海蓝组织细胞增生症临床及遗传方式的探讨

本文通过海蓝组织细胞(SBH)增生症一个家系的调查,发现6位患者。对 SBH 进行了细胞化学染色分析,还进行了光镜、位相显微镜荧光显微镜、透射及扫描电镜观察.认为 SBH 增生症的临床表现由 SBH 广泛全身浸润引起,并提出应与反应性 SBH 增生症鉴别.本家系遗传方式为常染色体显性遗传,和其它学者报告不同.     

Effects of a single or repeated administration of the benzodiazepine inverse agonist FG7142 on behaviour and cortical adrenoceptor binding in the rat

We have reported previously an increase in the number of -adrenoceptors in mouse cerebral cortex 7 days after kindling of seizures by repeated once-daily administration of the benzodiazepine receptor inverse agonist, FG7142. In subsequent experiments, an even larger increase in -adrenoceptor number was found 7 days after a single injection of this compound. The present experiments investigated whether FG7142-induced changes in adrenoceptor binding are also found in the rat and whether the effects of a single and repeated injections of this drug differ quantitatively. In view of the anxiogenic effects of FG7142, we have also tested for parallel changes in behaviours associated with anxiety and exploration. Nine days after a single injection of FG7142, the number of -adrenoceptors in the cerebral cortex was greater than that found after repeated administration of this compound; this difference was statistically significant. There was no difference in -adrenoceptor binding to tissues from chronically FG7142-treated and vehicle-injected animals and there were no changes in ₂-adrenoceptor binding or noradrenaline levels after either a single or repeated FG7142 treatment. Neither single nor repeated FG7142 treatment modified spontaneous behaviour in either the elevated plus-maze test of anxiety or the holeboard test of exploration. The behavioural effects of yohimbine and clenbuterol in these tests were also unaffected by FG7142. We discuss the possibility that the difference in the effects of a single and repeated administration of FG7142 on -adrenoceptor binding is related to the expression of kindled seizures.     

D-二聚体与纤维蛋白原检测评价慢性阻塞性肺疾病严重程度的价值研究

目的探讨D-二聚体(D-D)、纤维蛋白原(FG)检测评价慢性阻塞性肺疾病(COPD)严重程度的临床价值。方法选取我院2016年8月至2017年8月收治的63例慢性阻塞性肺疾病患者作为COPD组, 40例同期体检健康者作为健康组;将COPD组患者根据生存情况分为存活组、死亡组,并根据疾病严重程度进行分级;检测并比较各组的血浆D-D、 FG水平。结果 COPD组的D-D、 FG水平显著高于健康组(P <0.05)。死亡组患者的D-D、 FG水平显著高于存活组(P <0.05)。GOLD分级D级患者的D-D、 FG水平显著高于B级、 C级(P <0.05), B级、 C级患者的D-D、 FG水平无统计学差异(P>0.05)。结论 D-二聚体、纤维蛋白原水平越高, COPD的病情越严重,预后也越差,两者可作为评估COPD严重程度的临床指标。     

FG 7142 selectively decreases nonpunished responding,but has no anxiogenic effects on time allocation in a conflict schedule

Previous work (Thomas et al. 1990) showed that an anxiolytic benzodiazepine increased the time allocated to responding in a conflict situation (where responses were both food-reinforced and shock-punished) versus a nonpunishment situation. The present experiment tested whether a benzodiazepine-receptor inverse agonist (FG 7142, 1–30 mg/kg) would have the opposite effect (i.e., decrease time spent responding in a punishment situation). Chain pulls determined whether a rat's lever presses were reinforced on 1) a lean variable-interval schedule, or 2) a richer variable-interval schedule in which responding also produced shock intermittently. FG 7142 dose-dependently decreased nonpunished lever responding, but did not affect punished responding. The drug nonselectively decreased chain pulling (the schedule-switching response). Like chlordiazepoxide, FG 7142 increased the time spent in the punishment component, showing that not all effects of benzodiazepine-receptor agonists and inverse agonists are opposite. These results are inconsistent with expectations that anxiogenic actions of FG 7142 should 1) decrease punished responding; 2) increase the rate of responses that terminate the punishment condition; and 3) decrease time spent in the punishment component. Rather, nonsuppressed responding seems most sensitive to decreases by FG 7142.     

Conditioned place aversion produced by FG 7142 is attenuated by haloperidol

A place conditioning paradigm was used to examine the affective properties of FG 7142, a benzodiazepine receptor inverse agonist. At the highest dose tested (10 mg/kg, IP), FG 7142 produced a significant place aversion to the drug-paired compartment. In a second experiment, haloperidol injections were given before FG 7142. It was found that haloperidol (0.2 mg/kg) significantly reduced the measured conditioned place aversion produced by FG 7142, without exhibiting any aversive or rewarding effects by itself. These results suggest that dopamine receptors are involved in the learning or expression of conditioned place aversion induced by benzodiazepine receptor inverse agonists.     

