Histamine as an extremely potent releaser of vasopressin in the rat

Summary Intraperitoneal and intraventricular injection of histamine induces a very fast and high elevation of vasopressin in rat plasma as determined by radioimmunoassay. The effects are dose and time related. The intraventricular injection is more effective with regard to time and dose than the intraperitoneal injection.     

Über die amindepletierende Wirkung verschiedener Digitaliskörper,ein Beitrag zur Aufklärung des Wirkungsmechanismus der Herzglykoside

Summary After i.v. injection of g-strophanthin, convallatoxin, digitoxin, digitoxigenin, digoxin and proscillaridin, dependent on the dose and time of application, we found a significant decrease of noradrenalin in the hearts of rats (about 50%).     

Variation in delayed hypersensitivity to methylated bovine serum albumin as as function of the dose and time of administration of cyclophosphamide]

The injection of Cy before immunization provokes an intensification of delayed-type hypersensitivity (DTH) to methylated bovine serum albumin (M-BSA) and a diminution of about 90% of the cell number in various lymphoid tissues. The relationship between these observations, the time of administration, the dose of injected Cy and the intensity of DTH reactions, allows us to formulate hypotheses concerning the physiological modulation of DTH.     

Time-dependence of estradiol effects on protein synthesis in the rat neurohypophysis.

The incorporation of 3H-leucine into neurohypophyseal proteins was measured in vitro, 24 h after the administration of a single dose of estradiol (0.3 mug) to castrated female rats. Estradiol treatment caused a significant increase of 3H-leucine incorporation into proteins of the posterior lobe. The effects of estradiol depended largely upon time injection. Rats injected at 06.00 h, i.e., at the end of the dark period exhibited a 74% increase in protein synthesis, whereas rat injected at 14.00 h, i.e., at the middle of the light period only showed a 30% of increase.     

Thrombozytose und Eosinopenie bei Ratten nach einmaliger 5-Oxytryptamininjektion

Summary After injection of a high dose of 5-hydroxytryptamine into rats, the blood reveals a strong increase of the blood platelets and a definite decrease of the eosinophiles. The maxima of increase and decrease are in temporal accordance.     

Irradiation of the head by 60Co opens the blood-brain barrier for drugs in rats

The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a 60Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of 3H2O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Fehlende immunogene Wirkung exogenen Insulins bei Hunden nach langsamer Adaptation an Insulin

Summary Subcutaneous injection of exogenous insulin always results in a production of antibodies against insulin. But after a slowly increased dose of insulin (a daily end dose of 3.5–4.2 U/kg) insulin antibodies could not be found in the serum of 2 dogs. This failure of immunogenic action of insulin is discussed as an induction of immunotolerance by the modus of initial antigen application.     

Cannabidiol and cannabinol in man

Résumé Le cannabidiol administré à dose de 100 mg par os et de 30 mg par injection i.v. fut inactif dans les sujets d'étude. Le cannabinol, à dose orale de 400 mg, le fut aussi. Ces constituants du cannabis ne contribuent donc pas à l'effet pharmacologique.     

Thrombozytose und Eosinophilie bei adrenalektomierten Ratten nach einmaliger 5-Hydroxytryptamininjektion

Summary In adrenalectomized rats, the injection of a single high dose of 5-hydroxytryptamin results, as in intact animals previously reported, in a strong increase of the number of platelets in the peripheral blood. The number of eosinophils, instead of decreasing, also rises. The maxima of increase are not in temporal accordance.     

Irradiation of the head by60Co opens the blood-brain barrier for drugs in rats

Summary The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a⁶⁰Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of³H₂O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide.

Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation.     

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.     

Thermoregulatory effects on the sheep of intracerebroventricular injections of L-glutamic acid

L-glutamic acid injected in doses of 200--1000 n moles . kg-1 into the cerebral ventricles of sheep had dose-dependent thermoregulatory effects: an increase in heat production and/or a decrease in respiratory frequency, and a rise in rectal temperature. A dose of 800 nmoles . kg-1 had effects comparable with those of a similar injection of 3 nmoles . kg-1 carbamylcholine.     

