肺纤维化大鼠纤维连接蛋白的动态变化及秋水仙碱的抑制作用

动态观察博莱霉素致肺间质纤维化大鼠的支气管肺泡灌洗液中细胞总分数、肺泡巨噬细胞培养上清中纤维连接蛋白含量的变化及肺脏病理改变，并以秋水仙碱进行体内干预。结果：模型组在疾病早期的支气管肺泡灌洗液中细胞总数、中性粒细胞及肺泡巨噬细胞培养上清纤维连接蛋白含量明显增高；药物干预组支气管肺泡灌洗液的细胞总数，中性粒细胞及纤维连接蛋白含量较模型组明显降低。提示：秋水仙碱可能对纤维连接蛋白的形成产生影响。     

MTT方法测定培养细胞抗药水平的评价

用ＭＴＴ方法测定了多药抗药细胞ＭＣＦ－７Ａｄｒ及其敏感细胞ＭＣＦ－７ＷＴ对阿霉素、长春新碱、秋水仙碱的化学敏感性。ＭＣＦ－７Ａｄｒ与ＭＣＦ－７ＷＴ相比，对三种药物有明显的抗药性。维拉帕米可逆转ＭＣＦ－７Ａｄｒ对阿霉素的抗药性。随选择药物撤除时间的延长，ＭＣＦ－７Ａｄｒ的抗药水平逐渐下降。Ｓｏｕｔｈｅｒｎ杂交显示ＭＣＦ－７Ａｄｒ细胞有典型的ＭＤＲ１基因扩增现象。用ＭＴＴ方法测定Ｓｗｉｓｓ３Ｔ３细胞对阿霉素、长春新碱、秋水仙碱的化学敏感性，同时测定时各亚克隆株间差异较小，而分批测定时，不同批次相差很大。结果说明，ＭＴＴ方法能有效地检测出抗药细胞株的相对抗性；并提示，应在同时用完全相同的条件进行杀伤试验与ＭＴＴ测试，以避免批次间差异。     

Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair

Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate beta-lyase, the enzyme that bio-activates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephro-protection. These findings suggest that pre-placement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure.     

硫代秋水仙碱衍生物的合成和抗肿瘤活性

目的寻找高效低毒的秋水仙碱抗肿瘤衍生物。方法秋水仙碱首先被转化为硫代秋水仙碱，然后硫代秋水仙碱通过水解得到7-(N-脱乙酰基硫代秋水仙碱)，最后经胺的酰化得到目标化合物。用¹H NMR，IR，MS和HR-MS确证了这些衍生物的结构，MTT法评价了目标衍生物的细胞毒性；用对小鼠肝癌H₂₂和宫颈癌U₁₄的抑制率评价了衍生物的体内抗肿瘤活性。结果合成了12个硫代秋水仙碱新衍生物。结论尽管一些硫代秋水仙碱衍生物的体外细胞毒性强于秋水仙碱，然而小鼠体内抑瘤活性却较低。     

丹参多酚酸盐对肝硬化门静脉高压抑制作用的研究

[目的]研究丹参多酚酸盐对大鼠肝硬化门静脉高压的抑制作用。[方法]采用腹腔注射二甲基亚硝胺(DMN),每周前3天注射,共4周的方法制备肝硬化门静脉高压大鼠模型,设正常对照组、模型组(生理盐水)、丹参多酚酸盐[12、24、48 mg/(kg·d)]治疗组和秋水仙碱[0.1 mg/(kg·d)]治疗组,每组20只,疗程6周。测定血清中转氨酶、总胆红素(TBIL)、肝纤四项[(Ⅳ型胶原(C-Ⅳ)、Ⅲ型前胶原(PC-Ⅲ)、透明质酸酶(HA)、层粘连蛋白(LN)]含量和肝脏中羟脯氨酸(HYP)水平,通过苏木精-伊红(HE)染色观察肝脏组织病变,记录门静脉压(PVP)、门静脉血流量(PVF)、平均动脉压(MAP)和心率(HR);测定肝脏中丙二醛(MDA)含量和抗氧化酶活性。[结果]经丹参多酚酸盐[24、48 mg/(kg·d)]组治疗能够显著降低肝硬化门静脉高压大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、TBIL、Ⅳ型胶原(C-Ⅳ)、Ⅲ型前胶原(PC-Ⅲ)、透明质酸酶(HA)、HYP含量(P0.05或P0.01);降低PVP和PVF(P0.05);提高肝脏中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性并降低MDA含量(P0.05或P0.01)。经丹参多酚酸盐48 mg/(kg·d)组治疗能够显著降低LN含量、提高MAP、降低HR(P0.05或P0.01)。经丹参多酚酸盐治疗能够明显改善肝硬化门静脉高压大鼠肝脏组织病变,以[48 mg/(kg·d)]组效果最为显著。[结论]丹参多酚酸盐对大鼠肝纤维化门静脉高压具有一定的抑制作用,机制可能与丹参多酚酸盐能够降低氧化应激损伤。     

Role of cholinoceptors recycling in short-term potentiation of cholinosensitivity of command neurons in edible snail

