Enhancement of ethanol-induced sleep by whole oil of nutmeg

In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1--4 g/kg), particularly deep sleep. Iproniazid (50-400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.     

Sperm enzyme activity analysis in individual sperm for detection of heritable mutations in mammals

Summary Male mice were injected i.p. with 2.5 mg/kg mitomycin C, 100 mg/kg ethyl nitrosourea or saline and mated with untreated virgin females five weeks later. Sperm from 64 of the F₁ male progeny were analyzed histochemically for acrosin, succinic dehydrogenase and alpha-glycerophosphate dehydrogenase activity. The frequency of F₁ males with sub-normal sperm enzyme activity was significantly higher among progeny from treated males than in controls. These results show that analysis of sperm enzyme activity in F₁ males is a practical method for detection of transmitted mutations induced in a treated parent.We gratefully acknowledge USPHS, NIEHS grant 1 RO1 ES02607-02 and technical assistance by G. M. Oldford.     

Melatonin modulates apomorphine-induced rotational behaviour

Summary Prior melatonin administration (1 and 10 mg/kg b.wt) causes a significant reduction in apomorphine (1 mg/kg b.wt) induced rotational behaviour in both 6-hydroxydopamine and quinolinic acid lesioned rats.     

Induction of microsomal drug-metabolizing enzymes caused by hexobarbital.

Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/kg,then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases. Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.     

Induction of microsomal drug-metabolizing enzymes caused by hexobarbital

Summary Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/ kg, then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases.—Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.     

The effects of naloxone on the analgesic activities of general anaesthetics

Summary Inhaled concentrations of nitrous oxide (80%), halothane (0.5%), trichloroethylene (0.5%) and s.c. ethanol (1 ml/kg) caused similar degrees of excitation and ataxia in mice. Nitrous oxide, tricholoroethylene and ethanol caused analgesia (hot plate and writhing tests), but only that caused by nitrous oxide was antagonized by naloxone (20 mg/kg). Halothane lacked analgesic activity.     

Enhancement of ethanol-induced sleep by whole oil of nutmeg

Summary In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1–4 g/kg), particularly deep sleep. Inproniazid (50–400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.Acknowledgments. The authors would like to thank Mr E.J. Spellman of Frische-D & O for supplying the oil of nutmeg and Mrs N. Sherry for secretarial and editorial assistance.     

Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n=16), 75 (n=18) or 8000 mg (n=18) α-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10 mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective to protect from endotoxin-induced hepatic microvascular dysfunction. Received 7 November 1996; received after revision 30 December 1996; accepted 20 January 1997     

Alpha adrenergic control of growth hormone in adult male rats.

Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 mug/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central alpha-adrenergic stimulation resulting in an increased GH secretion is one important mechanism in the regulation of this hormone in the rat.     

Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats

Treatment 20 min beforehand with an inhibitor of nitric oxide (NO) synthesis, N^W-nitro-l-arginine methyl ester (L-NAME) (12.5, 25, 50 or 100 mg/kg, s.c.), dose-dependently intensified gastric glandular mucosal ulceration produced by cold-restraint stress. Hexamethonium (20 mg/kg) or atropine (1 mg/kg) pretreatment s.c. 20 min before stress strongly antagonised stress-evoked ulceration, as well as the ulcer-potentiating effects of L-NAME when either cholinoceptor antagonist was given concurrently with the NO inhibitor. Stress-induced mast cell degranulation was not worsened by L-NAME pretreatment. The findings suggest that NO could confer partial protection against stress-induced gastric ulcer formation; its activity is triggered off by the ulcerogenic mechanism of stress.     

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.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Influence of adrenergic blocking agents upon morphine and catecholamine analgesic effect

Resumen Las catecolaminas adrenalina (0,25 y 0,5 mg/kg) noradrenalina (0,5 y 1 mg/kg) e isoproterenol (4 y 8 mg/kg) producen efecto analgésico significativo en lauchas. También aumentan (adrenalina 0,25 mg/kg, noradrenalina 0,5 mg/kg e isoproterenol 4 mg/kg) el efecto analgésico de pequeñas dosis de morfina (1 mg/kg). El bloqueador -adrenérgico dihidroergotamina (4 mg/kg) no influencia substancialmente estas acciones, pero el bloquente-adrenérgico propranolol (1 mg/kg) bloquea los efectos analgésicos de la morfina, adrenalina e isoproterenol, no siendo tan efectivo contra la noradrenalina. Se deduce que debe existir un compromiso de receptores-adrenérgicos en el mecanismo de los efectos analgésicos de las catecolaminas y también de la morfina.

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Fellow of the Consejo de Investigaciones Cientificas y Técnicas.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50-200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Effect of desipramine on the contents of some free amino acids of mouse brain

I.p. injections of desipramine-HCl (100 mg/kg) produced decreases in the contents of several amino acids of mouse brain after 1 h. Using a 10-100 mg/kg range of doses, these effects appeared to be dose-dependent for alpha-alanine and aspartate. These changes may be due, in part, to a decrease in cerebral oxidative metabolism (Krebs cycle activity) which occurs secondarily to desipramine-induced hypothermia.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

Summary The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50–200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Thermogenic effects of thyrotrophin-releasing hormone and its analogues in the rat

Acute or chronic injection of RX 77,368 (a TRH analogue; 1 mg/kg s.c.) stimulated oxygen consumption (VO2) and brown adipose tissue activity in the rat, and decreased weight gain. Other TRH analogues (CG 3509, RGH 2202) and TRH itself also stimulated VO2. These thermogenic actions are probably mediated centrally by stimulation of sympathetic outflow to brown fat.     

Dämpfung des Kältezitterns durch Pentobarbital und Pethidin bei Ratten

Summary In rats, shivering was induced by cooling. Shivering started at 36.6°C in unanaesthetized rats and at 36.0°C in animals with light pentobarbital anaesthesia (5 mg/kg i.V.). Pethidine (2 mg/kg) lowered the onset of shivering in unanaesthetized rats to 35.3 °C and in anaesthetized animals to 33.0°C. The results suggest that the effect of pethidine upon shivering is potentiated by pentobarbital.     

Alpha adrenergic control of growth hormone in adult male rats

Summary Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 g/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central -adrenergic stimulation resulting in an increased GH secretion is one importantmechanism in the regulation of this hormone in the rat.     

Influence of flupirtine, a novel nonopioid analgesic agent on somatosensory evoked potentials in rats.

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID50-values of 5.4 mg/kg (2.6-9.3 mg/kg) and 7.9 mg/kg (3.9-13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.