不同首剂量的牛肺表面活性剂对新生儿呼吸窘迫综合征的疗效

目的 通过分析肺表面活性物质（PS）的不同首剂量对新生儿呼吸窘迫综合征（NRDS）的临床疗效。方法 选取2015年4月—2018年3月在平顶山市第一人民医院收治确诊的NRDS 100例作为研究对象,采用随机数字表法分为70 mg/kg剂量组和100 mg/kg剂量组,每组各50例,分别给予注射用牛肺表面活性剂首剂量70、100 mg/kg出生体质量的治疗剂量。比较两组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率及治疗前后的氧分压（pO₂）、二氧化碳分压（pCO₂）、吸入氧浓度（FiO₂）、平均动脉压（MAP）。结果 治疗后,100 mg/kg组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率均低于70 mg/kg组,差异均有统计学意义（P<0.05）,但两组患儿住院时间相比没有显著差异。两组患儿经过治疗后pO₂、pCO₂、FiO₂、MAP均优于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）,其中100 mg/kg组患儿治疗后pCO₂、FiO₂、MAP明显优于70 mg/kg组,差异有统计学意义（P<0.05）,但治疗后两组pO₂差异无统计学意义。结论 注射用牛肺表面活性剂首剂量100 mg/kg出生体质量应用于新生儿呼吸窘迫综合症,能有效显著缩短患儿的氧疗时间及住院时间,降低住院肺炎发生率,具有较好的临床应用价值。     

珠贝定喘丸联合沙美特罗替卡松治疗儿童支气管哮喘的疗效观察

目的 探讨珠贝定喘丸联合沙美特罗替卡松治疗儿童支气管哮喘的临床效果。方法 选取2016年9月-2018年9月河南科技大学第一附属医院（开元院区）收治的支气管哮喘患儿116例,随机分为对照组（58例）和治疗组（58例）。对照组吸入沙美特罗替卡松气雾剂,1揿/次,1次/d;治疗组患儿在对照组的基础上口服珠贝定喘丸,3~4岁儿童1丸/次,5~6岁2丸/次,7~8岁3丸/次,9~10岁4丸/次,11~13岁5丸/次,3次/d。两组患儿连续治疗3个月。观察两组患者临床疗效,同时比较治疗前后两组患者症状和体征消失时间,肺功能指标一秒用力呼气容积（FEV₁）、用力肺活量（FVC）和FEV₁/FVC,及血气指标血氧分压（pO₂）和二氧化碳分压（pCO₂）。结果 治疗后,对照组和治疗组临床有效率分别为84.48%和96.55%,两组比较差异具有统计学意义（P<0.05）。治疗组患儿症状、体征消失时间均明显短于对照组（P<0.05）。治疗后,两组FEV₁、FVC、FEV₁/FVC均显著升高（P<0.05）,且治疗组明显高于对照组（P<0.05）。治疗后,两组患儿pO₂明显升高（P<0.05）,而pCO₂明显降低（P<0.05）;且治疗组患儿pO₂和pCO₂明显好于对照组（P<0.05）。结论 珠贝定喘丸联合沙美特罗替卡松治疗小儿支气管哮喘可显著提升疗效,有助于改善肺功能并缩短病程时间,且安全性较高。     

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As₂O₃ toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As₂O₃. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD₅₀ of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As₂O₃ poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As₂O₃ (containing a tracer dose of⁷⁴As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated.     

