Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles.

2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator durgs.     

COPD大鼠肺组织中 LTB4水平、5 LOmRNA表达及齐留通的干预作用

目的探讨慢性阻塞性肺疾病(chronicobstructivepulmonarydisease,COPD)大鼠模型肺组织中白三烯 B4(LeukotrieneB4, LTB4)含量与5 脂氧合酶(5 LO,5 lipoxygenase)mRNA水平的变化,以及给予齐留通干预的影响.方法36只健康雄性 Wistar大鼠随机分为对照组、模型组、药物组,采用被动吸烟法制作 COPD大鼠模型,给予药物组鼻饲齐留通,测定肺功能,各组肺组织匀浆检测其 LTB4含量及髓过氧化物酶(Myeloperoxidase,MPO)活性,RT PCR法检测5 LOmRAN的表达.结果模型组、药物组的0.3秒用力呼吸容积(Forcedexpiratoryvolumeinthe0.3second,FEV0.3)/用力肺活量(Forcedvitalcapacity,FVC)%较对照组显著下降(P<0.001),吸气相阻力(Inspiratoryphaseresistance,Ri)和呼气相阻力(expiratoryphaseresistance,Re)较对照组显著增加(P<0.001,P<0.05);模型组较药物组 FEV0.3/FVC%下降程度更低,Ri、Re更高,两组间差异有显著性(P<0.05).比较各组大鼠肺组织 LTB4水平,MPO活性及5 LOmRNA表达:模型组、药物组较对照组显著升高(P<0.001);与模型组比较,齐留通干预使得三项指标均有显著降低(P<0.001).结论 LTB4及5 LO参与 COPD的气道炎症过程.5 LOX抑制剂齐留通可部分抑制减少 COPD大鼠肺组织中 LTB4产生,其机制可能为抑制5 LO表达     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles

Summary 2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator drugs.Deceased, May 31, 1978.     

慢性酒精性胰腺炎中CD14、TLR4、TNFα的表达

目的 研究酒精性慢性胰腺炎组织中白细胞分化抗原14(CD14)、钟样受体4(TLR4)、肿瘤坏死因子(TNFα)的表达,探讨酒精性慢性胰腺炎的发病机制.方法 24只1月龄雄性SD大鼠随机分为对照组、脂多糖组、酒精组、酒精联合脂多糖组(以下简称联合组)各6只.酒精组和联合组饲以25％酒精,饮酒12用后联合组和脂多糖组,反复腹腔注射脂多糖2 mg/kg·w,共4次.用免疫组化及RT-PCR检测CD14、TLR4、TNF在各组的表达.结果 酒精组CD14、TLR4和TNF表达较对照组和脂多糖组增加(P＜0.05),联合组CD14、TLR4和TNF表达较对照组、脂多糖组明显增加(P＜0.01),较酒精组增加(P＜0.05).结论 酒精性慢性胰腺炎组织中CD14、TLR4和TNF表达增加,脂多糖通路可能参与了慢性胰腺炎发生发展.     

Developmental change of EEG in rat from 4th to 16th week

Summary The development of EEG in 8 male rats from 4 to 16 weeks age were studied chronically. Theta band had the highest power at 5–16 weeks. Especially after 11 weeks, theta band presented a signigicantly higher peak than that of 4-week-old. In contrast to this, delta band, which had the highest power at 4 weeks, was markedly decreased.     

Developmental change of EEG in rat from 4th to 16th week.

The development of EEG in 8 male rats from 4 to 16 weeks age were studied chronically. Theta band had the highest power at 5--16 weeks. Especially after 11 weeks, theta band presented a significantly higher peak than that of 4-week-old. In contrast to this, delta band, which had the highest power at 4 weeks, was markedly decreased.     

Protection by cerium chloride on CCl4-induced hepatotoxicity

Summary Pretreatment of rats with cerium chloride, an inhibitor of the DMES, protects against CCl₄ intoxication. The protection was obtained against the fatty infiltration in the liver, the decrease of triglyceride secretion from the liver into the plasma compartment, the polysomal disaggregation and the rise of serum transaminases.     

Protection by cerium chloride on CCl4-induced hepatotoxicity.

Pretreatment of rats with cerium chloride, an inhibitor of the DMES, protect against CCl4 intoxication. The protection was obtained against the fatty infiltration in the liver, the decrease of triglyceride secretion from the liver into the plasma compartment, the polysomal disaggregation and the rise of serum transaminases.     

Chemotherapeutic effects of 4-isothiocyanato-4'-nitrodiphenylamine (C9333-Go/CGP 4540) on infections with Nematospiroides dubius, Hymenolepis diminuta, Hymenolepis nana and Spirometra mansonoides.

4-Isothiocyanato-4'-nitrodiphenylamine possessed anthelmintic activity against Nippostrongylus dubius and Hymenolepis nana in mice and H. diminuta in rats as determined by both egg counts and recovery of parasites at autopsy. No activity was detected against the cestode. Spirometra mansonoides, in cats.     

