Search PubMed⌕ Search

Biomedical subjects

I K Ho

Publications and source records attributed to I K Ho.

At least 199 records · Page 11Linked to original sources
PubMed1986

Acute effects of Soman, Sarin, and Tabun on cyclic nucleotide metabolism in rat striatum.

Rats were injected sc with 120 micrograms/kg Soman, 120 micrograms/kg Sarin or 240 micrograms/kg Tabun. At 15 min, 2 h, or 6 h after administration, animals were decapitated along with saline-treated controls, and striatal activities of nucleotide cyclases and phosphodiesterases and striatal cyclic nucleotide levels were determined. All three agents had two similar effects on rat striatal cyclic nucleotide systems: they all increased cyclic GMP levels 15 min after their administration, and they all decreased guanylate cyclase activity 2 h after administration. There were also some different effects elicited by these three organophosphorus compounds. Different effects of Soman and Sarin seem to be mainly due to their different potencies, which in turn influence the time course of their actions. Tabun is quite different from Soman and Sarin in several respects: it rarely causes convulsions at sub-lethal doses, it has no effects on striatal cyclic AMP levels, and it affects enzyme activities 6 h after its administration. These differences may be due to the presence of cyanide instead of fluoride in its structure: i.e., this may be responsible for the different effects of Tabun on striatal cyclic nucleotide systems, and perhaps other biochemical effects. These results also indicate that other neurotransmitter systems, in addition to the cholinergic system, may be involved in organophosphate-induced toxicity.

Adenylyl Cyclases↗
PubMed1986

Acute effects of soman, sarin, and tabun on microsomal and cytosolic components of the calmodulin system in rat striatum.

Two hours after administration of Soman (120 micrograms/kg, s.c.), Sarin (150 micrograms/kg, s.c.), or Tabun (240 micrograms/kg, s.c.), microsomes and cytosol were prepared from rat striata. Microsomal and cytosolic calmodulin (CaM) levels, microsomal adenylate and guanylate cyclase activities, protein kinase activities, and Ca2+ + Mg2+-ATPase activities were determined while cytosolic phosphodiesterase (PDE) activities were determined. CaM levels in both cell fractions were significantly increased by Soman and Sarin. Cyclic AMP-PDE and adenylate cyclase activities were decreased by Soman and Sarin. All three agents decreased activities of cyclic GMP-PDE and guanylate cyclase. Sarin and Tabun administration caused significant increases in microsomal protein kinase activity and none of the agents affected activity of divalent cation ATPases. The intensity of effects of the three organophosphates roughly paralleled their observed neurotoxic potencies. The results indicate that components of the CaM system are implicated as either causative or adaptive changes induced by these agents.

Adenylyl Cyclases↗
PubMed1986

Regional and subcellular calmodulin content of rat brain.

Calmodulin contents of cortex, cerebellum, striatum, diencephalon, and medulla + pons and of subcellular fractions of each region were determined by radioimmunoassay. The diencephalon had the highest level of calmodulin (48.87 +/- 4.56 micrograms/mg protein), whereas medulla + pons had the lowest level (8.01 +/- 0.84 micrograms/mg protein). In all brain regions, the mitochondrial fraction was richest in calmodulin (from 71 to 227 micrograms/mg protein) whereas other areas contained from 6 to 66 micrograms/mg protein.

Animals↗
PubMed1986

N,N'-diallylbarbital potentiation of drug-induced sleep and motor incoordination.

Pharmacological activities (hypnotic activity, anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures and motor incoordination) of N-allyl substituted derivatives of barbital (B) were investigated using mice. N-Monoallylbarbital (MAB) was found to possess more potent hypnotic activity [HD50 = 146(140-152)mg/kg, i.p.] and anticonvulsant activity [PTZ-ED50 = 25.1(18.1-34.8)mg/kg, i.p.] than the parent compound, barbital [HD50 = 179(153-209)mg/kg, i.p. and PTZ-ED50 = 27.7(25.5-30.1)mg/kg, i.p.]. N,N'-Diallylbarbital (DAB) was devoid of not only the hypnotic activity, but also of anticonvulsant activity and motor incoordination. The interactions of these N-allyl derivatives with various sedative-hypnotics [B, phenobarbital (PheB), amobarbital (AB), pentobarbital (PB), thiopental (TP) or diazepam (DZ)] were studied to characterize the antagonist or agonist properties of these N-allyl compounds. MAB (50-200 mg/kg, i.p.) showed a dose-dependent potentiation of B (200 mg/kg, i.p.)-induced sleep. DAB (150-300 mg/kg, i.p.) prolonged B-induced sleeping time, but its dose-response relationship was not clearly observed. Both compounds (150 mg/kg, i.p.) also significantly prolonged PheB-, AB-, PB- and TP-induced sleeping time. Further, DAB (40 mg/kg, i.p.) enhanced DZ-induced motor incoordination. These results indicate that MAB and DAB potentiate sedative-hypnotics responses in different manner, and that the mechanism of action may be due to their different effect, each other, on the central nervous system (CNS).