Studies on electroencephalogram (EEG) in rats suggest that moderate doses of cocaine ord-amphetamine activate D1 rather than D2 receptors

The effects of cocaine andd-amphetamine, two psychomotor stimulant drugs with pronounced addictive properties, on the electroencephalogram (EEG) of rats were studied by telemetric recordings from the skull in non-anesthetized, freely moving rats. The electrocorticogram (ECoG) was recorded. Both cocaine (10 mg/kg IP) andd-amphetamine (0.4 mg/kg IP) produced a desynchronization, characterized by a general lowering in power in all of the frequency bands. These effects of both drugs were mimicked by the selective agonist at D₁ receptors SK&F 38393 (3 mg/kg SC) and were reversed by the antagonist at D₁ receptors SCH 23390 (0.2 mg/kg IP) but not influenced by haloperidol (0.1 mg/kg IP) in a dose which is likely to block D₂ rather than D₁ receptors. These doses of cocaine ord-amphetamine did not produce stereotyped behaviour and slight, if any, increases in locomotor activity only. Large doses of cocaine (30 mg/kg IP) ord-amphetamine (4 mg/kg IP) produced stereotyped behaviour and alterations in EEG which are, based on previous own studies, characteristic for additional stimulation of D₂ receptors. This was manifest in a selective increase in power of the alpha-1 band. A similar effect was also produced by the agonist both at D₁ and D₂ receptors, apomorphine (0.5 mg/kg SC). These results suggest that moderate, but probably rewarding doses of cocaine ord-amphetamine mainly activate D₁ dopamine receptors. This activation might be relevant for the rewarding properties of these drugs.     

Cardiovascular effects of the adenosine A<Subscript>1</Subscript> receptor agonist<Emphasis Type="Italic"> N</Emphasis><Superscript>6</Superscript>-cyclopentyladenosine (CPA) decisive for its therapeutic efficacy in sarin poisoning

Mortality and occurrence of cholinergic symptoms upon sarin intoxication (144 µg/kg s.c., ~2×LD₅₀) in rats is completely prevented by treatment with the adenosine A₁ receptor agonist N⁶-cyclopentyladenosine (CPA, 2 mg/kg i.m.). Previously, we have shown that CPA treatment altered the distribution of sarin into the brain, presumably through its cardiovascular side effects. Therefore, the objective of the present study was to evaluate the contribution of the cardiodepressant effects of CPA to its therapeutic efficacy against sarin intoxication. Intramuscular treatment of rats with 0.5 and 2.0 mg/kg CPA 1 min after sarin poisoning attenuated most cholinergic symptoms and prevented mortality, which seemed to be directly associated with an immediate strong and long-lasting bradycardia and hypotension caused by CPA. Treatment with lower doses of CPA (0.1 and 0.05 mg/kg i.m.) caused similar levels of bradycardia and hypotension, albeit a few minutes later than at the higher doses of CPA. Upon sarin intoxication, this was correlated with increased incidence of cholinergic symptoms and decreased survival rates. Pretreatment with the peripheral adenosine A₁ receptor antagonist 8-p-sulphophenyltheophylline (8-PST, 20 mg/kg i.p.) counteracted the cardiodepressant effects of 0.05 mg/kg CPA almost completely, thereby nearly abolishing its therapeutic efficacy against sarin poisoning. In conclusion, the present results strongly indicate that bradycardia and hypotension induced by the peripheral adenosine A₁ receptor play a prominent role in the therapeutic efficacy of CPA in cases of sarin poisoning.     

Evidence that 5-HT2C receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety

Four non-selective 5-HT_2C/5-HT_2A receptor antagonists, mianserin (2–8 mg/kg), 1-naphthyl piperazine (1-NP) (0.5–1 mg/kg), ICI 169,369 (20 mg/kg) and LY 53857 (5 mg/kg), increased punished responding for a food reward in the rat Geller-Seifter test 30 min after subcutaneous (SC) administration. This property was shared by the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg SC). However, the selective 5-HT_2A receptor antagonists ketanserin (0.2–1 mg/kg SC) and altanserin (0.5, 1 mg/kg SC) had little effect. The 5-HT_1A, 5-HT_1B and-adrenergic receptor antagonists pindolol and cyanopindolol (6 mg/kg SC) did not affect punished responding either, nor did the 5-HT_1D receptor partial agonist and ₂ adrenergic receptor antagonist yohimbine (2.5 mg/kg SC) or the histamine H₁ receptor antagonist mepyramine (1 mg/kg SC). Unpunished responding was also modestly increased after some doses of the 5-HT_2C/5-HT_2A receptor antagonists. However, this effect was inconsistent and was also seen after chlordiazepoxide. Furthermore, it was not associated with the increase in punished responding observed in rats orally treated with mianserin (10, 20 mg/kg), 1-NP (10, 20 mg/kg) or ICI 169,369 (50 mg/kg). The action of the 5-HT_2C/5-HT_2A receptor antagonists tested is therefore consistent with anxiolysis. The results also strongly suggest that this effect is mediated by blockade of the 5-HT_2C receptor, although the possibility of 5-HT_2B receptor mediation is discussed.     

