Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes

Progressive deterioration of beta-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive beta-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n=62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration > or = 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at Oh and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.     

Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production

It has been suggested that one key feature of mitochondrial permeability transition (PT) regulation is its control by the proton electrochemical gradient and that depolarization favors pore opening, swelling, and reactive oxygen species (ROS) production. Moreover, ROS have been suggested to facilitate the process of mitochondrial PT pore opening. The aim of this study was to show that collapsing the mitochondrial membrane potential with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), at concentrations of up to 10 microM, does not induce mitochondrial swelling and, in fact, stabilizes mitochondria exposed to oxidant, protecting them from tert-butyl hydroperoxide (TBH)-induced high-amplitude swelling. FCCP decreased polyethylene glycol-induced mitochondrial contraction following exposure to TBH, indicating closing of the PT mega-channel. In the presence of the calcium uniporter inhibitor ruthenium red, FCCP induced PT due to suppression of calcium efflux. Under PT-favorable conditions, ROS production was evaluated in mitochondria following treatments with TBH, inorganic phosphate, or FCCP (with or without ruthenium red). FCCP alone and in combination with ruthenium red attenuated mitochondria-derived ROS production. FCCP also decreased the augmented ROS production induced by inorganic phosphate. It is concluded that mitochondrial depolarization protects and prevents high-amplitude swelling and PT-derived ROS production.     

Surgical Treatment and Proposed Modified Classification for Harrington Class III Periacetabular Metastases

ObjectivesThis study aims to: (i) evaluate the outcome of patients with Harrington class III lesions who were treated according to Harrington classification; (ii) propose a modified surgical classification for Harrington class III lesions; and (iii) assess the efficiency of the proposed modified classification.MethodsThis study composes two phases. During phase 1 (2006 to 2011), the clinical data of 16 patients with Harrington class III lesions who were treated by intralesional excision followed by reconstruction of antegrade/retrograde Steinmann pins/screws with cemented total hip arthroplasty (Harrington/modified Harrington procedure) were retrospectively reviewed and further analyzed synthetically to design a modified surgical classification system. In phase 2 (2013 to 2019), 62 patients with Harrington class III lesions were classified and surgically treated according to our modified classification. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. The outcome of local control was described using 2‐year recurrence‐free survival (RFS). Owing to the limited sample size, we considered P < 0.1 as significant.ResultsIn phase 1, the mean surgical time was 273.1 (180 to 390) min and the mean intraoperative hemorrhage was 2425.0 (400.0 to 8000.0) mL, respectively. The mean follow‐up time was 18.5 (2 to 54) months. Recurrence was found in 4 patients and the 2‐year RFS rate was 62.4% (95% confidence interval [CI] 31.6% to 93.2%). The mean postoperative MSTS93 score was 56.5% (20% to 90%). Based on the periacetabular bone destruction, we categorized the lesions into two subgroups: with the bone destruction distal to or around the inferior border of the sacroiliac joint (IIIa) and the bone destruction extended proximal to inferior border of the sacroiliac joint (IIIb). Six patients with IIIb lesions had significant prolonged surgical time (313.3 vs 249.0 min, P = 0.022), massive intraoperative hemorrhage (3533.3 vs 1760.0 mL, P = 0.093), poor functional outcome (46.7% vs 62.3%, P = 0.093), and unfavorable local control (31.3% vs 80.0%, P = 0.037) compared to the 10 patients with IIIa lesions. We then modified the surgical strategy for two subgroup of class III lesions: Harrington/modified Harrington procedure for IIIa lesions and en bloc resection followed by modular hemipelvic endoprosthesis replacement for IIIb lesions. Using the proposed modified surgical classification, 62 patients in the phase 2 study demonstrated improved surgical time (245.3 min, P = 0.086), intraoperative hemorrhage (1466.0 mL, P = 0.092), postoperative MSTS 93 scores (65.3%, P = 0.067), and 2‐year RFS rate (91.3%, P = 0.002) during a mean follow‐up time of 19.9 (1 to 60) months compared to those in the phase 1 study.ConclusionThe Harrington surgical classification is insufficient for class III lesions. We proposed modification of the classification for Harrington class III lesions by adding two subgroups and corresponding surgical strategies according to the involvement of bone destruction. Our proposed modified classification showed significant improvement in functional outcome and local control, along with acceptable surgical complexity in surgical management for Harrington class III lesions.     

