Biomedical subjects

D K Lim

Publications and source records attributed to D K Lim.

At least 19 recordsLinked to original sources

PubMed2003

Ketamine associated psychedelic effects and dependence.

Ketamine, a dissociative anaesthetic in use since 1970, produces prominent psychoactive effects in humans. Its non-medical use has raised concerns in many countries, including Singapore. This paper narrates the psychedelic and psychotic effects of ketamine in two ketamine dependent patients who have presented to the psychiatric service. These effects were dose-related and comprised multimodal hallucinatory experiences, a sense of slowing, paranoid ideation and enhancement of sexual, musical and sensory enjoyment. In both ketamine users the psychotic symptoms resolved quickly with symptom-targeted treatment. However, breaking the ongoing addiction cycle seemed more difficult. The neuro-pharmacological mechanisms of these phenomena are largely due to its complex multi-receptors actions, notably through the excitatory amino acids through mainly the N-methy-D-aspartate (NMDA) receptors. The detection of ketamine abuse requires a high index of suspicion and needs to be considered when there is an acute presentation with multi-modal hallucinations and psychosis.

Adult↗

PubMed2002

Risperidone and megacolon.

Risperidone is an atypical anti-psychotic medication with both 5HT2 receptor and D2 dopamine receptor antagonism. Its use has been reported to be generally safe with very few gastro-intestinal (GI) adverse or side effects. In this paper, we describe a case of megacolon associated with the use of risperidone. A 44-year-old man suffering from schizophrenia was treated with risperidone and developed gross abdominal distension after twenty-five days. Abdominal X-ray and colonoscopy showed megacolon. He improved following a surgical decompression and a reduction of risperidone dosage. We discuss the neuro-electro-physiological mechanisms of gastro-intestinal motility and conclude that the risperidone-associated megacolon may be dose-related and that there should be a heightened awareness of such possible GI complication when using risperidone.

Adult↗

PubMed2001

A small peptide derived from Flt-1 (VEGFR-1) functions as an angiogenic inhibitor.

Vascular endothelial growth factor (VEGF) is an angiogenic stimulator which functions through two endothelial specific tyrosine kinase receptors, Flt-1 and Flk-1. In this work, we show that an 11-amino acid peptide derived from the second immunoglobulin-like domain of Flt-1 functions as an angiogenic inhibitor in chick chorioallantoic membrane and inhibited VEGF-induced vascular permeability in Miles' assay without binding to VEGF directly. Circular dichroism and nuclear magnetic resonance analyses indicate that this peptide forms a stable extended structure in solution, presumably beta-sheet structure and is most likely existing as a dimer. Our results suggest that this small peptide functions as an angiogenic inhibitor by inhibiting VEGF function through a non-VEGF binding mechanism.

Angiogenesis Inhibitors↗

PubMed2001

Impairments of learning and memory following intracerebroventricular administration of AF64A in rats.

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform from 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th day, but not 8th day. In the active avoidance for the pre-trained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for spatial cognition.

Animals↗

PubMed2001

Changes in the glutamate release and uptake of cerebellar cells in perinatally nicotine-exposed rat pups.

Cerebellar granule and glial cells were cultured from 7 day-old rat pups after pre- and post-natal nicotine treatment. Ten days later, the basal release of glutamate in the granule cells prepared from the pre- and post-natally nicotine-exposed pups was higher and lower than the controls, respectively. The N-methyl-D-aspartate-induced release of glutamate was higher in the granule cells of post-natal nicotine exposed rats. However, the nicotine-induced glutamate release was either unchanged or was lower in the granule cells of all nicotine-treated pups. The basal glutamate uptake was higher in the glial cells from those exposed pre-natally and lower in the continuously nicotine-exposed pups. The sensitivities of L-trans-pyrrolidine-2,4-dicarboxylic acid on glutamate uptake were higher in all nicotine treated groups. There was a higher number of specific [3H]dizocilpine binding sites in the pre- or continuously nicotine-exposed group. These results suggest that the cerebellar cell properties are altered after perinatal nicotine exposure and that the development of an excitatory amino acid system might be affected differently depending on the nicotine exposure time.

Animals↗

PubMed2000

Subacute nicotine exposure in cultured cerebellar cells increased the release and uptake of glutamate.