Animals↗
PubMed1986

Central effects of N-allyl,N'-methyl-barbital and N-allylmethyprylon in mice.

Pharmacological activities (hypnotic, anticonvulsant and convulsant activities, acute toxicity and pentobarbital (PB) synergism) of N-allyl,N'-methyl derivatives of barbiturates and related N-allyl substituted compounds were studied in mice. N-Allylhexobarbital (AHB), N-allylglutethimide (AGI) and N-allylmethyprylon (AMP) showed hypnotic activity. N-Allyl,N'-methyl derivatives of barbital (B), phenobarbital (PheB) and PB (AMB, AMPheB and AMPB), AHB and AMP exhibited anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures. AMP was the most potent agent among the allyl compounds tested in the protective effect against PTZ-induced seizures. N-Allyl, N'-methylallobarbital (AMAlloB) showed a weak convulsant activity at a dose of 640 mg/kg, i.p. All allyl compounds tested showed potentiation of the PB-induced sleep. AMB prolonged the PB-induced sleep 30-fold as compared with the control. These results indicate that AMB, AMP and the other N-allyl compounds possess some depressant effects on the central nervous system.

Allyl Compounds↗
PubMed1986

Neurotoxicity in rats following subchronic amiodarone treatment.

Rats were treated with amiodarone (20 mg/kg/day) up to 6 weeks and the neurotoxicity was assessed by determining changes in motor coordination, pain-threshold and rectal temperature every week during treatment. Body weight gain was decreased during amiodarone treatment and it was significant at and after 5 weeks. Food intake and water consumption were significantly reduced during treatment. After the first week of treatment with amiodarone, rats showed decreased ability to balance on horizontal rods. In the hot plate test (paw-lick), the amiodarone treated rats showed increased pain-thresholds throughout the treatment. Hypothermia was significant only at 6 weeks. These results show that amiodarone causes toxicity in rats and this model might be useful for further studies. Decreased motor-coordination, and increased pain-responding times may indicate development of peripheral neuropathy in addition to muscle weakness.

Amiodarone↗
PubMed1986

Central depressant activities of N3-allyluridine and N3-allylthymidine.

The pharmacological effects of N3-allyluridine (N3-AUd) and N3-allylthymidine (N3-ATd) on the central nervous system (CNS) were examined by intracerebroventricular (i.c.v.) administration in mice. Pentobarbital (PB)-induced sleep, diazepam (DZ)-induced motor incoordination and spontaneous activity were used as three indices of pharmacological tests. N3-AUd and N3-ATd as well as uridine (Ud) and thymidine (Td); 0.9 mg/mouse, i.c.v., were found to potentiate PB-induced sleep, and their effects were dose dependent. Time course test showed that the most potent effects of all compounds tested on PB-induced sleep were observed at 15 min after the i.c.v. injection of these compounds. N3-AUd and N3-ATd were greater than Ud and Td in PB-induced sleep prolongation. In the DZ-induced motor incoordination experiments, N3-AUd, N3-ATd and Td exerted synergistic effect, although these compounds did not possess the motor incoordination. All compounds decreased the spontaneous activity. These results show that both N3-allylated compounds have more directly depressant effects on the CNS than the parent compounds.

Animals↗
PubMed1985

Rapid induction of supersensitivity to muscarinic antagonists-induced motor excitation by continuous stimulation of cholinergic receptors.

Following single or repeated treatment with the irreversible anticholinesterase, DFP or, during infusion of the muscarinic receptor agonist, oxotremorine, and the reversible anticholinesterase physostigmine, effects of challenges with muscarinic antagonists were studied in rats. The antagonists, atropine, scopolamine, benztropine, orphenadrine and trihexyphenidyl induced, to a low degree, limb-shakes (myoclonus) and stereotyped behaviors in normal rats. However, within 24-72 hr after the above pretreatments, this myoclonus was significantly enhanced. The anticholinergic-stereotypies were also increased but only by severe cholinergic pretreatment and at a time later than that for the myoclonus. Myoclonus and stereotypies are known to be produced by treatments which directly enhance serotonergic and dopaminergic activities, respectively. It is suggested that during prolonged cholinergic stimulation, the cholinergic-monoaminergic balance in the brain can be altered depending upon the degree of stimulation. This could be responsible for the observed differential onset of changes in the anticholinergic-behavioral responses, which could, in turn, be mediated by different monoaminergic (serotonin and dopamine) systems.

