L-arginine and pancreatic islet blood flow in anesthetized rats

The aim of the present study was to see if L-arginine, which induces insulin release and is a precursor of the endothelial-derived relaxing factor nitric oxide, affects whole pancreatic and/or islet blood flow. For this purpose, anesthetized male Sprague-Dawley rats were injected intravenously with either saline or L-arginine (25, 100 or 250 mg/kg body weight). All doses of arginine caused a slight increase in blood glucose concentration, while the highest dose (250 mg/kg body weight) also increased insulin concentration. However, no changes in either mean arterial blood pressure, whole pancreatic or islet blood flow could be discerned with any of the doses of arginine used. It is concluded that insulin release is not necessarily associated with an increased islet blood perfusion.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Lack of effect of butylated hydroxytoluene on dimethylhydrazine-induced colon carcinogenesis in rats.

Rats were given 6600 ppm of butylated hydroxytoluene (BHT) in the diet along with 10 weekly oral doses of dimethylhydrazine (DMH, 30 MG/KG). The incidence and mean number of colonic tumors produced were similar to that of rats given DMH alone. Thus, BHT did not provide any protective effect against colon carcinogenesis.     

The dopamine autoreceptor agonist B-HT 920 markedly stimulates sexual behavior in male rats

Summary B-HT 920, a selective agonist at dopamine (DA) autoreceptors, strongly increased the incidence of penile erections (PE) in male rats, an effect which was dose-related and antagonized by haloperidol. B-HT 920 at 100 and 200 g/kg i.p. significantly altered the copulatory pattern of sexually active male rats, reducing the number of mounts and intromissions as well as the latency to the first ejaculation, a stimulant effect which was confirmed in sluggish males at a dose of 100 g/kg.     

Stimulation of gastric secretion by prostaglandin F2 alpha in rats.

In rats with chronic gastric fistulas, prostaglandin F2 alpha stimulated the gastric acid secretion in graded doses of 50, 100, 200 and 400 microgram/kg b.wt, while higher doses above 1 mg/kg b.wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E1 could not be altered or modified by subsequent treatment of prostaglandin F2 alpha, while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.     

外源性干细胞因子对糖尿病胃轻瘫大鼠胃窦Cajal细胞的影响

目的探讨外源性干细胞因子（SCF）能否改善糖尿病胃轻瘫（DGP）大鼠胃窦Cajal细胞（ICC）的异常病变。方法sD大鼠随机分为实验组和对照组，实验组腹腔注射链脲佐菌素（STZ）50mg／kg并高糖高脂饲料不规律喂养构建DGP模型，对照组腹腔注射等量生理盐水并普通饲料规律喂养。成模后随机分为糖尿病组（DM组）、糖尿病＋外源性干细胞因子治疗组（DM＋SCF组）；DM＋SCF纽腹腔注射SCF0．4ug／（kg·d），共15天，对照组和DM纽每天腹腔注射等量的磷酸盐缓冲液（pH=7．4）。RT-PCR、Wester Dblot检测胃窦组织中SCF及c—kit的mRNA及蛋白表达；免疫组化、透射电镜观察胃窦组织中Cajal细胞的变化。结果DM组大鼠胃窦组织SCF及c—kit的mRNA及蛋白表达下降，Cajal细胞数量减少，细胞内线粒体肿胀、内质网扩张；予外源性SCF干预后，胃窦组织中SCF及C—kjf的mRNA及蛋白表达上调，caial细胞数量增多、超微结构明显改善。结论外源性SCF能在一定程度上改善或逆转糖尿病胃轻瘫大鼠胃窦Cajal细胞的异常病变：     

外源性干细胞因子对糖尿病胃轻瘫大鼠胃动力的影响

目的 探讨外源性干细胞子(Stem cell factor,SCF)对糖尿病胃轻瘫大鼠(diabetic gastroparesis,DGP)胃电及胃阻抗的影响.方法 30只SD雄性大鼠随机分为实验组和对照组,实验组采用一次性腹腔注射链脲佐菌素(streptozotocin,STZ) 50 mg/kg并高糖高脂饲料喂食建立DGP模型;成模后随机分为糖尿病组(DM组,n=8)、糖尿病+外源性干细胞因子治疗组(DM+ SCF组,n=8);DM+ SCF组腹腔注射SCF 0.4 ug/(kg·d),共15天,对照组和DM组每天腹腔注射等量的磷酸盐缓冲液(pH=7.4).阻抗式胃动力系统检测大鼠胃动力和同步胃电,透射电镜观察胃窦平滑肌细胞超微结构的变化.结果 DM组大鼠胃电节律紊乱,胃电主功率百分比较对照组显著降低(P＜0.01);DM组大鼠阻抗主功率百分比明显降低(P＜0.01),阻抗胃动过缓功率百分比明显升高(P＜0.01);DM大鼠予SCF干预后,胃电、胃阻抗主功率百分比均有所改善(p ＜0.01;P＜0.05);DM组大鼠胃窦平滑肌细胞胞核肿胀、肌浆网、内质网扩张,部分细胞胞质内细胞器溶解、消失;DM组大鼠予SCF干预后胃窦平滑肌细胞超微结构改善,电镜下仅见平滑肌细胞胞核轻度肿胀,密斑、密体、肌丝稍减少,余细胞器未见明显异常改变.结论 外源性SCF能显著改善DGP大鼠的胃电,并能部分改善其胃蠕动,其机制与胃窦平滑肌结构的改善有关.     