Cerebellar granule and glial cells prepared from 7 day-old rat pups were used to investigate the effects of sub-acute nicotine exposure on the glutamatergic nervous system. These cells were exposed to nicotine in various concentrations for 2 to 10 days in situ. Nicotine-exposure did not result in any changes in cerebellar granule and glial cell viability at concentrations of up to 500 microM. In cerebellar granule cells, the basal extracellular levels of glutamate, aspartate and glycine were enhanced in the nicotine-exposed granule cells. In addition, the responses of N-methyl-D-aspartate (NMDA)-induced glutamate release were enhanced at low NMDA concentrations in the nicotine-exposed granule cells. However, this decreased at higher NMDA concentrations. The glutaminase activity was increased after nicotine exposure. In cerebellar glial cells, glutamate uptake in the nicotine-exposed glial cells were either increased at low nicotine exposure levels or decreased at higher levels. The inhibition of glutamate uptake by L-trans-pyrollidine-2,4-dicarboxylic acid (PDC) was lower in glial cells exposed to 50 microM nicotine. Glutamine synthetase activity was lower in glial cells exposed to 100 or 500 microM of nicotine. These results indicate that the properties of cerebellar granule and glial cells may alter after subacute nicotine exposure. Furthermore, they suggest that nicotine exposure during development may modulate glutamatergic nervous activity.

Animals↗

PubMed1998

Effects of chronic lead exposure on glutamate release and uptake in cerebellar cells of rat pups.

Changes in the release and uptake of glutamate in cerebellar granule and glial cells of offspring of lead-exposed mothers were determined. In cultured cerebellar granule cells exposed to lead for 5 days, glutamate release was less influenced upon N-methyl-D-aspartate (NMDA) stimulation than that in the control. Although the NMDA-stimulated release of glutamate in cerebellar granule cells prepared from lead-exposed first generation pups was not different from that of the control group, the S-nitroso-N-acetylpenicillamine (SNAP)-stimulated release of glutamate in cerebellar granule cells obtained from lead-treated pups was less elevated than that in the control. Furthermore, in cerebellar granule cells obtained from lead-exposed second generations pups, glutamate release did not respond to both NMDA and SNAP stimulation. In cerebellar glial cells exposed to lead, the basal glutamate uptake was not changed. However, the L-trans-pyrollidine-2,4-dicarboxylic acid (PDC)-blocking effects was significantly reduced. In glial cells obtained from lead-exposed pups, the glutamate uptake was also less blocked by PDC than that in the control. Further decreases in PDC-blocking effects were observed in cerebellar glial cells obtained from lead-treated second generation pups compared to those from the control group. These results indicate that lead exposure induces the changes in the sensitivities of the glutamate release and uptake transporter. In addition, these results suggest that lead exposure might affect the intracellular signalling pathway and transmission in glutamatergic nervous system.

Animals↗

PubMed1998

Excitatory amino acids and lead-induced neurotoxicity.

The NMDA receptor non-competitive antagonist, [3H]MK-801, was used as a ligand for an autoradiographic study to determine the effects of lead on NMDA receptor in rat brain. Adult male rats were given lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i.p. for 7 days. Lead levels were detected in blood (41.1 micrograms/dl) and brain (16.7-29.4 micrograms/g). Concentrations of lead in various brain regions did not differ. [3H]MK-801 binding was heterogeneous throughout the brain with the following order of binding densities: hippocampal formation > cortex > caudate-putamen > thalamus > brainstem. Lead exposure caused a decrease in [3H]MK-801 binding to NMDA receptors in the hippocampal formation including CA2 stratum radiatum, CA3 stratum radiatum and presubiculum, and in the agranular insular, cingulate, entorhinal, orbital, parietal and perirhinal areas of cerebral cortex. In another experiment, female rats were exposed pre- and post-natally from the 4th +/- 1 post conception day with 1,000 ppm lead in their drinking water. This treatment continued after weaning. No effects of lead on [3H]MK-801 binding were found at postnatal day (PM) 28. However, lead caused a significant increase in [3H]MK-801 binding in the hippocampus including CA1 and CA2, and in the occipital and temporal cortical areas at PN 56 and at PN 112. Increases in [3H]MK-801 binding were also found in entorhinal cortex and dentate gyrus at PN 112. The hippocampal formation is a critical neural structure for learning and memory processes, whereas cortical and subcortical regions are involved in the modulation of complex behavioral processes. NMDA receptors have been shown to play a key role in synaptic plasticity underlying learning and memory. Therefore, lead-induced alterations of ligand binding to NMDA receptors in the hippocampal formation and cortical areas may play a role in lead-induced neurotoxicity.

Animals↗

PubMed1998

Responses to N-methyl-D-aspartate and kainic acid in cerebellar granule cells of lead-exposed rat pups.

