Citrate and vitamin E blunt the shock wave-induced free radical surge in an in vitro cell culture model

Free radical formation plays a major role in shock wave lithotripsy induced renal damage. Moreover, previous studies suggest that free radicals may also promote de novo calcium oxalate crystallization of previously damaged urothelium. Citrate is a known inhibitor of renal stone formation and has also been used as a free radical scavenger. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of two free radical scavengers, citrate and vitamin E, on the prevention of the shock wave-induced free radical surge. Suspensions of MDCK cells were placed in containers for shock wave exposure. Six groups of six containers each were examined: (a) no scavengers 0 shocks, (b) no scavengers 100 shocks, (c) citrate 0 shocks, (d) citrate 100 shocks, (e) vitamin E 0 shocks, (f) vitamin E 100 shocks. An unmodified HM3 was used to deliver 100 shocks at 24 kV. The cell groups that were not shocked acted as the control group and were handled identically, except for the lack of shock wave exposure. After shock wave administration, the containers were emptied and cell suspensions were immediately centrifuged. The supernatant was examined for lactate dehydrogenase (LDH) and 8-isoprostane (8-IP), markers of cellular injury and free radical formation, respectively. Intracellular LDH uniformly increased in all groups exposed to shock wave energy. Similarly, 8-IP increased in all shocked groups. However, the 8-IP increase was significantly reduced when the free radical scavengers were employed. As citrate is a well-known inhibitor of calcium nephrolithiasis, its mechanism of action may be further enhanced, based on its ability to reduce free radical formation, by a protective effect on the urothelium. These data further support the use of citrate based medications during the peri-operative period of shock wave lithotripsy, not only to inhibit stone formation and facilitate fragment passage, but also to reduce the incidence of shock wave induced renal damage. Further studies are warranted to clinically test this hypothesis.     

Clinical and protein metabolic efficacy of glutamine granules-supplemented enteral nutrition in severely burned patients

As an abundant amino acid in the human body, glutamine has many important metabolic roles that may protect or promote tissue integrity and enhance the immune system. A relative deficiency of glutamine in such patients could compromise recovery and result in prolonged illness and an increase in late mortality. The purpose of this clinical study is to observe the effects of enteral supplement with glutamine granules on protein metabolism in severely burned patients. Forty-eight severe burn patients (total burn surface area 30-75%, full thickness burn area 20-58%) who met the requirements of the protocol joined this double-blind randomized controlled clinical trial. Patients were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). There was isonitrogenous and isocaloric intake in both groups, glutamine and B group patents were supplemented with glutamine granules or placebo (glycine) at 0.5 g/kg per day for 14 days with oral feeding or tube feeding, respectively. The level of plasma glutamine, plasma protein content, urine nitrogen and urine 3-methylhistidine (3-MTH) excretion were determined, wound healing rate of the burned area and hospital stay were recorded. The results showed that there were significant reductions in plasma glutamine level and abnormal protein metabolism. After supplement with glutamine granules for 14 days, the plasma glutamine concentration was significantly higher than that in B group (607.86+/-147.25 micromol/L versus 447.63+/-132.38 micromol/L, P<0.01) and the plasma prealbumin and transferrin in Gln group were remarkably higher than those in B group (P<0.01), but the concentration of total protein and albumin were not significantly changed compared with B group (P>0.05). On the other hand, the amount of urine nitrogen and 3-MTH excreted in Gln group were significantly lower than that in B group. In addition, wound healing was faster and hospital stay days were shorter in Gln group than B group (46.59+/-12.98 days versus 55.68+/-17.36 days, P<0.05). These indicated that supplement glutamine granules with oral feeding or tube feeding could abate the degree of glutamine depletion, promote protein synthesis, inhibit protein decompose, improve wound healing and reduce hospital stay.     