Quantitative Versuche zur Krebserzeugung mit 4-Dimethylamino-stilben an Ratten

Summary Quantitative experiments in rats fed with 4-dimethylaminostilbene proved that the induction of ear-duct cancer is an irreversible summation action, similar to the production of hepatomas with 4-dimethylaminoazobenzene.

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Die Arbeiten wurden durch die Deutsche Forschungsgemeinschaft ermöglicht.     

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate.

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5 alpha-dihydrotestosterone (DHT).     

3-Hydroxy-4-methoxyphenethylamine,the cardioactive constituent of a soft coral

Summary Intravenous administration to rats of the aqueous extract of the soft coralNephthea sp. caused an increase in heart rate and blood pressure. The cardioactive constituent was isolated and shown to be 3-hydroxy-4-methoxyphenethylamine.     

盐酸戊乙奎醚对大鼠感染性脑水肿AQP4表达的影响

目的：研究盐酸戊乙奎醚对感染性脑水肿保护作用的机制。方法：采用左颈内动脉注射脂多糖复制大鼠感染性脑水肿模型,将84只雄性SD大鼠随机分为对照组（C组）、水肿组（I组）、盐酸戊乙奎醚治疗组（P组）。检测6h、12h、24h、48h时各组大鼠脑组织含水量、病理形态;脑组织SOD活性、MDA含量;免疫组化法及RT—PCR法检测AQP4蛋白分布与AQP4mRNA含量。结果：（1）与C组相比,I组、P组脑含水量、MDA含量均升高,同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少（P〈0．01）。与对应时间点P组相比,I组脑含水量、MDA含量均升高,同时SOD活性、AQP4蛋白、AQP4mRNA表达均减少,于24h达高峰,48h仍在较高水平（P〈0．01）。（2）脑组织光镜检查：I组大鼠脑组织损伤严重,P组损伤明显减轻。结论：盐酸戊乙奎醚能在一定程度上可减轻感染所致的脑组织损伤,上调AQP4表达,对脑水肿有一定治疗作用,其机制可能与抗氧化作用有关。     

Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis

Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents, which play key roles in inflammatory and allergic diseases. The committed step in cys-LT biosynthesis is catalyzed by leukotriene C₄ synthase (LTC4S) as well as microsomal glutathione S-transferase type 2 (MGST2) and type 3 (MGST3). Here we report that intraperitoneal injections of lipopolysaccharide in rats lead to a strong increase of LTC4S messenger RNA (mRNA) levels after approximately 1 h, particularly in the heart, brain, adrenal glands and liver, without any significant effect on MGST2 and MGST3 mRNA levels. After 6 h, LTC4S mRNA returns to basal levels, concomitant with a 4.9-, 4.0-, 2.9- and 2.3-fold induction of LTC4S protein in brain, heart, liver and adrenal gland, respectively. Hence, challenge with lipopolysaccharide in vivo causes an organ-selective, local priming for leukotriene C₄ synthesis. Moreover, these data suggest that LTC4S and cys-LTs may be involved in acute systemic inflammatory responses such as fever and tachycardia.Received 12 August 2004; received after revision 27 October 2004; accepted 1 November 2004     

Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4′-fluorobiphenyl) acetamide

Summary Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.     

4,5,6,7-Tetrahydro-7-oxobenzo[b]thien-4-ylurea; Sulbenox1, a novel animal growth stimulant

The title compound, a metabolite of 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, was synthesized and found to be an effective growth promoter in sheep, mice, and rats. In sheep it gave over a 6-week growth period at 15 and 60 ppm in the diet an economically and statistically significant growth response.     

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate

Summary Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5-dihydrotestosterone (DHT).Supported in part by the project fund (grant 53-403) of Kawasaki Medical School.The authors would like to thank the Central Laboratory, Sankyo Pharmaceutical Co., Tokyo, for supplying 19-nortestosterone-17-ferulate.     

Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

5'-Nucleotidase activity in liver homogenates of rats treated with CCl4, colchicine, cycloheximide, emetine, ethanol, ethionine and 5-fluorotryptophan

5'-Nucleotidase activity an enzyme marker of the plasma membranes, increases in female rat liver homogenates following ethionine administration, while homogenates from males show no changes. Treatment with CCl4, colchicine, cycloheximide, emetine, ethanol and 5-fluorotryptophan does not significantly modify the 5'-nucleotidase activity of liver homogenates of either female or male rats.     

Age variation in the increase of hypothalamic and brain stem contents of phenylethanolamine m-octopamine and p-octopamine in spontaneously hypertensive rats (SH Kyoto).

Phenylethanolamine, m-octopamine and p-octopamine contents were determined as a function of age in the hypothalamus and brain stem of spontaneously hypertensive rats and controls Wistar Kyoto. In hypothalamus, the content of the 3 amines was 2--4-fold greater for the SH rats. In the brain stem, the phenylethanolamine and p-octopamine contents were 2--3-fold greater in SH rats but 5--6-fold higher in the case of m-octopamine. The difference appears at 3 weeks and correlates the blood pressure with the increase of age. The significance of these findings is discussed.