Search PubMed⌕ Search

Biomedical subjects

I K Ho

Publications and source records attributed to I K Ho.

At least 181 records · Page 10Linked to original sources
PubMed1987

N,N'-diallylpentobarbital: antagonism of barbital in mice and rats.

N,N'-Diallylpentobarbital (DAPB) antagonized barbital (B)-induced sleep in mice and rats. DAPB [80 mg/kg, intraperitoneal (i.p.)] reduced the barbital (350 mg/kg, i.p.)-induced sleeping time to 40% of the control in mice. Twenty, 40 and 80 mg/kg, i.p. of DAPB reduced barbital-induced sleeping time when administered 60 min prior to injection of barbital. DAPB (80 mg/kg, i.p.) also shortened barbital (250 mg/kg, i.p.)-induced sleeping time to about 70% of the control in rats. The result indicates that DAPB is an antagonist against hypnotic activity of barbital.

Animals↗
PubMed1987

Quantitative assessment of tolerance development to diisopropylfluorophosphate.

Rats were treated with diisopropylfluorophosphate (DFP) acutely or daily for 14 days. The quantitative assessment of tolerance development after a challenge dose of DFP, 2 mg/kg, was studied. The subacutely-treated rats developed tolerance to DFP-induced tremors. However, the severity of tremors in DFP-tolerant animals was not significantly different from that of the controls after the challenge dose of DFP was administered. Hind-limb abduction was significantly lower in the subacutely-treated group than in the acutely-treated group. The recovery of body weights in subacutely-treated rats (3.5%/day) was significantly higher than that in acutely-treated rats (2.0%/day). The consummatory behaviors (food and water consumption) recovered faster in subacutely-treated rats than in the acutely-treated group. Body temperatures were decreased to the same extent in both groups, but the subacutely-treated group recovered faster. The total mortality was significantly lower in subacutely-treated rats (10%) than in acutely-treated rats (35%). The results further substantiate the finding that tolerance develops to various DFP-induced signs of toxicity.

Animals↗
PubMed1987

Effects of cold stress on brain regional calcium content in rats and mice.

The calcium levels of striatum, cerebellum, cortex, medulla and diencephalon from rat brain were significantly reduced after 30 minutes of cold exposure at 8 degrees C even though body temperatures were no different from pre-cold exposure values. Calcium content remained significantly depressed in striatum, cerebellum and diencephalon after 2 hours of cold exposure, at which time body temperatures were significantly depressed. A similar effect of short-term cold stress on calcium content in these brain regions from mice was observed. These results are consistent with a role of calcium in the maintenance of temperature and in adaptive responses to cold environments.

Animals↗
PubMed1987

N-substituted oxopyrimidines and nucleosides: structure-activity relationship for hypnotic activity as central nervous system depressant.

N3-Benzyluridine (3-(phenylmethyl)-1-beta-D-ribofuranosyluracil) (1f) and its related compounds were synthesized and evaluated for hypnotic activity as central depressants. The primary structural modification has been carried out at the N3 position of the pyrimidine ring in uridine. N3-Benzyl-substituted uridine exhibited hypnotic activity as well as pentobarbital (PB) induced sleep effect on mice when administered by intracerebroventricular (icv) injection. From this result, the secondary modification was performed, namely, converting the benzyl group into a benzyl analogous group. These compounds also showed hypnotic activity, but their intensities were varied. Thirdly, changing the sugar moiety was investigated; however, it was found to be necessary for hypnotic activity. In general, introduction of benzyl analogous groups at the N3 position of uridine increased the hypnotic activity, and modification of the sugar moiety decreased the activity. Intravenous (iv) administration failed to indicate hypnotic activity in most of the compounds tested. However, modified sugars such as 2',3',5'-tri-O-methyl or -acetyl derivatives of 1f elicited hypnotic activity by iv injection. The majority of compounds were found to show potentiation of the PB-induced sleep, and their effects were in parallel with the hypnotic activity. The result clearly indicates that the benzyl group and beta-D-ribofuranosyl, at the N3 and N1 positions, respectively, are necessary for hypnotic activity. The critical portion of the chemical structure for both effects appears to be the uridine moiety.

Animals↗
PubMed1987

Sensitivity difference to hepatotoxicity of cocaine in spontaneously hypertensive and Wistar Kyoto rats.