丁基苯酞对大脑中动脉阻断后皮层组织中花生四烯酸释放及磷脂酶A2基因表达的影响

目的　研究丁基苯酞（dl-NBP), d-NBP和 l-NBP对大脑中动脉阻断(MCAO) 6 h后缺血区皮层中花生四烯酸(AA)释放及磷脂酶A₂（PLA₂）基因表达的影响。方法　阻断大脑中动脉起始部造成局灶性脑缺血模型。HPLC检测AA。Northern blot检测皮层中PLA₂基因表达。结果　MCAO后6 h,皮层中AA释放明显增加。于脑缺血后5 min 和120 min,给dl-NBP(10或20 mg.kg^-1) 和尼莫地平(0.5 mg.kg^-1) 可显著抑制AA的释放。d-NBP和l-NBP作用比较,显示d-NBP有与dl-NBP相似的作用,而l-NBP则无明显影响。Northern印迹结果表明,脑缺血6 h,皮层中PLA₂的基因表达增强。 dl-NBP和d-NBP(10, 20 mg.kg^-1,ip)皆可使表达降低,而l-NBP对缺血脑组织中PLA₂的基因表达的升高无明显影响。结论　dl-NBP和d-NBP可抑制MCAO后脑组织中AA释放和PLA₂的基因表达。     

Some unusual effects of α2-adrenergic drugs on cortical high voltage spindles in rats

The dose-response curves for a number of α-adrenergic drugs were investigated to estimate a possible role of the α₂/α₁ selectivity of these drugs on the incidence of cortical high voltage spindles (HVS), reflecting level of vigilance. The α₂ antagonists yohimbine (0.25–4 mg/kg) and idazoxan (0.5–4 mg/kg), but not atipamezole induced a biphasic effect on the incidence of HVS in rats. This effect of relatively small doses of yohimbine and idazoxan should be taken into consideration when using these drugs as ga₂ antagonists in behavioral and neurophysiological tests. On the other hand the linearity of the dose-response curve for atipamezole (0.01–4 mg/kg) indicates that this drug is a good candidate for use in such tests.     

Endothelium-derived nitric oxide partially mediates salbutamol-induced vasodilatations

This study examined the ability of salbutamol (selective β₂-adrenoceptor agonist) to cause endothelium-dependent relaxation in rat aortic rings and depressor response in conscious rats. Salbutamol (0.01–100 μM) concentration dependently relaxed preconstricted aortic rings. The relaxant response was partially attenuated by either mechanical removal of the endothelium or treatment with N^G-nitro-l-arginine methyl ester (L-NAME, 100 μM). In conscious rats, either i.v. infused phenylephrine (5 μg/kg per min) or i.v. bolus injected L-NAME (12.8 mg/kg), but not the vehicle, caused similar sustained increases in mean arterial pressure (MAP). I.v. infused salbutamol (2–128 μg/kg per min, each dose for 5 min) dose dependently decreased MAP in vehicle-treated rats; the depressor responses were potentiated by hypertension induced by phenylephrine. In contrast, the magnitudes of the depressor response to salbutamol in L-NAME-treated rats were less than those in rats pretreated with phenylephrine or the vehicle. I.v. bolus injections of salbutamol (0.25–16 μg/kg) also caused dose-dependent and transient decreases in MAP in vehicle-treated rats. The magnitude but not the duration of the depressor response to salbutamol was less in rats treated with L-NAME, compared to those in rats given phenylephrine or the vehicle. These results suggest that endothelium-derived nitric oxide is partially involved in β₂-adrenoceptor-mediated vasodilatation.     

