Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection

BACKGROUND: The concentration of rhinovirus in nasal wash specimens from infected volunteers peaks at 48-72 h after inoculation. The volume of expelled nasal fluid peaks at the same time, raising the question of whether the viral concentration in nasal wash reflects viral replication in nasal cells or merely the production of an increased volume of nasal fluid during a cold. OBJECTIVES: To determine the amount of rhinovirus in nasal lining fluid during colds before the nasal fluid has been diluted in a nasal wash. STUDY DESIGN: Rhinovirus titers were determined in nasal wash specimens collected daily for five days from 14 subjects with type16 rhinovirus infection. The urea concentration in nasal lining fluid equals that in blood. By determining the urea concentration in a nasal wash and comparing it to the urea concentration in blood from the same subject, it was possible to determine the amount of dilution of the nasal lining fluid. The dilution factor (reciprocal of the dilution) was then used to calculate the viral concentration in undiluted nasal lining fluid. RESULTS: The dilution factor in 70 nasal washes varied from 5 to 64. The viral GMTs (+S.E.) in nasal washes were 1.79 (+0.3) TCID(50)/ml at 24 h, 3.11 (+0.15) at 48 h, and 2.61 (+0.3) at 72 h. The viral GMTs in nasal lining fluid, based on urea adjusted values, paralleled those in nasal washes but were approximately one log higher. Virus concentrations returned to near baseline values by day 5. CONCLUSIONS: The temporal pattern of rhinovirus shedding observed in nasal wash specimens, with a peak in virus concentration at 48-72 h after infection, is a true indication of virus production in nasal cells and not an artifact of the increased amount of nasal fluid produced during the early phase of a cold.     

Isolation of rhinoviruses and coronaviruses from 38 colds in adults

Nasal washings were collected from 27 normal adults during 38 naturally acquired colds. The washings were exhaustively tested using tissue cultures, organ cultures and electron microscopy. Washings yielding no identifiable agent were inoculated into human volunteers, and further specimens obtained from the latter were examined by the same techniques in vitro. Viruses were identified in association with 25 of the original 38 colds (65.7%). Fifteen were rhinoviruses (39.5%), seven coronaviruses (18.4%), two were para-influenza viruses, and one was influenza virus. Use of organ cultures and of volunteers significantly increased the isolation rate. No agent was cultivated from the remaining 13 specimens, although tests in volunteers showed that cold-producing agents were present in five of them (13%). Three specimens gave doubtful results in volunteers, and five others, all collected within a period of six weeks in December and January, apparently contained no infectious agent.     

肩痛颗粒治疗肩周炎的临床观察

目的:初步观察和评价肩痛颗粒治疗肩痹(肩周炎)属风寒湿痹证者的疗效和安全性。方法:采用随机双盲、双模拟、平行阳性药对照的临床试验方法,将72例肩周炎(风寒湿痹证)患者,随机分为试验组(肩痛颗粒组)和对照组(祛痹肩安丸组),两组每次服用颗粒剂和丸剂各1袋,一日3次,疗程为4周。按照症状、体征分级量化标准,对治疗前及用药后每周进行疗效评价;并对患者进行用药前后的三大常规、心、肝、肾功能等安全性检查,观察以上安全性指标的变化。结果:疗效性结果:肩痛颗粒组的愈显率为29.63%,总有效率为92.59%;而祛痹肩安丸组分别为16.67%和83.33%。两组差别无统计学。每周证候总积分:试验组患者用药后21、28d中医证候总积分下降值和下降率均高于对照组,但差别无统计学意义。安全性结果:治疗前后患者的指标差异值无临床意义,未观察到药物引起的不良反应和不良事件。结论:肩痛颗粒在目前的口服剂量疗程范围内,治疗证属风寒湿痹的肩周炎疗效确切,安全,无毒副作用,是一种治疗肩周炎安全、有效的中药新药。     

温肺散寒化痰定喘法治疗小儿寒性哮喘临床研究

目的：探讨温肺散寒化痰定喘法治疗小儿寒性哮喘的临床疗效。方法：将254例小儿患者随机分为两组,治疗组130例,采用温肺散寒化痰定喘法治疗,方用小青龙汤合三子养亲汤（方药组成：麻黄、桂枝、细辛、干姜、半夏、五味子、白芍、白芥子、紫苏子、莱菔子）治疗;对照组124例,采用西药抗生素配合口服氨茶碱、酮替酚及特布他林气雾吸入,均以7d为1个疗程。结果：治疗组有效率89．23％,对照组有效率79．03％,经χ2检验,两组差异有统计学意义（P〈0．05）。结论：温肺散寒化痰定喘法治疗小儿寒性哮喘有良好效果。     

冷适应过程中大鼠脑垂体、下丘脑和血浆生物活性肽的变化及其对免疫功能的影响

我们采用RP-HPLC方法研究了SD纯系雄性大鼠冷适应期间脑垂体(P)、下丘脑(HT)和血浆(BP)生物活性肽变化。冷适应期间P、HT和BP肽类(MW≤30000)RP-HPLC图谱均出现一些新的肽洗脱峰。而且,所有这些肽类都能增强淋巴细胞(LC)转化活性。在P和HT肽类刺激下,脾LC[~3H]-TdR参入分别增加725 cpm(P<0.01)和1274 cpm(P<0.001)。将这些肽类进一步经Sep-Pack C_(18)柱纯化后仍分别增加[~3H]-TdR参入cpm值597(P<0.05)和333。这些结果表明了免疫系统(ImS)与神经内分泌系统(NES)双向调节环路的一个方面:NES作用于ImS。     

不同刺激量针刺关元穴对寒凝类痛经模型大鼠的影响

目的：观察不同的针刺刺激量施于关元穴对寒凝类痛经模型大鼠子宫组织中收缩素受体（ OTR）及肌球蛋白轻链激酶（ MLCK）含量的影响。方法将处于动情间期3月龄的SD雌性大鼠32只,随机分为盐水组、寒凝类痛经模型组24只,造模成功后将寒凝类痛经模型组又分为模型组、刺激量A组和刺激量B组,每组8只。除盐水组外,模型组、刺激量A组和刺激量B组均采用全身冷冻法结合苯甲酸雌二醇注射法造模。盐水组和模型组不予针刺,刺激量A组予以粗针、深刺、行手法;刺激量B组予以细针、浅刺、不施手法。采用荧光定量PCR方法检测大鼠子宫组织中缩宫素受体（ OTR）的含量。采用ELISA（酶联免疫法）测量大鼠子宫组织中MLCK的含量。结果与盐水组比较,模型组的子宫收缩波个数、波峰峰值、活动度及MLCK水平均升高（ P﹤0.01）;与模型组比较,刺激量A组的子宫收缩波个数明显减少（ P﹤0.05）、MLCK含量明显降低（ P﹤0.01）,刺激量B组的OTR mRNA相对表达量降低（ P﹤0.05）;与刺激量A组比较,刺激量B组收缩波个数增多（ P﹤0.05）、OTR mRNA相对表达量降低（ P﹤0.01）。结论不同刺激量针刺关元穴对寒凝类痛经模型大鼠的效应有所不同,粗针、深刺、行手法的效应较强于细针、浅刺、不行手法的针刺效应,提示针刺的刺激量也是决定针刺疗效的因素之一。     

Static cold storage preservation of ischemically damaged kidneys. a comparison between IGL-1 and UW solution.

Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.     

Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

BACKGROUND: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. METHODS: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. RESULTS: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. CONCLUSION: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.