Valproic acid attenuates inflammation in experimental autoimmune neuritis

Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA (300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed mRNA levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and IL-17 in the lymph nodes of EAN rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3⁺ cells were increased but IL-17⁺ cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting that VPA could be a potent candidate for treatment of autoimmune neuropathies.     

The effect of bradykinin on blood flow and heat production in the myocardium

Résumé En utilisant comme méthode la calorimétrie interne, nous avons montré que la bradykinine synthétique abaisse la résistance vasculaire dans le myocarde du lapin, du chat et du singe, même à doses aussi réduites que 0,05 µg/kg. Des doses plus fortes (5 µg/kg) augmentent aussi l'activité métabolique du myocarde.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Interleukin-8 is a Cyclosporin A binding protein

Inflammatory immune reactions occur during transplant rejections and autoimmune diseases. Such reactions are mediated by cytokines, including interleukin-8 (IL-8). Cyclosporin A (CsA) exerts immunosuppressive activities^1,2 by binding to immunoregulatory proteins termed cyclophilins³. The anti-inflammatory effects of CsA are still not fully understood. Searching for novel neutrophil-activating proteins, we observed that an antiserum against human recombinant Interleukin-8 (IL-8) cross-reacted with cyclophilins in Western blots. Furthermore, native IL-8 was found to specifically bind CsA, whereas biologically inactive analogs of CsA were not bound by IL-8. Putative binding sites for CsA on IL-8 could be identified on the basis of structural similarities between IL-8 and cyclophilin. However, IL-8 lacks peptidyl-prolyl-isomerase (PPlase) enzyme activity, which is regarded as a characteristic of cyclophilins^4,5,6. We conclude that the specific binding of CsA to IL-8 may explain some of the anti-inflammatory effects of CsA. IL-8 may be a novel member of the cyclophilins lacking PPlase activity.     

Lack of pressor effect of dopamine in the pentobarbital-anesthetized rat

The blood pressure and heart rate responses to intravenous dopamine infusion at 2.5, 5.0 and 10.0 micrograms.min-1 X 100 g-1 were studied in conscious and pentobarbital-anesthetized Sprague-Dawley rats. In the conscious rats, dopamine caused a significant dose-related increase in the mean arterial blood pressure which was abolished in the anesthetized rats. The heart rate increased significantly only at the highest dose infused. The responses to equipressor doses of noradrenaline (40 ng.min-1 X 100 g-1) and phenylephrine (1.0 micrograms.min-1 X 100 g-1) were also suppressed in the anesthetized rats. The results suggest that pentobarbital anesthesia depresses the blood pressure response to dopamine infusion in the rat through a depression of activation of alpha-adrenoceptors.     

The dopamine autoreceptor agonist B-HT 920 markedly stimulates sexual behavior in male rats

B-HT 920, a selective agonist at dopamine (DA) autoreceptors, strongly increased the incidence of penile erections (PE) in male rats, an effect which was dose-related and antagonized by haloperidol. B-HT 920 at 100 and 200 micrograms/kg i.p. significantly altered the copulatory pattern of sexually active male rats, reducing the number of mounts and intromissions as well as the latency to the first ejaculation, a stimulant effect which was confirmed in sluggish males at a dose of 100 micrograms/kg.     

Diurnal rhythm of ethanol metabolism in the rat

Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.     

The effect of melatonin on the formation of gastric stress lesions in rats

Summary Prior melatonin administration (1,5 and 10 mg/kg b. wt) causes a significant reduction in gastric ulceration induced in male rats by restraint immobilization in the presence of low temperatures.     

Liver steatogenic power of high doses of rifampicin in rats]

The possible induction of fatty liver by Rifampicin has been investigated by oral administration of two different doses (200 and 400 mg/kg/24 h) of this antibiotic for a period of 8 days to male and female Rats. The results obtained are more constant and more coherent in male than in female. It is the 400 mg/kg/24 h dose which is more effective, leading to an increase of lipids, triglycerides and cholesterol in the liver and a decrease of serum triglycerides. A dose-effect relationship may exist. These preliminary data lead us to believe that Rifampicin may inhibit the synthesis of the protein moiety of lipoproteins, such as alpha-Amanitin, which is also a RNA-polymerase inhibitor.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Summary Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2–4.9 g/g wet weight tissue while in the pancreas it was shown to be 15.2 g/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Absorption and biotransformation of L(+)-tartaric acid in rats

Summary Oral or parenteral doses of monosodium¹⁴C-L(+)-tartrate (400 mg/kg) are rapidly excreted by rats and a proportion completely metabolized to CO₂. The oral dose was well-absorbed.     

The effect of methaqualone on prenatal development in the rat

Methaqualone treatment of pregnant rats in doses of 100-200 mg/kg day produces resorption and a series of anomalies whose incidence increases with the dose-level employed.     

Histamine-induced hypotension modified by H1 and H2 antagonists in the monkey (Macaca mulatta).

Blocking H2 receptors with burimamide in the dose used (20 mg/kg) approximately doubles the amount of histamine needed to produce the same effect as seen when H1 antagonists (chlorpheniramine or mepyramine) are used alone. The Kz ratios for chlorpheniramine-chlorpheniramine plus burimamide are 117-204 and for mepyramine-mepyramine phus burimamide are 200-478. H1 and H2 receptors, in the monkey, when stimulated, both cause cardiovascular responses in the same direction.