FG020326-loaded nanoparticle with PEG and PDLLA improved pharmacodynamics of reversing multidrug resistance in vitro and in vivo

Aim： FG020326, a novel imidazole derivative, is a potent multidrug-resistance （MDR） modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-1oaded nanoparticle formed with diblock copolymers of poly （ethylene glycol）-block-poly （D,L-lactic acid） （PEG：PDLLA, PEDLLA） that can solubilize FG020326. This work was intended to evaluate the pharmacodynamics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo. Methods： Cytotoxicity was determined by tetrazolium assay. The intracellular accumulation and efflux of doxorubicin （Dox） were detected by fluorescence spectrophotometry. The function of P-glycoprotein was examined by Rhodamine 123 （Rh123） accumu- lation detected by flow cytometry. The KBv200 cell xenograft model was established to investigate the effect of PEDLLA-FG020326 on reversing MDR in vivo. Resdts： PEDLLA-FG020326 and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to vincristine （VCR） resistance, respectively and 14.98- and 7.64-fold to Dox resistance, respectively. PEDLLA-FG020326 was much stronger than FG020326, resulting in the increase of Dox and Rh123 accumulation and the decrease of intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA- FG020326 exhibited more powerful activity than FG020326 in enhancing the effect of VCR against KBv200 cell xenografts in nude mice, but did not appear more toxic. Conclusion： The pharmacodynamics of FG020326 was improved by incorporating it into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.     

大鼠阴茎包皮和包皮系带内nNOS免疫阳性神经末梢的分布与起源

目的观察成年SD大鼠阴茎包皮和包皮系带内神经型一氧化氮合酶(nNOS)免疫阳性神经末梢的分布和起源。方法免疫组织化学法观察nNOS免疫阳性神经末梢的分布,荧光金(Fluoro-gold,FG)逆行追踪和nNOS免疫荧光标记相结合法研究大鼠包皮系带内nNOS免疫阳性神经末梢的起源。结果成年SD大鼠阴茎包皮和包皮系带内均有nNOS免疫阳性神经末梢存在,这些神经末梢主要位于表皮基底层和真皮乳头层,呈树枝状或念珠状分布。阴茎系带处nNOS免疫阳性神经末梢的图像光密度值(3.4±0.38)明显大于阴茎包皮处(2.2±0.45)。FG逆标阳性细胞位于大鼠第六腰髓对应的背根神经节(L6-DRG)(9.6±1.2)个/mm2和第一骶髓对应的背根神经节(S1-DRG)(1.2±0.2个/mm2)内。阳性细胞大中小不等,大多沿神经束成行排列或散在分布。nNOS免疫荧光标记细胞在L6-DRG和S1-DRG内分别为(24.2±2.6)个/mm2和(24.1±2.1)个/mm2,细胞大多呈中小型。FG/nNOS双标阳性细胞均为中小型,其数量接近FG逆标阳性细胞总数的一半。结论大鼠阴茎包皮系带内含有浓密的nNOS免疫阳性神经末梢,这些神经末梢源自于L6-DRG和S1-DRG。     

Buckling Behavior of Sandwich Cylindrical Shells Covered by Functionally Graded Coatings with Clamped Boundary Conditions under Hydrostatic Pressure

The buckling behavior of sandwich shells with functionally graded (FG) coatings operating under different external pressures was generally investigated under simply supported boundary conditions. Since it is very difficult to determine the approximation functions satisfying clamped boundary conditions and to solve the basic equations analytically within the framework of first order shear deformation theory (FOST), the number of publications on this subject is very limited. An analytical solution to the buckling problem of FG-coated cylindrical shells under clamped boundary conditions subjected to uniform hydrostatic pressure within the FOST framework is presented for the first time. By mathematical modeling of the FG coatings, the constitutive relations and basic equations of sandwich cylindrical shells within the FOST framework are obtained. Analytical solutions of the basic equations in the framework of the Donnell shell theory, obtained using the Galerkin method, is carried out using new approximation functions that satisfy clamped boundary conditions. Finally, the influences of FG models and volume fractions on the hydrostatic buckling pressure within the FOST and classical shell theory (CT) frameworks are investigated in detail.     

Immunocytochemical evidence that most sensory neurons of the rat molar pulp express receptors for both glial cell line-derived neurotrophic factor and nerve growth factor

Most pulpal afferent neurons have cytochemical features in common with the class of nociceptors that express neuropeptides and respond to NGF, while very few bind the plant lectin IB4, a widely used marker for the class of nociceptors that respond to the GDNF family of neurotrophic factors. The present study was undertaken to determine whether the GDNF receptor, GFRalpha-1, is expressed by pulpal afferents, and, further, to determine whether tooth injury evokes changes in expression of the GDNF and NGF receptors among pulpal afferents. The tracer, fluoro-gold (FG), was applied to shallow cavities in dentin of first and second maxillary molars. After 4 weeks, the molars of one side received a test injury consisting of a deeper cavity that exposed pulp horns. Animals were perfusion fixed 2 days later, and sections of the trigeminal ganglia were double immunostained with combinations of antibodies against GFRalpha-1, and TrkA. Under control conditions, GFRalpha-1 immunostaining was observed in 72% of neurons that projected to the molar pulp, TrkA in 78%, and immunostaining for both receptors was observed in 65% of pulpal afferents. Tooth injury evoked up-regulation of GFRalpha-1 expression (to 93%) and a slight down-regulation of TrkA expression (67%) among tooth afferents, while there was no discernable change in the proportion of pulpal afferents that expressed both TrkA and GFRalpha-1 (to 61%).