Hyperthermia induced bym-trifluoromethylphenylpiperazine (TFMPP) orm-chlorophenylpiperazine (m-CPP) in heat-adapted rats

TFMPP andm-CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) orm-CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT_1c and 5-HT₂ receptor antagonists mesulergine (0.5–4 mg/kg), ketanserin (0.6–2.5 mg/kg) and ritanserin (0.5–2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5–1 mg/kg), or was attenuated by the 5-HT_1A, 5-HT₂ and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT_1A, 5-HT_1B and adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT_1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- orm-CPP-induced hyperthermia. The 5-HT_1A and ₁-adrenoceptor antagonist NAN-190 (1–4 mg/kg), the 5-HT₃ antagonists tropisetron (0.01–1 mg/kg) and zacopride (0.5 and 1 mg/kg), the-blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP orm-CPP. The hyperthermias studied were not modified, in animals with 5-HT lesion produced byp-chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats. The obtained results suggest that the hyperthermia induced by TFMPP orm-CPP is mediated by 5-HT₂, and maybe also by 5-HT_1c receptors — those which are located postsynaptically.     

The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility

Aim: To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans. Methods: Eight healthy male volunteers, mean age 22 (19–28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T₀–T₂₄₀ min). Results: The LOS basal pressure (23.3 ± 2.0 cmH₂O; mean ± s.d.) remained stable after dosing with placebo to T₂₄₀ After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P= 0.036; 0.3 mg/kg, P= 0.027; 0.5 mg/kg, P= 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T₃₀ after lintopride 0.3 mg/kg (34.5 cmH₂O, P= 0.020) and 0.5 mg/kg (32.5 cmH₂O, P=-0.027), at T₆₀ after 0.3 mg/kg (48.8 cmH₂O, P= 0.0009) and 0.5 mg kg (29.1 cmH₂O, P= 0.029) and at T₆₀ after 0.3 mg/kg (34.5 cmH₂O, P= 0.0018). Conclusions: Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.     

Lithium decreases 5-HT1A and 5-HT2 receptor and α2-adrenoreceptor mediated function in mice

Lithium administration (LiCl, 10 mmol/kg, SC on day 1, followed by 3 mmol/kg twice daily subsequently) for 14 days to mice produced attenuation of the hypothermic response to injection of 8-hydroxy-2-(di-n-propyla-mino)tetralin (8-OH-DPAT, 0.5 mg/kg SC). Head twitch responses to the 5-HT-receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg IP) and to precursor loading with carbidopa (25 mg/kg, IP) and 5-hydroxytryptophan (100 mg/kg IP) were similarly attenuated. By contrast with this reduction of 5-hydroxytryptamine (5-HT) function mediated by the 5-HT_1A and 5-HT₂ receptor sub-types, repeated lithium administration had no effect on the motor response to a putative 5-HT_1B receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969, 3 mg/kg IP). Alpha₂ adrenoceptor function, assessed by the sedation response to clonidine (0.25 mg/kg, IP), was also attenuated by repeated lithium administration. It is proposed that these actions may explain the emergence of lithium as an adjunct to the treatment of refractory depressive illness.     

Phase I and pharmacokinetic study of etaracizumab (Abegrin™), a humanized monoclonal antibody against α<Subscript>v</Subscript>β<Subscript>3</Subscript> integrin receptor,in patients with advanced solid tumors

Summary This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the α_vβ₃ integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials.     

