实验家兔莱姆病血液学研究

本实验复制了莱姆病实验家兔模型，对血液生化23项进行了动态观察。结果表明，血液中谷丙转氨酶、γ-谷氨酰转肽酶、乳酸脱氢酶、谷草转氨酶、β-羟丁酸脱氢酶、磷酸肌酸激酶、胆固醇、尿素氮随病情加重而升高。葡萄糖、尿酸、磷随病情加重而减低。     

Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice

The objective of this study was to determine whether the development of tolerance to CP 55,940, a potent cannabinoid agonist, was due to changes in the receptor or second messenger system. ICR mice treated with CP 55,940 (2 mg/kg) twice a day for 6 and one-half days developed a high degree of tolerance to the pharmacological effects of CP 55,940. The ability of CP 55,940 to produce motor hypoactivity, hypothermia and immobility was reduced 163-, 97- and 19-fold, respectively. Evaluation of 3H-CP 55,940 binding to rat brain membranes indicated no difference in receptor affinity between the vehicle- and CP 55,940-treated animals. However, these binding studies revealed a 50% decrease in receptor number in the cerebellum of the CP 55,940-tolerant mice. Although cAMP is generally considered to be the second messenger for cannabinoid receptors, little difference was observed in the inhibitory effects of CP 55,940 on adenylyl cyclase activity in cerebellum between vehicle and drug-treated mice. However, there was an increase in receptor mRNA which suggests a compensation for receptor loss. There are several possible explanations for these results. There may be sufficient spare receptors such that CP 55,940-tolerant mice are capable of producing a maximal effect on the second messenger system. On the other hand, one could conclude that cannabinoid receptor down-regulation does not account for the development of tolerance to all of the effects of CP 55,940 in mice.     

雷公藤生物碱的分离鉴定

我们从雷公藤（ＴｒｉｐｔｅｒｙｇｉｕｍＷｉｌｆｏｒｄｉｉＨｏｏｋ．ｆ．）中按常法分离得到总碱后经ＨＰＬＣ分析出现８个峰，经硅胶柱层析及硅胶ＲＰ－１８反相中压柱层析分离得到５个生物碱，由化学方法和光谱分析证明为雷公藤吉碱（Ｗｉｌｆｏｒｇｉｎｅ２０）．雷公藤次碱（Ｗｉｌｆｏｒｉｎｅ２１），雷公藤春碱（Ｗｉｌｆｏｒｔｒｉｎｅ２２），雷公藤碱戊（Ｗｉｌｆｏｒｉｄｉｎｅ２３），呋喃南蛇碱（Ｃｅｌａｆｕｒｉｎｅ１６）。ＨＰＬＣ分析指出含量最高为雷公藤吉碱，其次为呋喃南蛇碱。     

In vivo 23Na NMR studies of myotonic dystrophy

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. ²³Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the ²³Na and ¹H water signals, and the fast transverse relaxation time, T₂₁, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that ²³Na NMR enables the quantitation of myotonic dystrophy progression.     

Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis

Summary Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p=0.0093) and in sCD14 (p=0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p=0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain

Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.     

IL-12家族新成员及其在免疫应答中的重要调节作用

白细胞介素-12(Interleukin-12, IL-12)家族成员IL-12、 IL-23、 IL-27三者及其各自受体在结构上的相似性, 使得它们在发挥调节NK细胞活性、 T细胞增殖和细胞因子产生以及抗体类别转换等方面的功能相互重叠但又不完全相同.而2007年发现的该家族的另一新成员IL-35, 结构上虽与其他3个成员同源, 但却具有独特的生物学功能, 是一种主要由调节性T细胞(Treg)分泌的抑制性细胞因子.IL-12家族各成员以及同其他细胞因子之间存在着相互协同、相互拮抗的网络, 不仅在细胞内感染及炎症过程中起着重要的调节作用, 而且与银屑病、多发性硬化症、 Crohn' s病等多种临床疾病的发病密切相关.IL-12家族相关生物制品在自身免疫性疾病、感染性疾病以及肿瘤的治疗中有着广阔的应用前景.