Animals↗
PubMed1985

GABA in morphine analgesia and tolerance.

Drugs affecting various steps of GABA transmission exhibit analgesia in a variety of experimental models in animals; this analgesic response generally requires high doses of the drugs and does not appear to be opiate-like since the GABAergic analgesia is naloxone-insensitive and lacks dependence liability. The outcome of the analgesia response is variable when opiate and GABAergic drugs are administered together; however, directly acting GABA receptor stimulants and GABA-transaminase inhibitors generally enhance the analgesic effect of opiates. The development of newer GABAergic drugs with greater potency and specificity may offer an alternative to opiate analgesics. The results obtained over the years, on the possible involvement of the GABA system in morphine tolerance and dependence are equivocal. Studies on region-specific changes in opiate-GABA interaction as well as opiate-GABA-benzodiazepine interaction are needed to further elucidate the role of GABA on opiate system.

Analgesia↗
PubMed1985

Effects of aging and morphine administration on calmodulin and calmodulin-regulated enzymes in striata of mice.

Male ICR mice, young (25-days old), mature (3-months old), and old (22 months), were injected with morphine sulfate (10 mg/kg, s.c.) or were implanted with morphine pellets (75 mg). Controls received saline injections or placebo pellets. One hour after injections and 72 h after pellet implantations, the mice were decapitated and striatal regions were removed for the following analyses: calmodulin (CaM) levels via radioimmunoassay and activities of cyclic nucleotide phosphodiesterases, adenylate and guanylate cyclases, and Ca2+, Mg2+-ATPase. Acute morphine treatment produced the following: (1) increases in calmodulin levels in the young and old mice while having no effect on mature levels; (2) increases in activities of guanylate cyclase of mature mice while decreasing those of the old mice; (3) no effects on activity of adenylate cyclase; (4) decreased activity of cyclic AMP-phosphodiesterase in young mice only; (5) decreased activity of Ca2+, Mg2+-ATPase in the old mice only. The only changes found in striata from morphine-tolerant mice when compared with age-matched controls were elevations in cyclic GMP-phosphodiesterase activities in all three age groups. Differences in control values of the three age groups were as follows: CaM levels, mature greater than old greater than young; Ca2+, Mg2+-ATPase activity, old greater than mature-young. The results indicate age-induced changes in cellular regulation and biochemical responses to morphine.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Studies on low dose sub-acute administration of soman, sarin and tabun in the rat.

The effects of low-dose administration of the organophosphate cholinesterase inhibitors, soman, sarin and tabun, on growth rates over 85 days were studied in rats. Acetylcholinesterase (AChE) activity was determined in the striatum and the remainder of the brain 24 hrs following the last exposure to these agents. Further, the cumulative mortality of daily administration of several doses of soman, sarin and tabun for 25 days was studied. The animals treated with 25 micrograms/kg of soman or sarin for 85 days demonstrated reduced growth rates which returned to control levels after 30 days. The animals which received 50 micrograms/kg of sarin also grew at reduced rates which returned to control levels after 35 days, while the tabun-treated (100 micrograms/kg) animals required 38 days to return to control growth rates. The striatal AChE activity of the soman-treated group was reduced to 36% of control while the AChE activities of the high-dose sarin-treated group were reduced to 66% of control. The striatal AChE activity of the tabun-treated group was only 13% of control. It is suggested that growth rates may be used to monitor the development of tolerance to low-dose administration of organophosphate cholinesterase inhibitors.

Acetylcholinesterase↗
PubMed1985

The basal ganglia in chlordecone-induced neurotoxicity in the mouse.

This overview summarizes the available data concerning the neurotoxic effects of chlordecone on the basal ganglia in mice. Included are the effects of chlordecone on motor coordination, levels of biogenic amines, uptake of catecholamines and GABA, release of 3H-dopamine from striatal slices, newly synthesized dopamine, levels of dopamine metabolites in striatum, total and protein-bound Ca++ in discrete areas of brain, and distribution of chlordecone in discrete areas of brain. These data suggest that the basal ganglia may be the brain site at which chlordecone acts to produce its neurotoxic effects.

Animals↗
PubMed1985

Variability of neurotoxicity of and lack of tolerance to the anticholinesterases soman and sarin in the rat.