芪苈强心胶囊联合坎地沙坦酯治疗慢性肺心病急性加重期的疗效观察

目的探索芪苈强心胶囊联合坎地沙坦酯治疗慢性肺心病急性加重期的治疗疗效。方法选取2016年1月—2016年12月于北京市隆福医院接受治疗的慢性肺心病急性加重期患者86例,随机分成对照组和治疗组,每组各43例。对照组口服坎地沙坦酯片,4 mg/次,1次/d。治疗组在对照组治疗基础上口服芪苈强心胶囊,4粒/次,3次/d。两组患者均连续治疗2周。观察两组的临床疗效,同时比较两组治疗前后氧分压、二氧化碳分压、血氧饱和度的变化情况。随访120 d,评价两组患者的生活质量评分。结果治疗后,对照组和治疗组的总有效率分别为79.07%、90.70%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者氧分压、血氧饱和度均显著升高,同组治疗前后差异有统计学意义(P0.05);治疗后,治疗组氧分压、血氧饱和度均显著高于对照组,两组比较差异具有统计学意义(P0.05)。随访后,两组生活质量评分均显著升高,同组治疗前后差异有统计学意义(P0.05);随访后,治疗组生活质量评分高于对照组,两组比较差异具有统计学意义(P0.05)。结论芪苈强心胶囊联合坎地沙坦酯治疗慢性肺心病急性加重期有显著效果,可显著改善血气分析指标和生活质量评分,具有一定的临床推广应用价值。     

Aβ2受体激动剂息喘酚的中枢抑制作用

息喘酚(hexoprenaline)化学名为N,N’-双[2-(3’,4’-二羟苯基)-2-羟乙基]-已二胺盐酸盐。1963年由奥地利Linz药厂合成,七十年代进行了广泛的药理研究,证明属Aβ_2受体激动剂,有良好的平喘作用,已被应用于临床。但对息喘酚的中枢作用迄今未见报告。     

Metabolism and pharmacokinetics in rats of ganoderiol F,a highly cytotoxic and antitumor triterpene from <Emphasis Type="Italic">Ganoderma lucidum</Emphasis>

The metabolism of ganoderiol F (GF), a cytotoxic and antitumor triterpene from Ganoderma lucidum, by intestinal bacteria and its pharmacokinetics in rats were investigated by using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). GF was converted to ganodermatriol by anaerobic incubation with bacterial mixtures from rats and humans. This metabolite was detected in rat feces, but not in plasma and urine, after oral administration of GF. The fate of GF after oral (p.o.) and intravenous (i.v.) administration to rats was examined in pharmacokinetics studies. Plasma samples pretreated by solid-phase extraction were quantified by HPLC/MS/MS over a GF concentration range of 1.25–100 ng/ml (S/N = 5). The intra- and interday precision (CV%) was below 8% and accuracy was within the range of 95.9–103.6% for all samples. The range of recovery ratios was 89.2–98.2%. After the administration of GF at 0.5 mg/kg i.v., the plasma concentrations of GF quickly declined and the elimination half-life values (t _1/2α and t _1/2β) were about 2.4 and 34.8 min. On the other hand, the elimination half-life values (t _1/2α) after p.o. administration of GF at doses of 20 and 50 mg/kg were 14.4 and 143.3 min for the former, and 18.6 and 114.6 min for the latter. The AUC_0–t value was 11.17 (ng/ml) h at a GF dose of 0.5 mg/kg i.v., but 49.4 and 111.6 (ng/ml) h at GF doses of 20 and 50 mg/kg p.o., respectively, indicating that the AUC_0–t value is proportional to the administered oral doses. The estimated absolute bioavailability of GF in rats was F = 0.105.     

