Exendin-4与β细胞功能

胰岛β细胞的数目减少和（或）分泌功能障碍是导致2型糖尿病发病的中心环节。β细胞凋亡异常增多及β细胞分裂、增殖和分化障碍是导致β细胞数目减少的重要原因。有效抑制β细胞凋亡，增加2型糖尿病患者β细胞总量，将为2型糖尿病防治开辟新途径。因此，减少β细胞凋亡、促进β细胞的增生、分化，增加β细胞数量的治疗方法将成为糖尿病研究领域的重点。近年研究发现胰升糖素样肽1（GLP-1）和Exendin-4（Ex-4）能够刺激β细胞新生和增生、抑制β细胞凋亡，从而增加胰岛β细胞数量，促进胰岛素合成及分泌。于是，GLP-1和Ex-4成为糖尿病治疗研究的新热点。本文就Ex-4对胰岛β细胞功能影响的研究进展作一综述。     

β细胞功能障碍：从理论到实践再到理论

机体内胰岛β细胞数量通过细胞增殖、增生以及细胞凋亡、坏死或萎缩来维持动态平衡，胰岛β细胞功能障碍是2型糖尿病的核心异常。母亲患糖尿病对后代的影响是宫内暴露于高血糖导致的环境因素改变所致，但对于大多数糖尿病患者来说基因和环境因素的共同影响构成了糖尿病的发病基础，只是所占的比例不同。胰升糖素样肽-1具有促进胰岛β细胞新生的作用，可能会成为未来糖尿病治疗领域的新药物。     

血小板反应蛋白-1：对胰岛β细胞功能有重要意义的胰岛内皮细胞信号

既往研究发现，胰岛血小板反应蛋白-1缺失可引起胰岛增生。一项发表在Diabetes上的研究证实，内皮源型血小板反应蛋白-1对胰岛β细胞功能具有重要影响。     

胰岛细胞增生症与胰腺内分泌部增生

胰岛细胞增生症一直被认为是一种引起婴儿高胰岛素血症的疾病。但在此病的定义和诊断标准方面存在争议。作者对几组胰内分泌部进行了研究,它们包括:①正常胰腺(从胎儿至成人,49例);②胰岛细胞增生症的胰腺(5例);③成人胰岛素瘤旁组织(8例)。用免疫组化及形态学测量方法重点观察了导管内分泌细胞增生、弥漫性内分泌细胞增生和间隔内胰岛等现象,测量了总内分泌区(TEA)和胰岛大小及胰岛内部内分泌细胞分布类型。     

胰岛素受体的自家抗体导致胰岛β细胞增生

包括胰岛母细胞增生症在内的胰岛细胞增生常由于产生过多的胰岛素而导致低血糖。然而在所谓先天性异常的Donohu’s病中胰岛细胞增生也可继发于对胰岛素的耐受。本文报导一例自家抗体阻断胰岛素受体引起的高血糖的胰岛β细胞增生。 女性,40岁,死前患糖尿病19个月。无糖尿病家族史。每天用2,000单位的高剂量胰岛素治疗,仍有糖尿存在。双手、颈部、背部、腋窝及股部皮肤增厚,有棘皮症的色素斑,表浅软组织钙化,肺功     

猪胚胎胰岛移植治疗实验性糖尿病的研究

采用胶原酶消化和体外培养的方法，成功获得大量猪胚胎胰岛，将胰岛移植到裸鼠肾包膜下，3周后静脉注射STZ，诱导实验性糖尿病。自移植起平均75．9±36．6天后，血糖恢复正常。将移植物取出后，裸鼠均复发糖尿病。组织学检查发现，移植物中含大量的胰岛、管型、β细胞团和血管，而胰腺组织切片见β细胞消失，未见胰岛细胞自发性增生。本研究结果显示：猪胚胎胰岛在裸鼠体内能衍化发育成熟，并具有控制血糖稳定的功能。此结果也证实STZ对未成熟的猪胚胎胰岛无毒性作用。     

胰岛B细胞瘤的诊疗进展

胰岛B细胞瘤在胰岛细胞瘤中最为常见，占全部胰岛内分泌肿瘤中的70％～75％。本病既可发生于数月的婴儿，亦可发生于80岁的老年人，多见于40～50岁的青壮年；男女发病率无明显差异。发病率报道不一，总体年发病率为1／100万～5／100万。随着医生对本病认识的提高和诊疗技术的进步，发病率有增长的趋势。95％的胰岛B细胞瘤为良性腺瘤。本病的病变类型可以分为胰岛B细胞增生、细胞癌和家族性多发性内分泌肿瘤1（MEN1），在儿童中可见一种特殊类型为胰岛细胞弥漫性增生。关于MEN1的发生率国外报道（4％）高于国内（1．33％），可能与国内对MEN1认识欠缺以及人种差异有关。     