Experiments were conducted to determine the hepatic damage of cocaine in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats in terms of serum glutamic-oxaloacetic transaminase (SGOT) activity, liver weight/body weight ratio and hepatic microsomal enzyme activity, i.e., N-demethylase activity or UDP-glucuronyltransferase (GT) activity. In subacute experiments, 2, 4 and 10 daily cocaine treatments elevated the level of SGOT activity and reduced the liver weight/body weight ratio in SHR rats. The ethylmorphine N-demethylase activity and the cocaine N-demethylase activity in SHR rats were significantly greater (31% and 26%, respectively) than those in WKY rats. Ten daily treatments with cocaine diminished the ethyl morphine N-demethylase activity and the cocaine N-demethylase activity in SHR and WKY rats. However, attenuation of 4-nitrophenol GT activity was only observed in SHR rats. In acute experiments, a single dose of cocaine, 40 mg/kg, elevated the SGOT activity in SHR rats and reduced the 4-nitrophenol GT activity in SHR rats, but it did not affect the activities of SGOT and 4-nitrophenol GT in WKY rats. A higher dose of cocaine, 60 mg/kg, elevated the SGOT activity and reduced cocaine N-demethylase activity and 4-nitrophenol GT activity in both SHR and WKY rats. The present studies suggest that N-demethylation of cocaine plays an important role in the hepatotoxicity of cocaine in animals.

Animals↗
PubMed1987

Mechanism of N,N'-diallylpentobarbital potentiation of pentobarbital-induced sleep in mice.

Potentiation mechanism of pentobarbital (PB)-induced sleep by N,N'-diallylpentobarbital (DAPB) was studied in mice. DAPB significantly prolonged the PB [40 mg/kg, intraperitoneal (i.p.)]-induced sleeping time by two routes of administration [intravenous (i.v.) and intracerebroventricular (i.c.v.)], nevertheless DAPB alone was devoid of hypnotic activity even by both routes of administration (i.v. and i.c.v.). In addition, DAPB (160 and 320 mg/kg, i.p.) significantly prolonged the sleeping time induced by i.c.v. injection of PB (200 micrograms/mouse). The brain PB half-life (T1/2) of DAPB (80 mg/kg, i.p.) treated group (9.0 h) was 13-fold longer than that of the control (0.7 h). The plasma PB half-life (T1/2) of DAPB treated group (15.2 h) was longer than that of the control (0.6 h). Moreover, DAPB significantly decreased the activities of ethylmorphine (EM) N-demethylase and aniline hydroxylase, and the content of cytochrome P-450 in mouse liver microsomes. The inhibitory effect of DAPB (40 mg/kg, i.p.) on the mouse hepatic drug-metabolizing enzymes was shown til 6 h after administration. DAPB exhibited non-competitive inhibition on the EM N-demethylase activity in vitro. These results indicate that DAPB prolongs the PB-induced sleeping time by both its depressant action to the central nervous system (CNS) and inhibitory effect on the hepatic drug-metabolizing enzymes.

Animals↗
PubMed1986

The role of dopamine in behavioral supersensitivity to muscarinic antagonists following cholinesterase inhibition.

The role of brain dopamine (DA) in the enhancement of muscarinic antagonist-induced hyperactivity was investigated. The effects of atropine and scopolamine on the concentrations of DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), following DFP administration were determined. In control animals, atropine and scopolamine decreased the concentration of DA and increased the ratios of DOPAC/DA and HVA/DA in the striatum, but not in the N. accumbens - T. olfactorium (mesolimbic) area. Following a single dose of DFP, the two antimuscarinic drugs caused decreases of DA and further increases of the above ratios in both brain regions. However, following repeated DFP treatment for 2 weeks, these antimuscarinic drug-induced changes were observed only in the mesolimbic area, but not in the striatum. It is suggested that an increased DA turnover, indicated by elevated DOPAC/DA and HVA/DA ratios, underlies the muscarinic antagonist-induced hyperactivity. The well-known occurrence of muscarinic receptor down-regulation after DFP administration, could be responsible for the enhancement of the actions of muscarinic antagonists in DFP-treated animals. The observed differential effect on DA turnover in the two broad areas may involve both muscarinic and DA receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Lack of effect of dynorphin on consummatory behaviors in obese and normal rats.

The possible role of dynorphin, an endogenous opioid peptide, in the regulation of appetite was studied in male genetically-obese (Zucker) rats and their litter mates of normal weight. Eighteen pairs were divided into 3 treatment groups: control, acutely dynorphin-treated (5 mg/rat), and implanted with Alzet mini-osmotic pumps containing 2 mg dynorphin to be delivered at a rate of 10 micrograms/hr. Body weights and food and water consumption were determined daily for 7 days. Body weights were not significantly changed from initial values for any treatment group. Food and water consumption per 24 hours were generally the same for obese rats and their normal littermates, but in terms of consumption per 100 g body weight, the obese rats generally consumed less food and water. Neither acute nor continuous dynorphin administration affected consummatory levels.