Beeinflussung der experimentellen allergischen encephalomyelitis durchε-aminocapronsäure

Summary The effect of -aminocaproic acid on EAE of rabbits was investigated. A partial inhibition, dependent on the dose administered by intravenous injection, can be proved. The formation of antibodies is not significantly impaired, whereas an inhibition of local granulomatosis is obvious. The results obtained can be interpreted as an inhibition of delayed immune reaction.     

Haemolymph ecdysteroids level following the injection of ecdysone or ecdysterone; its relation with tegument and midgut response inAeshna cyanea (Insecta,Odonata)

Summary The haemolymph ecdysteroid level after injection of ecdysone or ecdysterone inAeshna cyanea larvae has been determined by a radioimmunoassay method. The rate of excretion appears to be dependent on both the ecdysteroid injected and the time of injection. In case of ecdysone injection, the secretion of the epidermis cuticle and the differentiation of the imaginal midgut epithelium occur when the ecdysteroid level remains low for many days.     

Parenteral soya bean fat emulsions potentiate the hepatotoxicity of E. coli endotoxin in suckling rats

A dose of soy bean fat emulsion which was injected i.v. in suckling rats accumulated in the cells of liver parenchyma, both in hepatocytes and in reticuloendothelial cells. Subsequent i.p. injection of E. coli endotoxin was followed by extensive liver tissue necrosis and increased activities of serum aspartic and alanine aminotransferase. These signs of liver damage were markedly more pronounced than those observed after the administration of E. coli endotoxin only.     

Inhibited hormonal induction of hepatic phosphoenolpyruvate carboxykinase in poly I∶C treated mice,an endotoxin-like glucocorticoid antagonism

Summary Corticosteroid induction of mouse hepatic phosphoenolpyruvate carboxykinase was inhibited by prior injection of poly IC. Mice challenged with a lethal dose of endotoxin 4 h after administration of poly IC could not be protected by a concurrent injection of hydrocortisone.This investigation was supported by U. S. Public Health Service research grant No. AI-10087 from the National Institute of Allergy and Infectious Diseases.     

In vivo effect of sodium valproate on mouse liver

The in vivo effect of sodium valproate (SV) on the activity of uridine diphosphate glucuronosyltransferase (UDP-GT) and hepatotoxicity in the mouse liver was studied. Mice were injected intraperitoneally (IP) with SV at doses varying from 50 to 800 mg/kg per day, for six consecutive days (dose-response group) or at a standard dose of 300 mg/g per day for 2-10 days (time-response group), whereas the controls were injected with normal saline. Valproic acid levels had a positive correlation to the dose (P < 0.001) and duration of drug administration (P = 0.006). A gradual increase in UDP-GT activity was observed in doses of up to approximately 400 mg/kg per day, whereas in higher doses the enzyme activity gradually decreased. The time course of UDP-GT activity at the standard dose of 300 mg/kg per day increased progressively, with a maximum up to the sixth day and then had a gradual reduction. Hepatic necrosis (which was unrelated to the dose or the duration of drug administration) was found in 13% of the SV-treated animals and in none of the controls. We conclude that at an optimal dose (300-400 mg/kg per day) and at a time course of 6 days, SV causes liver UDP-GT induction, whereas in higher doses and longer duration of administration, UDP-GT activity is gradually reduced. SV also causes hepatotoxicity unrelated to dose and time course.     

Antitumor activity of the Isodon diterpenoids: structural requirements for the activity.

A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

基于人工鱼群算法的喷油系统断油电磁阀的优化设计

为合理选择和正确设计柴油自卸车喷油系统的断油电磁阀,根据电磁阀的结构特点,建立了在自卸车出现转速失控时喷油系统断油时间最短的目标函数。利用人工鱼群算法对断油电磁阀的阀芯质量、弹簧刚度、线圈匝数、工作气隙、阀芯举升高度进行优化,得出断油电磁阀的最佳动态响应参数,并利用HYDSIM分析了优化前后喷油系统的响应特性。结果表明：断油电磁阀参数优化后的喷油系统比优化前的系统的响应时间减小了5．59ms,能更有效地控制柴油机自卸车转速失控,明显提高柴油自卸车的运行安全和使用寿命．