β细胞功能障碍:从理论到实践再到理论

机体内胰岛β细胞数量通过细胞增殖、增生以及细胞凋亡、坏死或萎缩来维持动态平衡,胰岛β细胞功能障碍是2型糖尿病的核心异常。母亲患糖尿病对后代的影响是宫内暴露于高血糖导致的环境因素改变所致,但对于大多数糖尿病患者来说基因和环境因素的共同影响构成了糖尿病的发病基础,只是所占的比例不同。胰升糖素样肽1具有促进胰岛β细胞新生的作用,可能会成为未来糖尿病治疗领域的新药物。     

GAD预防NOD鼠胰岛炎和糖尿病的机理研究：———胰岛细胞Bcl—2,PCN …

目的 应用自制猪脑ＧＡＤ研究其预防ＮＯＤ鼠胰岛炎和糖尿病作用及其作用。方法 ＮＯＤ鼠动物模型、病理形态学研究及胰岛细胞Ｂｃｌ－２、ＰＣＮＡ免疫组化研究。结果 ＧＡＤ能 明显地减轻ＤＯＤ鼠胰岛炎发生程度和糖尿病发生率，ＧＡＤ能诱导或维持胰岛β细胞Ｂｃｌ－２蛋白表达水平，且ＧＡＤ在维持ＮＯＤ鼠早期胰岛β细胞增殖与凋亡动态平衡方面可能有重要作用；胰岛β细胞增殖主要与β细胞本身增生代偿能力有关，与ＧＡＤ无     

IGF-1的免疫调节作用

Ｔ细胞、Ｂ细胞等多种免疫细胞表面存在ＩＧＦ１受体，也以自分泌和／或旁分泌的方式产生ＩＧＦ１。ＩＧＦ１具有促进淋巴组织增生、调节Ｔ细胞生长、分化和效应完成、控制胸腺素功能等免疫调节作用，并能使Ⅰ型糖尿病动物和患者缺陷的ＣＤ８＋Ｔ细胞增生，恢复ＣＤ４＋／ＣＤ８＋Ｔ细胞亚群比例平衡，从而中止自身免疫反应，保护胰岛β细胞。ＩＧＦ１有望用作Ⅰ型糖尿病的预防药物，对这方面的进展作了简要综述。     

Calcium channel antagonists part V: Second-generation agents

Summary Second-generation agents include new dihydropyridines, such as amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, and nitrendipine. Verapamil-like agents include tiapamil, gallopamil, and anipamil. Among the diphenylalkylamines, bepridil is of special interest. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. From all these agents will be selected those that are longer-acting and provide higher vascular selectivity.     

Immunoglobulin allotypes are not associated with HLA-antigens,autoantibodies and clinical symptoms in systemic lupus erythematosus

Summary Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.E. Albert, M. Baur, A. Corvetta, H. Deicher, J. Frey, F. Krapf, B. Lang, J. R. Kalden, H. J. Lakomek, H. H. Peter, C. Rittner, P. Schneider, S. Seuchter, P. Späth     

Cinedefecography and electromyography in the diagnosis of nonrelaxing puborectalis syndrome

A prospective study was undertaken to assess the correlation between electromyography (EMG) and cinedefecography (CD) for the diagnosis of nonrelaxing puborectalis syndrome (NRPR). Clinical criteria for NRPR included straining, incomplete evacuation, tenesmus, and the need for enemas, suppositories, or digitation. EMG criteria included failure to achieve a significant decrease in electrical activity of the puborectalis (PR) during attempted evacuation. CD criteria included either paradoxical contraction or failure of relaxation of the PR along with incomplete evacuation. In addition, other etiologies for incomplete evacuation, such as rectoanal intussusception or nonemptying rectocele, were excluded by proctoscopy and defecography in all cases. One hundred twelve patients with constipation, 81 females and 31 males, with a mean age of 59 (range, 12–83) years were studied by routine office evaluation, CD, and EMG. Forty-two patients (37 percent) had evidence of NRPR on CD (rectal emptying: none, 24; incomplete, 18). Twenty-eight of these patients (67 percent) also had evidence of NRPR on EMG. EMG findings of NRPR were present in 12 of 70 patients (17 percent) with normal rectal emptying. Conversely, 14 of 72 patients (19 percent) with normal PR relaxation on EMG had an NRPR pattern on CD. The sensitivity and specificity for the EMG diagnosis of NRPR were 67 percent and 83 percent, and the positive and negative predictive values were 70 percent and 80 percent, respectively. Conversely, if EMG is considered as the ideal test for the diagnosis of NRPR, CD had a sensitivity of 70 percent, a specificity of 80 percent, and positive and negative predictive values of 66 percent and 82 percent, respectively. In summary, sensitivity, specificity, and predictive values of EMG and CD are suboptimal. Therefore, a combination of these two tests is suggested for the diagnosis of NRPR.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.Dr. Ger was a visiting colorectal surgeon from the Section of Colon and Rectal Surgery, Department of Surgery, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, R.O.C.     