The neurotoxicity and lethality of Soman and Sarin, after single and repeated treatment at 50-60% of their LD50 doses in rats were investigated. Single treatment with Soman (100 micrograms/kg) and Sarin (120 micrograms/kg) produced severe tremors, convulsions and hypothermia, in some rats only, while the others did not show toxicity, i.e. an all or none effect. Soman and Sarin (100-120 micrograms/kg) caused, respectively, 89-93% and 26-48% inhibition of AChE at 6 hr and 56-68% and 17-39% inhibition at 24 h after single injections. Repeated treatment with Soman (90 micrograms/kg) and Sarin (100 micrograms/kg) at 4 day intervals caused variable incidences of neurotoxicity and increasing mortalities, and after ten injections the survival rates were 31 and 54%, and AChE inhibition was 86 and 75%, respectively. It is suggested, that the variable neurotoxicity of and the low tolerance to of these compounds are partly related to peripheral dispositional mechanisms. Furthermore, the profile of toxicity of these anticholinesterase agents should be differentiated from, but not generalized with, that of the other anticholinesterase organophosphates.

Animals↗
PubMed1985

The prolonging effect of N,N'-diallylpentobarbital on the drug-induced sleep and motor incoordination.

N-Allyl substituted derivatives of pentobarbital were prepared, and their pharmacological activities (hypnotic activity and anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures) were investigated with single intraperitoneal (i.p.) injection using mice. N-Monoallylpentobarbital (MAPB) was found to possess hypnotic activity [HD50 = 77.5(64.3-93.4) mg/kg, i.p.] and anticonvulsant activity [PTZ-ED50 = 23.5(14.2-38.9)mg/kg, i.p.]. N,N'-Diallylpentobarbital (DAPB) was devoid of not only the hypnotic activity of parent compound but also the anticonvulsant activity. The interaction of these N-allyl derivatives with barbiturates (pentobarbital (PB), barbital (B), phenobarbital (PheB), amobarbital (AB) and thiopental (TP] or diazepam (DZ) was further studied to characterize as antagonist or agonist. MAPB and DAPB (5-160mg/kg, i.p.) showed potent prolonging effect on PB-induced sleeping time and time of their peak effect was observed. The prolonging effects of these allyl compounds on PB-induced sleep were dose-dependent. Both compounds (80mg/kg, i.p.) also prolonged sleeping time induced by PheB, AB and TP. Although DAPB showed prolonging effect on B-induced sleep at a time interval 1 min, the compound shortened the sleeping time at 15 and 60 min. DAPB (5, 10 and 80mg/kg, i.p.) enhanced the DZ-induced motor incoordination.

Animals↗
PubMed1984

New rapid method of analysis of cefoxitin in serum and bone, by high-performance liquid chromatography.

A method for the extraction and quantification of cefoxitin in blood and bone samples is described in this paper. The procedure, which prepares biological material for reversed-phase high-performance liquid chromatographic analysis is convenient, rapid and reproducible. It also allows for use of cephalothin as an internal standard in measuring serum cefoxitin levels. Conventional extraction procedures, involving use of organic solvents, generally yield drug recoveries of 60-80%. Use of Baker--10 SPE disposable extraction columns allowed us to consistently obtain greater than 98% recovery of both cefoxitin and cephalothin. Methods for quantification of the extracted drugs include comparison of peak ratios (for serum) or peak heights (for bone) to first-order equations obtained from regression analyses.

Bone and Bones↗
PubMed1984

Attenuation of pharmacological effects and increased metabolism of phencyclidine in morphine tolerant mice.

Mice were used for a study of the interaction between morphine and phencyclidine (PCP) in relation to lethality, motor incoordination, locomotor activity and rearing, together with the half-life of PCP, following continuous administration of morphine by pellet (75 mg base) implantation for 72 h and after removal of the pellets for 6 and 24 h. PCP induced motor incoordination and suppressed locomotor activity and rearing; these effects were enhanced in morphine 'pellet-implanted' mice and were attenuated in morphine 'pellet-removed' groups. The enhancing effect of morphine on the PCP responses was attributable more to the presence of residual morphine than to the alterations in its disposition. The morphine-induced increase in locomotor activity and analgesia was attenuated in PCP (40 mg/kg per day i.p. for 5 days) tolerant mice. The rate of decay of PCP in serum and brain or morphine pellet-implanted animals was not different; however, in the 24 h 'pellet-removed' group, the rate of decay of PCP was increased. The results indicate that there is a two-way cross-tolerance development between PCP and morphine. The phenomenon appears to involve both dispositional and functional adaptation mechanisms.

Animals↗
PubMed1984

A striatal serotonergic involvement in the behavioural effects of anticholinesterase organophosphates.

Acute administration of the anticholinesterase agents diisopropylfluorophosphate, soman, sarin and tabun to rats in sub-convulsive doses produced tremors and hind-limb abduction. The ratios of the levels of 5-HIAA to 5-HT in the striatum showed a consistent tendency to be increased, suggesting an increase in 5-HT turnover. Both the behavioural and the biochemical changes were antagonized by atropine. The possible involvement of a cholinergic-serotonergic interaction in these tremors and hind-limb abduction is discussed.

Animals↗