尾加压素Ⅱ与糖尿病及肾脏疾病

尾加压素Ⅱ(urotensinⅡ,UⅡ)最早是自硬骨鱼的脊髓尾部下垂体中提取的一种生长抑素样环肽,它属于神经肽范围。后来证实其分布具有种属普遍性,从软体动物到哺乳动物的神经系统中均有存在。近来,Coulouarn等首次从人体中克隆出UⅡ。随后,1999年,Ames等在《Nature》上首次报道UⅡ是迄今最强的缩血管肽,它对大鼠胸主动脉和肺动脉的收缩效应分别是内皮素．1的16倍和4倍。     

治疗性克隆与造血干细胞移植

干细胞研究及其在临床的应用是21世纪生命科学研究的主要目标之一。造血干细胞（hematopoietic stem cell,HSC）是目前研究最为清楚的一种成体干细胞,HSC移植在临床上已成功应用,并取得了巨大的社会效益和经济效益。然而,细胞来源不足、移植后需要终生服用免疫抑制剂及其所带来的一系列严重的并发症极大地限制了该技术在临床的广泛开展。     

混合细胞共微囊化对肝细胞功能的支持作用

目的观察大鼠肝细胞、转基因肝星状细胞株HGF／CFSC和／或大鼠骨髓来源Thy-1^＋β2M^-细胞（BDTC）共微囊化对肝细胞生物学活性的支持,及腹腔移植混合细胞微囊对急性肝衰竭大鼠肝功能的改善作用。方法利用微囊发生器制备含肝细胞或混合细胞的微囊,依微囊内包裹细胞种类不同,分为微囊化肝细胞组、微囊化肝细胞＋CFSC／HGF组）和微囊化肝细胞＋CFSC／HGF＋BDTC组,通过观察囊内细胞形态和体外培养测定培养液中白蛋白和尿素的分泌,判断各组囊内肝细胞活性和功能的维持;将90％肝大部切除所致的急性肝衰竭大鼠按照移植微囊种类不同分为空囊对照组和上述3个实验组（每组10只）,观察腹腔植入后不同时间大鼠的一般状况、存活时间、血生化改变、肝组织再生及微囊化移植物的组织学特征。结果与单独肝细胞微囊者相比,混合细胞微囊内肝细胞存活时间超过1倍,培养液中白蛋白分泌和尿素合成量明显增加（均P〈0．01）;与对照组相比,微囊化肝细胞或微囊化混合肝细胞移植后,急性肝衰竭大鼠的肝功能显著改善、存活率明显提高（10／10 vs 1／10）,其肝组织再生完全;移植21—42d时,部分微囊附着于肝脏表面并出现血管化,微囊表面存在不同程度的纤维化,微囊内仍有存活的细胞,以微囊化混合肝细胞组优于微囊化肝细胞组。结论混合细胞共微囊化能明显改善囊内肝细胞的存活寿命、形态和功能的维持,微囊化混合肝细胞腹腔移植对促进急性肝衰竭大鼠的肝功能恢复具有显著作用。     

Use of a refined operative strategy in combination with the multidisciplinary approach to manage blunt juxtahepatic venous injuries

BACKGROUND: Despite continuous advances in traumatology, juxtahepatic venous injuries are still the most difficult and deadly form of liver trauma. Most deaths result from exsanguination, and reported mortality ranges from 50% to 80%. This is an evaluation on our experience with the management of this high mortality injury following a refined operative strategy. METHODS: This is a retrospective study of consecutive patients sustaining blunt juxtahepatic venous injuries. The management for these patients was mainly a refined operative strategy combined with a multidisciplinary approach. Preoperative conditions and the patient demographics were gathered. In addition, the number and type of interventional procedures, overall complications, and operative procedures were collected and analyzed. RESULTS: From January, 1996 to March, 2004, 19 patients (M:F = 13:6) with juxtahepatic venous injuries were included and all were managed operatively. The operative procedures included hepatectomy by finger fracture technique for direct repair (8), perihepatic packing (1), packing and hepatic artery embolization (1), packing and hepatic artery ligation (1), hepatorrhaphy and packing (5), packing followed by hepatectomy (2) and atriocaval shunt for direct repair (1). The survival rate for the packing group was higher than that of the direct repair group (75% versus 45%), but was not statistically significant (p = 0.352). Injury to the retrohepatic vena cava influenced the patient's survival significantly (p = 0.041). The overall survival was 58% (11/19). CONCLUSION: A well-defined operative strategy helps surgeons deal with the problem of blunt juxtahepatic venous injury, and its combination with multidisciplinary management will improve patient outcomes.     