Calcium channel antagonists part V: Second-generation agents

Summary Second-generation agents include new dihydropyridines, such as amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, and nitrendipine. Verapamil-like agents include tiapamil, gallopamil, and anipamil. Among the diphenylalkylamines, bepridil is of special interest. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. From all these agents will be selected those that are longeracting and provide higher vascular selectivity.[This article appeared in Cardiovascular Drugs and Therapy, 2:191–203, 1988.]     

新疆食虫目动物

作者通过多年实地采集,并整理了本所30年存放的食虫目动物标本。到目前为止,新疆食虫目动物有2科4属7种9亚种。对各个种(亚种)的形态、地理分布和生态学作了记述。猬科Erinaceidae:(1)大耳猬淡色亚种 Hemiechinus auritus albulus Stoliczka,1872(2)大耳猬吐鲁番亚种 Hemiechinus auritusturfanicus Matschie,1911.科 Soricidae;(3)天山Sorex asper Thomas,1914(4)小科克苏河亚种Sorex minutus heptapotamicus Stroganov,1956 (5)西藏指名亚种 Sorex thibetanus thibetanusStroganov,1952(6)白腹蒙古亚种 Crocidura leucodon myoides Blanford,1875(7)白腹阿拉本图亚种Crocidura leucodonHeptapotamicus stroganov,1956(8)小伊犁亚种 Croidura suaveolens ilesisMillev,1901(9)水远东亚种 Neomysfodiens orientis Thomas,1914。     

布鲁菌分子分型方法应用研究进展

布鲁菌属细菌是布病的病原菌。当前,用于布鲁菌属细菌分型的方法有多种,而布鲁菌分子分型方法在布病的分子流行病学调查、病原菌的快速分型鉴定、病原菌的溯源分析和菌株之间差异关系的分析过程中被广泛应用并具有十分重要的作用。本文就常用的布鲁菌的核酸探针技术(DNA probes)、聚合酶链式反应(PCR)、实时定量PCR(Real-time PCR)、16SrDNA鉴定、PCR限制性片段长度多态性( PCR-RFLP)、单核苷酸多态性分析(SNP)、脉冲场凝胶电泳(PFGE)、多位点序列分型(MLST)、多位点串联重复序列分析(VNTR/MLVA)等分子分型方法的应用研究进展予以综述。     

Les atteintes rénales au cours des hémopathies malignes. Stratégie diagnostique

Kidney involvement is frequent in hematologic malignancies. It is associated with adverse outcome and treatment difficulties. It can affect every area of the renal parenchyma (tubules, interstitium, glomerulus, vessels). Various mechanisms could be implicated: deposits of immunoglobulin fractions or crystals, renal infiltration by malignant cells, urinary tract obstruction, paraneoplastic or storage glomerulopathies… Diagnostic strategy relies on the clinical presentation: acute renal failure, chronic kidney disease, glomerular proteinuria with or without nephrotic syndrome, tubular proteinuria, hydroelectrolytic disorders. In this review, we detail the diagnostic tests that are needed for the detection and the follow-up of renal involvement in hematologic malignancies, and clarify the indications of renal biopsy. We propose diagnostic strategies of renal involvement in myeloma, Waldenström's disease, high grade lymphomas and acute leukemias, low grade lymphomas and chronic leukemias. The adverse effects of treatments (chemotherapy, radiotherapy, stem cell graft …) are not addressed in this review.     

How Is the Liver Primed or Sensitized for Alcoholic Liver Disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-α gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFα gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.     

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients

M. Mikulska, V. Del Bono, R. Prinapori, L. Boni, A.M. Raiola, F. Gualandi, M.T. Van Lint, A. Dominietto, T. Lamparelli, P. Cappellano, A. Bacigalupo, C. Viscoli. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.
Transpl Infect Dis 2010: 12: 505–512. All rights reserved Abstract: Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case–control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2–24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65–48.99 and OR=7.52, 95% CI, 1.56–36.31, respectively, P=0.047); severe (grades 3–4) mucositis (OR=9.04, 95% CI, 1.97–41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11–18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93–18.66 for 1–7 days of therapy, and OR=7.31, 95% CI, 1.78–30.12 for 8–23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06–0.97, P=0.045 and OR=0.11, 95% CI, 0.02–0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.     

Étiologies et orientation diagnostique devant un flush

The flush is a transient and recurrent erythema of the upper region of the body, due to a sudden arterial dilatation. First, physicians should confirm the flush and ascertain the location and timing of skin manifestations. The rapid onset and location of the skin rash to the face and anterior chest are the main characteristics of flush. In most of the cases, the flush is emotional, but this should remain a diagnosis of exclusion, as flush may be the presenting manifestation of many systemic or neoplastic disorders. Therefore, a comprehensive diagnostic work-up is necessary, including clinical, biological, and imaging testing. Neoplastic and endocrine causes of flush include VIPoma, carcinoid syndrome, medullary thyroid cancer, mastocytosis, renal cell carcinoma, and pheochromocytoma. Mast cell activation syndrome has been recently described, but it remains a diagnosis of exclusion. This review will first present the different causes of flush, and then will propose a diagnostic algorithm for the physician.