57）mmol/L比（5.42±0.40）mmol/L]，胰泌素水平低于对照组[（10.1±3.7）ng/L比（18.2±4.6）ng/L]，差异均有统计学意义（P值均〈0.05）；与CP糖代谢正常组比较，CP糖代谢异常组饮酒人数多（47.1%比15.8%），空腹血糖[（7.79±2.60）mmol/L比（4.71±0.42）mmol/L]及GLP-1水平高（112±24）ng/L比（97±25）ng/L], TG[（1.23±0.55）mmol/L比（1.71±0.99）mmol/L]及生长抑素水平低[（44.8±7.6）mmol/L比（47.1±7.3）mmol/L]，差异均有统计学意义（P值均〈0.05）；酒精性CP组男性占比（100%比58.8%）、糖代谢异常发生率（84.2%比52.9%）显著高于非酒精性CP组，差异均有统计学意义（P〈0.05或〈0.01）。其他指标各组间的差异均无统计学意义。 结论CP患者除胰岛功能异常外，常合并胰泌素、GLP-1、生长抑素等内分泌激素代谢的异常。长期大量饮酒与CP并发糖代谢异常具有明显的相关性。

胰高血糖素及葡萄糖对培养的兔主动脉平滑肌细胞增殖的影响

为了解胰高血糖素及葡萄糖在动脉粥样硬化中所起的作用,运用细胞培弄手段,对伴和不伴高脂血清培养的兔主动脉平滑肌细胞进行细胞形态学和细胞动力学研究,结果显示:(1)不同浓度胰高血糖素均引起一定程度的细胞蜕变,但蜕变程度无剂量依赖性,而5%高脂血清复合胰高血糖素可造成细胞明显的增殖反应,形态学上表现为大量线粒体、核糖核蛋白体增生,多量幼稚胶原纤维生成。(2)不同浓度葡萄糖均引起细胞增殖抑制,抑制程度与葡萄糖浓度成正比(相关性检验r=-0.79,P<0.01);高脂血清复合葡萄糖对细胞增殖影响亦如单纯葡萄糖组(相关性检验r=-0.59,P<0.01),可见葡萄糖与高脂血清对平滑肌细胞增殖的影响无正的协调作用。上述结果提示:高脂血清伴血浆胰高血糖素浓度增高,可促进动脉粥样硬化的形成和发展,高浓度葡萄糖能引起平滑肌细胞的损伤。

脑卒中患者内分泌代谢改变

脑卒中(stroke),又称"中风""脑血管意外",包括缺血性和出血性卒中,是由于脑血管阻塞或脑血管突然破裂导致血液不能流入大脑而引起脑组织缺血或坏死的一组疾病。特点为高发病率,高致残率和高死亡率,城乡合计脑卒中已成为我国第一位死亡原因,也是中国成年人残疾的首要原因,因此,早期准确评估脑卒中患者预后,有助于患者早期功能康复、心理辅导,还能更好的开放治疗新策略及优化医疗资源的利用。近年脑血管病的神经内分泌变化日益受到业界重视,研究发现卒中后患者内分泌代谢紊乱可造成神经细胞凋亡、脑水肿或血管痉挛等,加重神经系统损伤,影响患者预后。本文对脑卒中患者内分泌代谢改变做一综述。

Sanofi--Aventis公司购买Pancreate的全球权利

法国Sanofi～Aventis公司与美国CureDM公司签订新型的人肽Pancreate（Ⅰ）的转让协议。（Ⅰ）可使1型及2型糖尿病患者恢复胰岛素及其他胰腺激素的产生能力。

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

AIM： To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine （L-Arg） -induced experimental pancreatitis in rats. METHODS： Male Wistar rats （25） were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS： L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio （pw/bw）, the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes （Cu/Zn-superoxide dismutase （CulZn-SOD） and catalase （CAT）） were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION： Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

Octreotide reverses shock due to vasoactive intestinal peptide-secreting adrenal pheochromocytoma: A case report and review of literature

Vasoactive intestinal peptide-producing tumors （VIP-oma） usually originate in the pancreas and are chara-cterized by diarrhea, hypokalemia, and achlorhydria （WDHA syndrome）. In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, fushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, fushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding;and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confrmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health andwas symptom-free.

Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats

AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

Serum measurements of testosterone, insulin-like growth factor 1, and insulin-like growth factor binding protein-3 in the diagnosis of prostate cancer among Korean men

Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）

Mechanism for Src activation by the CCK2 receptor:Patho-physiological functions of this receptor in pancreas

AIM： TO investigate in vivo, whether CCK2 receptors （CCK2R） regulate proteins known to play a crucial role in cell proliferation and cancer development and analyse in vitro the molecular mechanisms that lead to Src activation; in particular, to identify the domains within the CCK2R sequence that are implicated in this activation. METHODS： The expression and activation of Src and ERK were studied in vivo using immunofluorescence and western-blot techniques. We used pancreatic tissues derived from wild type or Elas-CCK2 mice that expressed the CCK2R in pancreatic acini, displayed an increased pancreatic growth and developed preneoplastic lesions. The pancreatic tumor cell line AR4-2J expressing the endogenous CCK2R or COS-7 cells transiently transfected with wild type or mutant CCK2R were used as in vitro models to study the mechanism of Src activation. Src activation was measured by in vitro kinase assays, ERK activation by western blot using antiphospho-ERK antibodies and the involvement of Src in gastrin-induced cell proliferation by MTT test. RESULTS： We showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, led to the activation of Src and the ERK pathway. Src was activated upstream of the ERK pathway by the CCK2R in pancreatic tumoral cells and contributed to the proliferative effects mediated by this receptor. In vitro results demonstrated that activation of the Src/ERK pathway by the CCK2R required the NPXXY motif, located within the CCK2R sequence at the end of the 7^th transmembrane domain, and suggested the putative role of Gq in this mechanism. CONCLUSION： Deregulation of the Src/ERK pathway by the CCK2R might represent an early step that contributes to cell proliferation, formation of preneoplastic lesions and pancreatic tumor development.

Comparison of integrated Chinese and Western medicine with and without somatostatin supplement in the treatment of severe acute pancreatitis

AIM: To evaluate the therapeutic effect of the combined use of early short-term somatostatin and conventional integrated Chinese and Western medicine in treating severe acute pancreatitis. METHODS: Sixty patients with severe acute pancreatitis were divided at random into a somatostatin group and a basic treatment group. Both groups received integrated traditional Chinese and Western medicine without surgery. For patients in the somatostatin group, somatostatin was infused intravenously 250 μg/h for 72 h; other medications were the same as in the basic treatment group. In both groups, comparisons of therapeutic effectiveness were made in terms of morbidity of organic dysfunction and mortality rate, and severity of the disease according to serum levels of C-reaction protein, scores of acute physiology and chronic health evaluation (APACHE Ⅱ), and scores of Balthazar-CT. RESULTS: The indexes for C-reaction protein levels on the fourth and seventh clays, and APACHE II scores on the seventh day after treatment, were significantly improved in the somatostatin group than in the basic treatment group. The morbidity of organic dysfunction was lower in the somatostatin group than in the basic treatment group, although the difference was not statistically significant. There was no significant difference in mortality between the two groups. CONCLUSION: We conclude that combined traditional Chinese and Western medicines with an early short-term use of somatostatin can improve the condition of patients with severe acute pancreatitis.

Presence of CCK-A, B receptors and effect of gastrin and cholecystokinin on growth of pancreatobiliary cancer cell lines

AIM: To investigate the effects of gastrin and cholecystokinin (CCK) and their specific antagonists on the growth of pancreatic and biliary tract cancer cell lines. METHODS: Five pancreatic and 6 biliary cancer cell lines with 2 conrtol cells were used in this study. Cell proliferation study was done using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test and direct cell count method. Reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization were performed to examine and quantify the expression of hormonal receptors in these cell lines. RESULTS: SNU-308 showed a growth stimulating effect by gastrin-17, as did SNU-478 by both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). Other cell lines did not respond to gastrin or CCK. In RT-PCR, the presence of CCK-A receptor and CCK-B/gastrin receptor mRNA was detected in all biliary and pancreatic cancer cell lines. In slot blot hybridization, compared to the cell lines which did not respond to hormones, those that responded to hormones showed high expression of receptor mRNA. CONCLUSION: Gastrin and CCK exert a trophic action on some of the biliary tract cancers.