山莨菪碱对乙酰胆碱和去甲肾上腺素引起的兔虹膜释放前列腺素的影响

本文研究了654-2对Ach及NE引起的兔虹膜释放PGE₂及6-keto-PGF_1α作用的影响。Ach及NE使虹膜释放PGs增加,654-2对Ach释放PGs的作用呈剂量依赖性抑制,当654-2浓度为3×10^-5mol/L时,Ach(5x10^-5mol/L)引起的PGE₂及6-keto-PGF_1α的释放量分别降低31%及30%。654-2浓度高于6x10^-5mol/L时显著抑制NE(5x10^-5mol/L)释放虹膜PGs的作用,当654-2浓度为3x10^-4mol/L时,使NE增加虹膜释放PGE:及6-keto-PGF_1α的量分别从62%及34%降至7.5%及4%(p<0.01)。654-2抑制PGs释放对其抗感染性休克等作用可能是有利的。     

Evidence for 5-HT2 receptor mediation in quipazine anorexia

Doses ofd-amphetamine (3.2 mg/kg), fenfluramine (10 mg/kg) and quipazine (8 mg/kg) cause a significant reduction in food intake during a 30-min daily feeding session in food-deprived rats. Pirenperone and ritanserin, 5-HT₂ receptor antagonists, significantly blocked the anorectic effect of quipazine, whiled-amphetamine and fenfluramine effects were not modified. Metergoline, a non-specific blocker of 5-HT receptors, significantly blocked the anorectic effects of fenfluramine and quipazine, but not thed-amphetamine effect. Pretreatment with alpha- and beta-adrenergic receptor antagonists (prazosin, propranolol and pindolol), dopamine receptor antagonists (haloperidol and pimozide), the catecholamine synthesis inhibitor alphamethyl-para-tyrosine, and the opioid receptor antagonist naloxone failed to modify the anorectic effects of all three agents, with the exception that quipazine-induced anorexia was significantly reduced by pimozide. These results suggest that the quipazine anorexia is largely mediating through 5-HT₂ receptors, although the effect of pimozide remains to be explained. Consistent with previous studies, the fenfluramine effect appears to be mediated through 5-HT_1B receptors. Receptors involved in the anorectic effect of higher doses ofd-amphetamine are still unidentified by this analysis. Further investigation is required to define the mechanisms by which quipazine and larger doses ofd-amphetamine bring about a reduced appetite for food.     

Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats

Blocking glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptor complex with MK-801 (0.15–0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed afterd-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D₂ dopamine receptor antagonist raclopride (0.1–0.3 mg/kg, SC) and by the D₁ receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reducedd-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects ofd-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced byd-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.     

百令胶囊联合比阿培南治疗肺气肿的临床研究

目的探讨百令胶囊联合比阿培南治疗肺气肿的临床效果。方法收集2013年1月—2015年12月在河北大学附属医院接受治疗的104例肺气肿患者,随机分为对照组和治疗组,每组各52例。对照组患者静脉滴注注射用比阿培南,0.6 g溶于100 m L生理盐水,2次/d。治疗组在对照组的基础上口服百令胶囊,5~10粒/次,3次/d。两组患者持续治疗8周。治疗后评价两组患者临床疗效,同时比较分析两组患者治疗前后第1秒呼气量(FEV1)、用力肺活量(FVC)、肺活量(VC)、最大通气量(MVV)、动脉血气饱和度、二氧化碳分压(pCO_2)、氧分压(pO_2)、动脉氧分压、氧合指数、细菌清除率和血清C反应蛋白(CRP)改变。结果治疗后,对照组的有效率为78.85%,显著低于治疗组的88.46%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后,两组患者FEV1、FVC、VC和MVV水平均显著升高(P0.05),且治疗后治疗组患者上述肺功能指标升高的更显著(P0.05)。治疗后,两组氧合指数、pO_2、动脉氧分压、动脉血气饱和度明显升高,pCO_2明显下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组患者血气指标结果明显优于对照组,两组治疗后比较差异具有统计学意义(P0.05)。治疗后,治疗组细菌清除率明显高于对照组,且治疗组血清CRP含量明显比对照组低,两组细菌清除效果和CRP比较差异具有统计学意义(P0.05)。结论百令胶囊联合比阿培南能够明显提高肺气肿患者的治疗效果,对于改善肺气肿患者肺部功能、降低体内炎症水平具有重要作用。