Animals↗
PubMed1986

Correlation of muscarinic receptor density and acetylcholinesterase activity in repeated DFP-treated rats after the termination of DFP administration.

Following chronic exposure to DFP, both AChE activity and muscarinic receptor density were markedly depressed in the rat striatum. The rate of recovery of AChE activity was 5.2% per day within 7 days, while the density of muscarinic receptor recovered at the rate of 1.94% per day. The correlation between 2 parameters was very high (R = 0.99). Thus, it is suggested that the muscarinic receptor density was intimately related to AChE activity.

Acetylcholinesterase↗
PubMed1986

Selective inhibitory effect of organophosphates on UDP-glucuronyl transferase activities in rat liver microsomes.

The effects of acute and subacute administration of diisopropylfluorophosphate (DFP) and acute administration of Soman, Sarin and Tabun on UDP-glucuronyltransferase (GT) activity towards 4-nitrophenol, 4-methylumbelliferone, phenolphthalein and testosterone in rat liver microsomes were investigated. Twenty-four hours after a single injection of DFP, the activity of GT towards 4-nitrophenol and 4-methylumbelliferone was inhibited, and the inhibitory effect continued for 3 days. The activity had recovered by 7 days after injection. The activity of GT towards phenolphthalein and testosterone was not affected at any time after injection. Soman, Sarin and Tabun showed the same effect as DFP after a single injection. After daily DFP injections, the activity of GT towards 4-nitrophenol and 4-methylumbelliferone was decreased to the same level as found following acute treatment with DFP. The in vitro addition of DFP to liver microsomes did not affect GT activity towards 4-nitrophenol. It is suggested that these changes are not due to a direct effect of DFP. Furthermore, the effects of two enzyme inducers on GT activity in the presence and absence of DFP were investigated. In the 3-methylcholanthrene (MC) pretreatment group, DFP inhibited only the GT activity towards 4-nitrophenol and 4-methylumbelliferone. On the other hand, in the phenobarbital (PB) pretreatment group, DFP did not inhibit the GT activity towards 4-nitrophenol and 4-methylumbelliferone. It was also demonstrated that MC pretreatment increased the mortality in the DFP-treated rats but that PB pretreatment suppressed it. These results suggest that DFP and other organophosphorus agents may be useful agents for studies on the heterogeneity of GT.

Androsterone↗
PubMed1986

In vivo and in vitro synthesis, release, and uptake of [3-H]-dopamine in mouse striatal slices after in vivo exposure to chlordecone.

Effects of treatment of mice with chlordecone (25 mg/kg/d) on striatal dopaminergic activities such as synthesis, turnover, uptake, and release were investigated in vivo and in vitro. In mice receiving chlordecone for five days, there were no significant changes in in vivo dopamine (DA) synthesis and turnover in striatum and in vitro [3-H]-dopamine uptake and K+-stimulated [3-H]-dopamine release in striatal slices. In mice receiving chlordecone for eight days, the in vivo synthesis of [3-H]-dopamine from [3-H]-tyrosine in striatum was slightly inhibited and the in vitro [3-H]-dopamine synthesis in striatal slices was significantly decreased. Furthermore, both uptake and K+-stimulated release of [3-H]-dopamine from striatal slices were significantly reduced. The turnover rate of newly synthesized [3-H]-dopamine from [3-H]-tyrosine in striatal slices was unchanged after eight consecutive days of chlordecone administration. These results suggest that chlordecone may cause impairments in pre- and/or postsynaptic membranes of dopaminergic neurons which modulate motor function.

Animals↗
PubMed1986

The efficacy of alpha-ketoglutaric acid in the antagonism of cyanide intoxication.

It has been reported that compounds containing carbonyl groups can readily react with cyanide. Pyruvic acid, an alpha-ketocarboxylic acid, has been shown to antagonize the lethal effects of cyanide. It is suggested that its mechanism of action rests in its ability to react with or "bind" cyanide. In this study, alpha-ketoglutaric acid, also an alpha-ketocarboxylic acid, was evaluated for its ability to counteract the lethal effects of cyanide. alpha-Ketoglutaric acid increased the LD50 value of cyanide (6.7 mg/kg) by a factor of five, a value statistically equivalent to that ascertained in mice pretreated with sodium thiosulfate and sodium nitrite. The combination of alpha-ketoglutaric acid and sodium thiosulfate increased the LD50 value of cyanide to 101 mg/kg. Addition of sodium nitrite to the alpha-ketoglutaric acid/sodium thiosulfate regimen increased the LD50 value of cyanide to 119 mg/kg. Unlike sodium nitrite, no induction of methemoglobin formation was observed with alpha-ketoglutaric acid pretreatment. It is apparent from these studies that the administration of alpha-ketoglutaric acid in conjunction with sodium thiosulfate resulted in fewer animal deaths than sodium nitrite and sodium thiosulfate without the dangerous formation of methemoglobin.