Reductive transformation of hexahydro-1,3,5-trinitro-1,3,5-triazine, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, and methylenedinitramine with elemental iron

Reductive (pre)treatment with elemental iron is a potentially useful method for degrading nitramine explosives in water and soil. In the present study, we examined the kinetics, products, and mechanisms of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) degradation with elemental iron. Both RDX and HMX were transformed with iron to formaldehyde, NH4+, N2O, and soluble products. The yields of formaldehyde were relatively constant (71% +/- 5%), whereas the yields of NH4+ and N2O varied, depending on the nitramine and the mechanism. The reactions most likely were controlled by a surface process rather than by external mass transfer. Methylenedinitramine (MDNA) was an intermediate of both RDX and HMX and was transformed quantitatively to formaldehyde with iron. However, product distributions and kinetic modeling results suggest that MDNA represented a minor reaction path and accounted for only 30% of the RDX reacted and 14% of the formaldehyde produced. Additional experiments showed that RDX reduction with elemental iron could be mediated by graphite and Fe2+ sorbed to magnetite, as demonstrated previously for nitroaromatics and nitrate esters. Methylenedinitramine was degraded primarily through reduction in the presence of elemental iron, because its hydrolysis was slow compared to its reactions with elemental iron and surface-bound Fe2+. Our results show that in a cast iron-water system, RDX may be transformed via multiple mechanisms involving different reaction paths and reaction sites.     

热毒平抗中暑内毒素血症的作用研究

在干球温度 (4 2± 0 . 5 )℃、湿球温度 (3 5± 0. 5 )℃、相对湿度 60 %± 5 %的条件下建立中暑模型 ,应用热毒平、地塞米松等药物 ,观察动物的肛温上升速率、存活时间、 3h死亡率。结果热毒平组比地塞米松组、西黄芪胶组和高温中暑组动物的肛温上升速率慢 ,分别为 0 . 0 2 3℃ /min、 0 . 0 48℃ /min、 0. 0 3 0℃ /min、 0 . 0 43℃ /min (P <0 . 0 5 ) ;较其他三组动物的存活时间长 ,分别为 198 88min、 113 88min、 164 63min、 12 5 63min (P <0. 0 5 ) ;比其他三组动物的3h死亡率低 ,分别为 2 5 %、 10 0 %、 75 %、 75 % (P <0. 0 5 )。提示热毒平对中暑内毒素血症具有良好的预防效果。     

Immunophenotypic and genetic characterization of a CD8 positive mantle cell lymphoma in a patient with concomitant Mycosis fungoides

Mantle cell lymphoma (MCL) is immunophenotypically characterized by cell surface co-expression of CD19, CD20, CD5, IgM and FMC7. However, the concomitant presence of other antigens distinctive of a particular leukocyte subset, e.g. T-lymphocytes, is an exceptional finding in MCL. Here, the first case of a blastic MCL in leukaemic phase with aberrant expression of the T-cell associated antigen CD8 occurring in a patient with concomitant Mycosis fungoides is described. Comprehensive immunophenotypic analysis showed that the MCL cells expressed the typical B-lymphocytic markers, were CD5 and CD8 positive, but did not express other T-cell proteins, such as CD2, CD3, CD4, CD7, TCRalphabeta and TCRgammadelta. The MCL cells expressed both CD8alpha and CD8beta chains indicating cell surface presence of CD8alphabeta heterodimers. Intriguingly, expression of the cytotoxic enzymes perforin and granzyme A was detected by RT-PCR. Cytogenetic and molecular genetic analysis of the lymphoma cells confirmed cyclin D1 overexpression secondary to the t(11;14)(q13;32) chromosomal translocation. Furthermore, trisomy 11, trisomy 14 and extra copies of t(11;14) translocated chromosomes were detected in sub clones of the analyzed MCL cells. Clinically, an aggressive course of disease including cerebral lymphoma involvement was noted in the reported patient. Hence, systematic studies addressing the incidence, biology and clinical behavior of this form of MCL seem to be justified in future.