侧脑室注射生长抑素对大鼠痛阈和电针镇痛作用的影响

观察脑内生长抑素对痛阈和针刺镇痛的影响。以钾离子透入引起大鼠甩尾为测痛方法,侧脑室注射生长抑素,生长抑素的耗竭剂半胱胺和抗生长抑素血清,电针刺激大鼠足三里。侧脑室注射ＳＳ使大鼠痛阈升高并使电针镇痛的效应增强,侧脑室分别注射ＣＳＨ和ＡＳＳＳ使大鼠前阈降低并使电针镇痛的效应减弱。     

益气活血平肝汤治疗高血压肾病患者临床疗效及血同型半胱胺酸影响

目的：观察中药益气活血平肝汤结合常规西药对高血压肾病（HN）患者的临床疗效及血同型半胱胺酸（tHcy）的影响。方法：选择HN患者100例进行前瞻性随机对照临床试验。治疗组和对照组各50例,治疗组给予西药常规治疗基础上加益气活血平肝汤加减治疗,对照组用西药常规治疗,疗程均为2个月。观察患者I瞄床疗效,并检测治疗前和治疗2个月后血同型半胱胺酸含量、24h尿蛋白定量、血肌酐、尿素氮水平。结果：总有效率治疗组76％,对照组52％,两组比较,差异有显著性意义（P〈0．05）;治疗两组血同型半胱胺酸（tHcy）含量分别与治疗前比较,差异均有显著性意义（P〈0．05）,两组治疗后24h尿蛋白定量、血肌酐、尿素氮比较,差异均有显著性意义（P〈0．05）。结论：益气活血平肝汤结合常规西药能有效改善HN的临床症状,降低血同型半胱胺酸含量,降低24h尿蛋白定量、血肌酐、尿素氮水平。     

Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors

1. Neurogenic plasma extravasation evoked by topical application of 1% vv⁻¹ mustard oil on the skin of the acutely denervated rat hindleg (primary reaction) inhibited the development of a subsequent oil-induced plasma extravasation induced in the skin of the contralateral hindleg by 49.3±7.06% (n=9) and in the conjunctival mucosa due to 0.1% wv⁻¹ capsaicin instillation by 33.5±10.05% (n=6). The primary reaction also inhibited the non-neurogenic hindpaw oedema evoked by s.c. injection of 5% wv⁻¹ dextran into the chronically denervated hindpaw by 48.0±4.6% (n=5).
2. Capsaicin injection (100 μg ml⁻¹ in 50 μl, s.c.) into the acutely denervated hindleg caused 56.5±4.0% (n=5) inhibition in the intensity of plasma extravasation elicited by 1% vv⁻¹ mustard oil smearing on the contralateral side. After chronic denervation, subplantar injection of 5% wv⁻¹ dextran elicited a non-neurogenic inflammatory response with intensive tissue oedema without causing any systemic anti-inflammatory effect. Bilateral adrenalectomy did not inhibit the mustard oil-induced anti-inflammatory effect in the contralateral hindleg.
3. Pretreating the rats with polyclonal somatostatin antiserum (0.5 ml rat⁻¹, i.v.) or with the somatostatin depleting agent cysteamine (280 mg kg⁻¹, s.c.) prevented the inhibitory action of mustard oil-induced inflammation on subsequent neurogenic plasma extravasation and strongly diminished the inhibition of non-neurogenic oedema formation evoked by dextran.
4. Exogenous somatostatin (10 μg kg⁻¹, i.p.) caused a 30.3±8.3% (n=6) inhibition of plasma extravasation caused by mustard oil smearing on the acutely denervated hindleg and this inhibitory effect was abolished by somatostatin antiserum (0.5 ml rat⁻¹, i.v.). The plasma level of somatostatin-like immunoreactivity (SST-LI) increased by 40.03±6.8% (n=6) 10 min after topical application of 1% vv⁻¹ mustard oil on the acutely denervated hindpaws compared to the paraffin oil treated control group. Chronic denervation of the hindlegs or cysteamine (280 mg kg⁻¹, s.c.) pretreatment prevented the mustard oil-induced elevation of SST-LI in plasma.
5. It is concluded that chemical excitation of the capsaicin-sensitive sensory receptors not only induces local neurogenic plasma extravasation but also inhibits the development of a subsequent inflammatory reaction at remote sites of the body in the rat. A role for somatostatin in this systemic anti-inflammatory effect is suggested.

