Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels

Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K⁺ current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that are characterized by a high expression of Kv1.3 and Kv1.3 antagonists ameliorate autoimmune disorders in vivo. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in patients who suffer from painful autoimmune diseases such as rheumatoid arthritis. In this study, we show that diclofenac impairs immune response via a mechanism that involves Kv1.3. While diclofenac inhibited Kv1.3 expression in activated macrophages and T-lymphocytes, Kv1.5 remained unaffected. Diclofenac also decreased iNOS levels in Raw 264.7 cells, impairing their activation in response to lipopolysaccharide (LPS). LPS-induced macrophage migration and IL-2 production in stimulated Jurkat T-cells were also blocked by pharmacological doses of diclofenac. These effects were mimicked by Margatoxin, a specific Kv1.3 inhibitor, and Charybdotoxin, which blocks both Kv1.3 and Ca²⁺-activated K⁺ channels (K_Ca3.1). Because Kv1.3 is a very good target for autoimmune therapies, the effects of diclofenac on Kv1.3 are of high pharmacological relevance.     

中西医结合治疗特发性膜性肾病临床观察

目的 :观察中西医结合治疗特发性膜性肾病临床疗效。方法 :对 6 8例特发性膜性肾病随机分为对照组 32例 ,治疗组 36例 ;对照组单纯用强的松和环磷酰胺、潘生丁、洛丁新 ,治疗组在用上述西药同时辨证加用中药治疗 ,观察 3年～ 6年。结果 :对照组完全缓解率为 2 8.1% ,总缓解率为 6 5 .6 % ;治疗组完全缓解率为 5 5 .6 % ,总缓解率为 86 .2 %。治疗组完全缓解率和总缓解率明显优于对照组 ,两组比较P <0 .0 5 ,具有显著性差异。结论 :中西医结合是治疗膜性肾病的有效方法。     

环磷酰胺冲击治疗狼疮肾炎的临床研究

目的通过临床对比研究，探讨应用环磷-酰胺冲击治疗（IV－CTX）狼疮肾炎（LN）的最佳方案。方法将92例LN患者随机分成3组：A组，IV－CTX每2周1次，每次（8～12）mg／kg，连用2天，B组，IV－CTX每月1次，每次（0．5～1．0）g／m2；C组，IV－CTX每3个月1次，每次（0．5～1．0）g／m2。3组均同时口服波尼松。结果A组起效时间显著比B组与C组快；病情缓解率A组也显著高于B组及C组（P＜0．01）；病情活动性积分下降至25％、50％和75％时，3组CTX累积量无显著差异（P＞0．05）；3组间不良反应及其发生率无显著统计学差异（P＞0．05）。结论IV－CTX治疗LN应根据狼疮活动程度选择。在急重症LN，应用A组2周1次方案有利于及时控制狼疮活动，提高疗效，保护肾功能；在LN病情基本控制后，改用B组每月1次方案可以巩固疗效；在LN病情完全控制后，应用C组3个月1次方案可以预防复发。     

大剂量环磷酰胺冲击疗法治疗难治性天疱疮的护理2例

我科 2 0 0 1年收治了 2例病情严重、治疗困难的天疱疮患者 ,常规治疗无效 ,采用特大剂量ＣＴＸ治疗并精心护理 ,使病情得以控制 ,报告如下。1　病例介绍例 1:患者 ,男 ,6 0岁 ,干部。因全身皮肤反复发生水疱、糜烂 5ａ,于 2 0 0 1年 5月第 6次入院。患者于 1995年开始 ,反复全身出现水疱、糜烂及口腔溃疡 ,1996年 8月第 1次入院 ,皮损病理 :表皮内疱 ,棘细胞松解 ,棘细胞间ＩｇＧ、Ｃ3 呈网状沉积。诊断 :寻常型天疱疮。经激素及ＣＴＸ等治疗 ,病情缓解 ,皮损全部消退出院。 1998年底喝酒后病情复发而再次住院 ,经 3个疗程小剂量激素冲击并…     

CTX-M-14 type β-Lactamase producing Escherichia coli isolated from hospitalized patients in Tunisia

Escherichia coli (E.coli) with a CTX-M resistance phenotype was selected from hospitalized patients in a university Hospital of Tunisia between January 2010 and June 2010. PCR analysis and sequencing demonstrated that it harboured CTX-M-14 β-lactamase. Characterization of the regions surrounding the bla(CTX-M-14) showed the ISEcp1 elements located in the upstream region of the bla gene. PFGE and multilocus sequence typing revealed two different types which corresponds to sequence types ST38 complex and ST131. These results reinforce the potential for spreading of this gene among E. coli clinical strains in the coming years in Tunisia.     

