Spared place and object-place learning but limited spatial working memory capacity in rats with selective lesions of the dentate gyrus

We studied the cognitive performance of rats with colchicine-induced lesions of the hippocampal dentate gyrus (DG) on a range of spatial, non-spatial and mixed spatial/procedural tasks. Rats were assigned to three experimental groups receiving large colchicine lesions (7 microg per hippocampus), small colchicine lesions (1.75 microg per hippocampus) or sham lesions. Stereological estimates of cell density indicated that the colchicine treatments induced dose-dependent damage to the DG, while sparing in large part other hippocampal subfields. Remarkably, the behavioural results showed that the colchicine lesions did not affect the performance of rats in an object discrimination task, in an object-place associative task in which a familiar object was displaced from a given position nor in a spontaneous spatial discrimination task performed in the T-maze. However, rats in both lesion groups were severely impaired in a reinforced non-matching-to-position working memory task conducted in the T-maze. Importantly, performance in the working memory task correlated strongly with cell density in the DG but not with cell density in the CA1 and CA3 areas. Only rats with large-lesions showed a transient deficit in a reinforced rule-based conditional discrimination task. These data demonstrated that rats with selective lesions of the DG readily acquire and retain neural representations relative to objects and places but are specifically impaired in their ability to update rapidly and flexibly spatial information that is essential to guide goal-directed actions.     

A case of Riedel’s thyroiditis with pleural and pericardial effusions

Riedel’s thyroiditis (RT) is a rare type of chronic thyroiditis of unproven etiology and definite treatment. It can be associated with retroperitoneal, mediastinal, orbital, and hepatic fibrosis. Symptoms arise mainly due to compression of neighboring structures. Surgery is usually required for a definite diagnosis and decompression to relieve the symptoms. Glucocorticoids and tamoxifen are commonly used agents for the pharmacotherapy. We hereby describe the development of pleural and pericardial effusions during the clinical course of an RT case. A 39-year-old woman suffering from neck compression symptoms was admitted to the hospital. After a decompression isthmectomy, RT was diagnosed. She responded well to glucocorticoid therapy after surgery. However, symptoms reoccurred shortly after glucocorticoid withdrawal and the disease process extended to the mediastinum. Tamoxifen was started and the neck and mediastinal mass regressed and her symptoms disappeared considerably for more than 6 months. However, she was readmitted with severe dyspnea and chest pain. Further investigation revealed an exudative pleural and pericardial effusion and mediastinal enlargement. A thorough evaluation of the patient’s effusions did not disclose any specific etiological insult. The patient was symptom-free with a considerable reduction of the soft tissue mass and no effusions, and treated successfully with colchicine, azathioprine, and glucocorticoids. To the best of our knowledge, this is the first case reported in the literature as an RT presenting with pleuropericardial effusions.     

肝细胞癌细胞粘弹性的改变及细胞骨架干扰剂的影响

目的 从细胞骨架角度探讨肝癌细胞粘弹性改变的基础，及细胞骨架结构干扰剂对其改变的影响方法采用微管吸吮技术测定正常肝细胞的粘弹性，三参数标准线性固体模型拟合实验结果。结果 肝癌细胞的弹性系数较肝细胞增高，秋水仙素、长春花碱使癌细胞粘弹性系数与肝细胞相比呈现不同的效应方式和强度，细胞松驰素Ｄ则使２种细胞弹性系数均呈现相似的显著下降趋势。结论 细胞骨架结构的完整性是维持肝细胞和肝癌细胞粘弹性及被动变形机     

Silica-Polyethylene Glycol Matrix Synthesis by Sol-Gel Method and Evaluation for Diclofenac Diethyloammonium Release

Modified silica-polyethylene glycol xerogels were prepared by the sol-gel method to explore the possibilities of using these polymers as drug delivery systems. The synthesis was performed at room temperature and under atmospheric pressure using tetraethylorthosilicate (TEOS) as a precursor, low-molecular polyethylene-glycol (600) as a modifier, and acetic acid as a catalyst. The composition in a mole ratio of the initial sols corresponds to TEOS:H₂O:EtOH:CH₃COOH:PEG = 1:4:6:0.005:0.147. Diclofenac diethyloammonium was used as a model drug and encapsulated in predoping sol-gel process. After 5 days of gelation time of matrices at room temperature two different forms of xerogels were obtained: monolithic form of pellet and cracked, irregular-shaped of particles. The rate of release from the both forms of xerogels was controlled by the rate of diffusion of the drug through the pores. The dissolution testing for the loaded irregular-shaped xerogels showed an initial burst release followed by sustained release. The degradation of the PEG/silica xerogels followed a zero-order kinetics.     