     

哮喘儿童外周血Cys LTs、MCP-4及MDC检测及临床意义

目的 分析哮喘患儿外周血半胱胺酰白三烯(Cys LTs)、单核细胞趋化蛋白-4(MCP-4)、巨噬细胞衍生趋化因子(MDC)表达及其临床应用价值。方法 以2016年6月-2018年6月在青岛大学附属市立医院就诊的220例儿童为研究对象,48例哮喘急性期儿童为哮喘急性发作组,52例哮喘缓解期儿童为哮喘缓解期,64例肺炎儿童为肺炎组,56例健康儿童为对照组,比较各组Cys LTs、MCP-4及MDC血清水平。结果 Cys LTs、MCP-4、MDC血清水平哮喘急性发作组均高于缓解期、肺炎组及正常对照组(P<0.05);肺炎组与哮喘缓解期间差异无统计学意义(P>0.05),但均高于正常对照组,差异均有统计学意义(P＜0.05);不同严重程度哮喘儿童外周血Cys LTs、MCP-4、MDC水平间歇组、轻度组及中重度组依次升高,两两比较差异均有统计学意义(P＜0.05);Cys LTs、MDC与MCP-4;Cys LTs 与 MDC均呈正相关(r=0.865、0.812、0.893,P＜0.01)。结论 Cys LTs、MCP-4及MDC参与了哮喘的多个环节,外周血Cys LTs、MCP-4及MDC对儿童哮喘病情评估有重要的临床应用价值。     

Effect of cysteamine on insulin release and exocrine pancreatic secretionin vitro

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380±70 vs 100±20 fmol/20 min), inhibited insulin output (890±120 vs 13210±3260 units/20 min) and reduced exocrine pancreatic secretion (volume: 12±2 vs 20±2 l/20 min; lipase: 31±3 vs 60±7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.This study was supported by the Deutsche Forschugsgemeinschaft (DFG grant Mu 543/3-3).     

Synthesis and pharmacological evaluation of novel derivatives of anti‐inflammatory drugs with increased antioxidant and anti‐inflammatory activities

The role of reactive oxygen species in inflammatory processes has been well documented, while several antioxidant compounds have been shown to exhibit anti‐inflammatory activity. We designed novel compounds as potential agents that combine enhanced antioxidant and anti‐inflammatory activities. Derivatives of indomethacin, diclofenac, tolfenamic acid, and ibuprofen, four widely used nonsteroidal anti‐inflammatory drugs, with cysteamine, a polar antioxidant molecule, were synthesized. The compounds were evaluated for their effect on free radical processes (protection against rat hepatic microsomal lipid‐peroxidation and interaction with the stable free radical 1,1‐diphenyl‐2‐picrylhydrazyl), as well as on carrageenan‐induced inflammation (mouse paw edema inhibition). Furthermore, ulcerogenicity tests in rats were performed in order to evaluate the gastrointestinal irritation of the novel indomentacin derivative. It was found that all compounds were very potent antioxidants in vitro; they could inhibit lipid peroxidation very significantly, having IC₅₀ values ranging from 55 to 510 μM, while they could also interact ∼90% with DPPH at equimolar concentrations. We attribute these activities to their sulfhydryl group, as well as to their increased lipophilicity compared to cysteamine. Furthermore, the derivatives demonstrated significant anti‐inflammatory activity, comparable to that of the parent molecules, while they showed significantly reduced ulcerogenic potency. Our results indicate that the combined pharmacological properties of these new derivatives may prove useful for the design and development of novel cytoprotective/anti‐inflammatory molecules with potentially important therapeutic applications. Drug Dev. Res. 47:9–16, 1999. © 1999 Wiley‐Liss, Inc.     

EFFECT OF DIMETHYLSULPHOXIDE ON CYSTEAMINE-INDUCED DUODENAL ULCERATION IN RATS

1. Rats were pretreated with dimethylsulphoxide (DMSO) at concentrations of 2, 4 and 6% v/v in the drinking water for 7 days, then injected with a single subcutaneous dose of cysteamine (28 mg/100 g bodyweight) to induce duodenal ulceration. 2. DMSO reduced, in a dose-dependent manner, the incidence and extent of the ulceration. 3. Mucus duodenal content was not significantly affected by either DMSO or cysteamine treatments.