Animals↗
PubMed1986

Effects of maturation and aging on calmodulin and calmodulin-regulated enzymes in various regions of mouse brain.

Components of the calmodulin system (i.e., calmodulin levels and activities of the following calmodulin-dependent enzymes: Ca2+ + Mg2+-ATPase, adenylate and guanylate cyclases, cyclic AMP and cyclic GMP phosphodiesterases, and Ca2+-dependent protein kinase were studied in the following brain regions from immature (25-day-old), mature (3-month-old) and aged (22-month-old) mice: striatum, cortex, cerebellum, diencephalon and medulla + pons. Both maturation and advanced aging were associated with significant changes in calmodulin content and in enzyme activities. The study provides evidence for important changes in the activity of this fundamental cell regulatory system in the brain during the processes of maturation and aging.

Aging↗
PubMed1986

Differences in morphine-induced antinociception and locomotor activity in mature adult and aged mice.

Mature adult (3-6 months old) and aged (24-27 months old) male ICR mice were injected with 10 to 100 mg/kg morphine, SC. The ED50 values for locomotor behavior representing 5 times control activity were 7.5 mg/kg for aged mice and 17.8 mg/kg for the mature adults. There were striking age- and dose-dependent differences in both intensities and durations of morphine-induced locomotor activity. The ED50 values for antinociception 1 hour after morphine administration were 70 mg/kg for the aged mice and 13 mg/kg for the mature adults. One hour after injecting 30 and 100 mg/kg morphine tagged with 3H-morphine, 0.13 and 0.14 percent of the doses appeared in brains of aged and mature adult mice, respectively. Distribution of morphine among brain regions was the same for both age groups. The results suggest that the differences in response to morphine by the two age groups were due to age-related differences in affinities, numbers and/or functioning of opioid receptors and not to pharmacokinetic differences.

Aging↗
PubMed1986

Relationship between the neurotoxicities of Soman, Sarin and Tabun, and acetylcholinesterase inhibition.

Acetylcholinesterase (AChE)-induced chewing movements, tremors, convulsions and hind limb abduction at doses of 50-85% LD50 in rats were monitored in order to determine whether the severity of these different signs would correlate with brain AChE levels and the time course of such a relationship. 30 min after subcutaneous (s.c.) injection of Soman, the intensities of toxic signs were significantly correlated with the degree of striatal AChE inhibition. In the case of Sarin, the corresponding r-values were not significant except for tremors. For Tabun-induced chewing, tremor and hind-limb abduction, the r-values were significant. The neurotoxicity was most intense between 15 min to 2 h after treatment, but at 2 or 6 h, the r-values were well below 0.5. The inhibition of brain AChE was maximal by 30 min and was still high at 24 h.

Animals↗
PubMed1986

Hypersensitivity to antimuscarinic agents following brief exposure to Soman and Sarin.

Behavioral responses to atropine in rats exposed to the potent anticholinesterase agents Soman and Sarin were studied. Atropine itself produced limb-shakes and certain stereotyped activities, in a dose-dependent manner. The neurotoxicity elicited by Soman and Sarin was antagonized by atropine, while at the same time the responses induced by the latter were attenuated. In contrast, where rats were challenged with atropine 6-72 h after giving single doses of Soman or Sarin, the limb-shake myoclonus was markedly enhanced. The atropine-induced stereotypies were not, however, significantly affected, except for an increase seen at 24 h after Sarin treatment. Repeated treatment with Soman for 3 wk also led to similar supersensitivity of atropine-induced responses. The peripheral muscarinic receptor antagonist, methylatropine, produced no such hyperactivity on its own or at any time after anticholinesterase exposure. The rapid occurrence of hypersensitivity to antimuscarinic compounds following exposure to these anticholinesterases, therefore, suggests the need for observation of subjects who are poisoned with such agents and treated with antimuscarinics, for adverse reactions such as myoclonus during the critically sensitive period, especially if repeated antimuscarinic therapy is carried out.

Animals↗