俄歇电子发射体67Ga-EDTMP 对骨肉瘤细胞株辐射效应的形态学变化

目的　研究俄歇电子发射体67Ga-EDTMP对人骨肉瘤细胞株 (HOS - 86 0 3)的辐射效应 ,探讨67Ga作为原发肿瘤和骨转移癌内照射治疗核素的可能性。方法　用成集落实验和透射电镜研究受照细胞的形态变化。结果　发现67Ga-EDTMP对肿瘤细胞有明显的杀伤和抑制增殖作用 ,并随剂量的加大 ,抑制效率增加 ;倒置显微镜下细胞集落数量减少 ,集落偏小 ,细胞稀疏。电镜下胞浆中空泡形成 ,细胞溶解、坏死 ,细胞核固缩 ,出现典型的细胞凋亡改变 ,形成凋亡小体。结论　67Ga可能是一种有前途的骨肉瘤和骨转移癌的放射性治疗核素     

The tumorigenic phenotype of a mutated form of Fc gamma RIIB1, lacking the ability to generate soluble receptor and allowing a low-level of ligand binding

Non immunohematopoietic murine tumor cells ectopically expressing Fc gamma RIIB1 (B1) were recently shown to express a higher tumorigenicity phenotype than cells not expressing this receptor. Utilizing a genetic approach we studied the possible contribution of a soluble form of B1 to tumor enhancement. A mutated form of the B1, lacking the cleavage site responsible for the generation of soluble B1 was produced using gene splicing by overlap extension PCR. A deletion confirmed by sequence analysis from 172 to 178 residues was generated. Stable transfectants expressed the B1 deleted form (B1 Delta) both as specific RNA and as a membrane protein receptor allowing a low level of ligand binding. The soluble form of B1 was undetectable in tissue culture supernatants of Bib transfected cells while it was present in supernatants of wild type B1-transfectants. Stable B1 Delta transfectants were significantly more tumorigenic than negative control transfectants. Tumor incidence was almost as high as that of intact B1 and lagged in the latency period before the appearance of palpable tumors. It is suggested that the soluble B1 has a minimal contribution to tumor enhancement.     

与经皮腹膜后隙脾肾静脉分流术有关的形态学观测

目的为经皮腹膜后隙牌肾静脉分流术（PRESS）技术的开发提供形态学依据。方法选取30例经甲醛固定的成人尸体标本,观察牌静脉、左肾静脉的走行及两者之间的关系,并对相关数据进行测量。结果牌静脉紧靠肠系膜上动脉起端右前方与肠系膜上静脉汇合为门静脉,脾静脉与左肾静脉在肠系膜上动脉起点左侧位置关系较为恒定。结论经股静脉的插管须先进入左肾静脉,然后在肠系膜上动脉起端左侧穿向脾静脉。     

An outbreak of Molluscum contagiosum in a kibbutz

Summary Molluscum contagiosum is a viral disease that presents in a primary care setting as single or multiple wart-like lesions. We have seen an outbreak of Molluscum contagiosum in a small rural community, affecting 34 individuals. The most infected were children two-to nine-years-old. The diagnosis was made on clinical grounds. Spread appeared to be as a result of direct contact and by fomites. There was no evidence, in our study, of spread via swimming pool. Cryosurgery was used to treat our patients with Molluscum contagiosum.

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Ausbruch von Molluscum contagiosum in einem Kibbuz

Zusammenfassung Molluscum contagiosum ist eine virale Erkrankung, die bei Fällen, die in der Allgemeinpraxis beobachtet werden, mit einzelnen oder zahlreichen warzenähnlichen Läsionen auftritt. Wir haben in einer kleinen ländlichen Gemeinde einen Ausbruch von Molluscum contagiosum mit 34 Fällen beobachtet. Betroffen waren vor allem Kinder im Alter von zwei bis neun Jahren. Die Diagnose wurde klinisch gestellt. Die Übertragung erfolgte offensichtlich durch direkten Kontakt und kontaminierte Materialien. Für eine Übertragung im Swimming Pool ergab sich kein Anhalt. Zur Behandlung der Molluscum contagiosum-Läsionen wurde bei unseren Patienten Kryochirurgie eingesetzt.

     

茯苓萜类的高效液相色谱指纹图谱研究

目的 建立茯苓三萜化合物的指纹图谱。方法 反相高效液相色谱法。结果 道地药材茯苓及不同地区收集的市场商品具有相当稳定的、相似程度很高的指纹图谱。结论 可利用液相色谱的特征峰控制茯苓及其制剂的质量。