Colchicine treatment in children with familial Mediterranean fever

Prophylactic colchicine therapy has been shown to be a safe and effective method of eliminating the attacks and preventing the development of amyloidosis in patients with familial Mediterranean fever (FMF). However, information about effective dosages that control FMF attacks and prevent amyloidosis in childhood is not available. The aim of this study is to determine the effective colchicine dose for children in terms of body weight and surface area. Sixty-two (34 male, 28 female) children with FMF were selected and colchicine treatment was initiated by giving 0.5–1 mg/day to each patient. The dose was gradually increased up to a maximum 2 mg/day in unresponsive patients; mean duration of therapy was 45.6 ± 35.5 months. When the optimal effective dosage (i.e. the one that reduced the frequency of attacks and ESR, CRP and fibrinogen levels during the attack-free period) was achieved, the optimal effective dose was calculated according to the body weight and body surface area for each patient. Based on these values mean colchicine dose was computed for the study group and values for different age groups were evaluated. Mean colchicine doses according to the body weight and surface area of the whole group were found to be 0.03 ± 0.02 mg/kg/day and 1.16 ± 0.45 mg/m²/day, respectively. It was shown that children less than 5 years of age might need colchicine doses as high as 0.07 mg/kg/day or 1.9 mg/m²/day. These dosages are approximately 2.5–3 times more than the mean colchicine dose for children aged 16–20 years. These results clearly show that small children need higher doses of colchicine in order to control their attacks. Thus, we conclude that colchicine, when given according to body weight or body surface area, would be more effective in childhood.     

Enhancement of Transdermal Iontophoretic Delivery of a Liposomal Formulation of Colchicine by Electroporation

Iontophoresis of colchicine solution through electroporated skin showed maximum enhancement as compared to iontophoresis and electroporation alone. Encapsulation of colchicine in positively charged liposomes further augmented the delivery,with the amount of drug in the receptor after 24 h being 1348 342 mug/cm2 when iontophoresis was performed through electroporated skin as compared to 666 38mug/cm2 when it was performed through nonelectroporated skin and 41 18mug/cm2 when only electroporation was performed. The impedance of the skin was observed to drop sharply due to electroporation, with a postpulse recovery of about 30% over 24h. Also the total amount transported was compared to the total charge delivered in the case of each of the protocols. Hence this serves as initial evidence for potential of charged liposomes for the enhanced transdermal delivery of nonionized or neutral drugs using a combination of electroporation and iontophoresis.     

秋水仙碱对急性脑梗死预后的影响

目的　探讨秋水仙碱对急性脑梗死患者预后的影响。方法　将60例急性脑梗死患者随机分为两组。对照组30例,接受急性脑梗死的基本治疗;治疗组30例,接受秋水仙碱1.5 mg/d和基本治疗,共14 d。两组分别于入院后和发病后1个月测量血白细胞计数、纤维蛋白原和血沉; 同时测量脑梗死灶体积变化、神经功能评分(MESS)及日常生活活动(ADL)量表记分的变化, 并将两组进行比较。结果　(1)秋水仙碱治疗后脑梗死体积较治疗前明显缩小(P<0.01); (2)血清纤维蛋白原水平、白细胞计数及血沉治疗后下降较对照组差异有显著意义(P<0.01); (3)神经功能缺损评分显著低于对照组(P<0.001); 而日常生活活动量表评分显著高于对照组(P<0 .001)。结论　秋水仙碱能缩小脑梗死体积、减轻神经功能缺损, 改善急性脑梗死患者的预后。     

秋水仙碱对单核细胞产生细胞因子的影响

微管聚合抑制剂秋水仙碱（Ｃｏｌ，１０－５ｍｏｌ／Ｌ）可抑制ＬＰＳ刺激人单核细胞分泌１７ｋＤＴＮＦ－α及膜相关２６ｋＤＴＮＦ－α；与之相反，它却可促进ＩＬ－１β（多为分泌型）的分泌，而对ＩＬ－１α（多为膜相关型）则表现为抑制作用。对于ＩＬ－６，Ｃｏｌ无明显影响。Ｎｏｒｔｈｅｒｎ分析显示，Ｃｏｌ对ＴＮＦ－α及ＩＬ－１βｍＲＮＡ产生亦表现为相反作用，即对前者抑制，对后者促进作用。     

On the changes of the time course of the end-plate current during repetitive stimulation

Summary In a previous study it was observed that prolonged repetitive stimulation (10.s^–1) markedly lengthened the time course of the end-plate current. In order to investigate whether this effect could be due to a more dispersed release of the mediator or to a decreased clearance of the mediator from the synaptic cleft, the rise time of the end-plate current and of the miniature end-plate current were analyzed. The results show that presynaptic factors may be involved.     

Mediterranean fever gene variants and colchicine therapy in periodic fever,aphthous stomatitis pharyngitis,adenitis syndrome in a Mediterranean region

Objectives: Periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome is characterized by recurrent episodes of fever. Attenuated disease severity was considered in patients with Mediterranean fever (MEFV) gene variations. Corticosteroids are highly effective in controlling the symptoms but usually cause more frequent episodes. Frequent fever episodes either initiated after the steroid therapy or as an initial disease characteristics are the most challenging feature.

Methods: Sixty-seven patients were prospectively followed from September 2015 to January 2018. MEFV variants were searched in all patients. Colchicine therapy was initiated in patients with MEFV variants and with shortened intervals after the initiation of steroid therapy.

Results: Heterozygous MEFV gene variants were detected in 23 patients (34.3%). Higher exon 10 allel frequencies were found in patients with frequent fever episodes. Among 26 patients with increased episodes, colchicine treatment decreased the number of the episodes in 8 of 10 (80%) and 4 of 16 (25%) patients with and without variants, respectively (p = 0.022). Fever duration decreased (3.26 ± 1.38 vs. 1.57 ± 0.57 days, p < 0.001) at the third month of therapy in variant(+) patients.

Conclusion: In variant positive patients colchicine prophylaxis reduced the duration of attacks at the third months of therapy. Shortened intervals due to steroid therapy were increased at the sixth months of colchicine therapy.