鸡血藤提取物对环磷酰胺致白细胞低下大鼠的影响

目的利用环磷酰胺(CTX)致白细胞低下大鼠模型研究鸡血藤提取物的升白细胞作用,发现其升白细胞作用的有效部位。方法采用CTX(100 mg/kg)单次sc的方法制备大鼠白细胞低下模型,给药后第7、9、11天采集大鼠的血液,测定白细胞总数及分类,并进行统计分析。结果鸡血藤提取物A(50%乙醇提取,为总提取物)、B(50%乙醇提取-水洗脱)、C(50%乙醇提取-25%乙醇洗脱)组均未见明显升白细胞作用,而鸡血藤提取物D(50%乙醇提取-70%乙醇洗脱,总黄酮量大于55%)和阳性药利可君均具有明显的升白细胞作用,且鸡血藤提取物D的升白细胞作用具有量效关系,优于阳性药利可君。结论鸡血藤提取物D可能是鸡血藤升白细胞作用的有效部位,推测其升白细胞作用的有效物质是总黄酮。     

Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses

The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer.     

Dietary coral calcium and zeolite protects bone in a mouse model for postmenopausal bone loss

In patients diagnosed with osteoporosis, calcium is lost from bones making them weaker and easily susceptible to fractures. Supplementation of calcium is highly recommended for such conditions. However, the source of calcium plays an important role in the amount of calcium that is assimilated into bone. We hypothesize that naturally occurring coral calcium and zeolite may prevent ovariectomy-induced bone loss. We have measured bone loss in ovariectomized mice supplemented with coral calcium and Zeolite. Female C57BL/6 mice were either sham-operated or ovariectomized and fed diets containing coral calcium or zeolite for 6 months. Serum was analyzed for bone biochemical markers and cytokines. Bones were analyzed using dual x-ray absorbtiometry, peripheral quantitative computed tomography, and micro–computed tomography densitometry. In the distal femoral metaphysis, total bone and cortical bone mass was restored and the endocortical surface was significantly decreased in coral calcium and zeolite fed ovariectomized (OVX) mice. Trabecular number and the ratio of bone volume to total volume was higher in OVX mice after coral calcium and zeolite feeding, while trabecular separation decreased in the different treatment OVX groups. Coral calcium protected bone to a lesser extent in the proximal tibia and lumbar vertebrae. Overall, coral calcium and zeolite may protect postmenopausal bone loss.     

血小板第4因子造血保护作用的实验研究

目的 :研究血小板第 4因子 (PF4)对环磷酰胺 (CTX)处理小鼠体内造血系统的保护作用。方法 :实验鼠用PF4注射 2次 ,间隔 6h ,第二次注射后 2 0h给予CTX 2 0 0mg·kg- 1 。动态观察小鼠外周血白细胞数以及不同时期外周血T细胞亚群 ,骨髓粒-巨噬系集落形成单位 (CFU -GM)、细胞周期和小鼠脾脏、胸腺的变化。结果 :PF4能增加CTX处理小鼠骨髓CFU -GM的产率 ,加速体内CFU -GM的恢复 ;短时增加CTX处理小鼠骨髓G0 /G1 期细胞 ,减少骨髓细胞的坏死和凋亡 ;增加胸体比和脾体比。但是PF4对小鼠外周血白细胞数和T细胞亚群未见明显影响。结论 :PF4能保护小鼠骨髓及胸腺、脾脏等器官组织免受CTX损伤 ,增加骨髓CFU -GM的形成能力