Exocytosis inhibitor Exo 1, dynamin inhibitory peptide (inhibitor of endocytosis), and colchicine disturb short-term potentiation of cholinosensitivity of defensive behavior command neurons in edible snail induced by rhythmic electrical orthodromic stimulation. We hypothesize that the short-term potentiation of cholinosensitivity in the extra-synaptic membrane develops due to incorporation of extra cholinoceptors into neuron plasmalemma as a result of enhanced recycling of the internalized cholinoceptors with participation of microtubules. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 9, pp. 247–250, September, 2007     

Nootropic activity of acetaminophen against colchicine induced cognitive impairment in rats

Alzheimer's disease is a devastating neurodegenerative disorder, the most common among the dementing illnesses. Acetaminophen has gaining importance in neurodegenerative diseases by attenuating the dopaminergic neurodegeneration in Caenorhabditis elegans model, decreasing the chemokines and the cytokines and increasing the anti apoptotic protein such as Bcl-2 in neuronal cell culture. The low concentration acetaminophen improved the facilitation to find the hidden platform in Morris Water Maze Test. Also some data suggest that acetaminophen could contribute in neurodegeneration. The present study was aimed to evaluate the effect of acetaminophen against colchicine induced cognitive impairment and oxidative stress in wistar rats. The cognitive learning and memory behaviour was assessed using step through passive avoidance paradigm and acetylcholine esterase activity. The parameters of oxidative stress were assessed by measuring the malondialdehyde, reduced glutathione and catalase levels in the whole brain homogenates. There was a significant memory improvement in the rats received acetaminophen treatment and it has also decreased the acetylcholine esterase enzyme level, confirming its nootropic activity. Acetaminophen neither increases nor decreases the reduced glutathione and catalase in the whole brain homogenates, showing that acetaminophen is devoid of any adverse effect on brain antioxidant defense system.     

The most commonly altered type of Peyronie's disease deformity under oral colchicine treatment is lateral curvature that mostly shifts to the dorsal side

The aim of the present study was to evaluate changes in clinical characteristics of Peyronie's disease (PD) patients under oral colchicine treatment in comparison with the initial clinical evaluation with a special emphasis on patients with altered deformity after treatment. A total of 118 patients under oral treatment with colchicine for at least 3 months in the acute phase of PD were retrospectively evaluated with combined infection and stimulation test. PD patients were followed up in four groups according to the clinical course of the deformity: improved, remained unchanged, deteriorated deformities or altered localisation of the deformity. Among 116 patients who completed the treatment, penile curvatures improved in 27.6% (n = 32), remained unchanged in 39.7% (n = 46) and deteriorated in 12.1% (n = 14) of the patients after a follow-up of 8.6 ± 3.2 (6-17) months, while localisation of the deformities changed in 20.7% (n = 24) of the patients. In this group, the initial side of the deformities were lateral, ventral, ventrolateral in 41.6% (n = 10), 29.1% (n = 7) and 8.3% (n = 2) of the patients and of hourglass and notching type (n = 4, 16.6%) respectively. Six (60%) patients with lateral, five (71.4%) with ventral curvatures completed their follow-up period with dorsal curvatures. In conclusion, lateral curvature is the most commonly altered deformity that mostly shifts to the dorsal sise of the penis after colchicine therapy.     

Colchicine intoxication and infection risk: a case report

Colchicine is widely used, primarily for the treatment of gouty arthritis and familial Mediterranean fever. Colchicine intoxication is a rare but potentially life-threatening event. Herein, we reported a 26-year-old woman who presented to the emergency department after ingesting 27·5 mg of colchicine in a suicide attempt. She exhibited signs typical of colchicine-poisoning and developed infectious complications but with subsequent complete recovery. This paper discusses the role of colchicine poisoning in increasing susceptibility to infections. This aspect is usually under-appreciated in the clinical picture of colchicine overdose.     

Vitamin D status in patients with Behcet's Disease

OBJECTIVES:

This study investigated the serum 25-hydroxyvitamin D levels of patients with Behcet''s Disease.

DESIGN AND METHODS:

Thirty-two patients with Behcet''s Disease and 31 matched healthy controls were enrolled in this study. The erythrocyte sedimentation rate (ESR) and the levels of C-reactive protein (CRP), serum 25-hydroxyvitamin D, calcium (Ca), phosphate (P), and total alkaline phosphatase (ALP) were measured in both groups.

RESULTS:

There were no significant differences between the two groups regarding demographic data. The serum 25-hydroxyvitamin D levels of patients and controls were 13.76 (range: 4.00-35.79) and 18.97 (range: 12.05-36.94) ng/ml, respectively. In patients with Behcet''s Disease, 25-hydroxyvitamin D values were significantly lower than those of the healthy controls (p<0.001). Serum Ca, P, and ALP levels were similar in both groups. Serum ESR and CRP levels were significantly higher in patients than controls (p<0.05). There was no correlation between 25-hydroxyvitamin D levels and age, body mass index (BMI), disease duration, ESR, or CRP levels. Multivariate regression analysis parameters showed that smoking, alcohol intake, and use of colchicine were the main predictors of 25-hydroxyvitamin D levels. Of the parameters studied, the largest impact was due to colchicine therapy (p<0.001). We did not find a significant relationship between the use of corticosteroids and 25-hydroxyvitamin D levels.

CONCLUSION:

Our results suggest that serum 25-hydroxyvitamin D levels are decreased in patients with Behcet''s Disease. Smoking, alcohol intake, and use of colchicine appear to affect vitamin D levels.