To determine changes in response to N-methyl-D-aspartate (NMDA) and kainic acid (KA) in cerebellar granule cells of offspring of lead-exposed mothers, pregnant rats received 0.25% lead acetate in their drinking water 2 days after mating. The control animals were given sodium acetate (0.125%) in their drinking water. The cerebellar granule cells were cultured from 8-day old pups. Changes in the levels of cytosolic Ca++ and cGMP and the release of glutamic acid were measured using fura-2 spectrofluorometer, radio-immunoassay, and HPLC, respectively. Increases in cytosolic Ca++ in response to 50 microM of NMDA and KA were less responsive (77%) in the lead exposed group as compared to that of the control group. However, the maximum responses to KA were not different. The NMDA- and KA-stimulated release of glutamate from cerebellar granule cells prepared from lead-exposed pups were also significantly reduced. While the NMDA-induced elevation of cGMP was not affected in the lead-exposed pups, the normal KA-induced increases in cGMP level in cerebellar granule cells of lead-exposed pups was not observed. The specific binding of [3H]MK-801 was significantly lower in cerebellar granule cells of the lead-exposed pups. These results indicate that lead exposure to the mother affects excitatory amino acid systems during the development of the offspring.

Administration, Oral↗

PubMed1997

Effects of subacute lead exposure on [3H]MK-801 binding in hippocampus and cerebral cortex in the adult rat.

We used the NMDA receptor non-competitive antagonist, [3H]MK-801, as a ligand for an autoradiographic study to determine the effects of lead on NMDA receptor in the rat brain. Adult male rats were administered lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i.p. for 7 days. High lead levels were detected in blood (41.1 microg/dl) and in brain (16.7-29.4 microg/g). Concentrations of lead in brain regions were not significantly different. The [3H]MK-801 binding was heterogeneously distributed throughout the rat brain with the following order of binding densities: hippocampal formation > cortex > caudate-putamen > thalamus > brainstem. Lead exposure produced a significant decrease in [3H]MK-801 binding to the NMDA receptor in the hippocampal formation including CA2 stratum radiatum, CA3 stratum radiatum, hilus dentate gyrus and presubiculum, and in the cerebral cortex including agranular insular, cingulate, entorhinal, orbital, parietal and perirhinal areas. The hippocampal formation is known as a critical neural structure for learning and memory processes, whereas, cortical and subcortical regions have been demonstrated to be involved in the modulation of complex behavioral processes. The NMDA receptor has been demonstrated to play a key role in synaptic plasticity underlying learning and memory. Lead-induced alterations of NMDA receptors in the hippocampal formation and cortical areas may play a role in lead-induced neurotoxicity.

Animals↗

PubMed1995

A novel quantitative receptor autoradiography and in situ hybridization histochemistry technique using storage phosphor screen imaging.

A new technique of image acquisition for quantitative receptor autoradiography and in situ hybridization histochemistry was developed using storage phosphor screen imaging. This method was at least 4-5 times faster than conventional film densitometry. Two of the advantages of the phosphor screen method are high sensitivity and wide linear range of response. Other aspects of this method were compared with those of conventional densitometry. Use of storage phosphor screen imaging will allow greatly increased speed of pharmacological screening procedures that utilize quantitative autoradiography.

Animals↗

PubMed1995

The first human case of Clinostomum complanatum (Trematoda: Clinostomidae) infection in Korea.

The authors present the first human case of Clinostomum pharyngitis in Taegu, Korea. The patient was a 56-year old male who visited an otolaryngology clinic due to foreign body sensation and pain of the pharyngeal region for 3-4 days. He used to eat raw fresh-water fish. Otolaryngological examinations revealed a living worm adhered to the right posterior pharyngeal wall. The worm removed was identified as C. complanatum after morphological observations. It is likely that more attention should be paid to eating raw fresh-water fish in Korea with regards to Clinostomum pharyngitis.

Animals↗

PubMed1994

Changes in the central dopaminergic systems in the streptozotocin-induced diabetic rats.

The behavioral response, dopamine metabolism, and characteristics of dopamine subtypes after developing the hyperglycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set and duration of cataleptic behavior responded to SCH 23390 injection was delayed and shortened, respectively. However, the cataleptic responses to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were significantly reduced in the striata of hyperglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased turnover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 receptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in the striata was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine metabolism.

Animals↗

PubMed1992

Effects of bicuculline on [3H]SR 95531 binding in discrete regions of rat brains.

Effects of bicuculline in vitro, and acute and chronic treatment of a subconvulsive dose of bicuculline on [3H]SR 95531 binding to discrete regions of rat brains were studied in Sprague-Dawley rats. Scatchard analysis of the binding isotherms exhibited two populations of binding sites for [3H]SR 95531 in frontal cortex, cerebellum, striatum and substantia nigra. The apparent KD for high-affinity sites was significantly increased in the frontal cortex and cerebellum in the presence of bicuculline (1 microM) with no change in Bmax. In contrast, the apparent affinity for low-affinity sites was not altered in the presence of bicuculline in these regions, whereas the Bmax was significantly decreased in the cerebellum. Following acute (2 mg/kg, i.p.) or chronic (2 mg/kg, i.p. for 10 days) bicuculline treatment, [3H]SR 95531 binding was also investigated in various regions of brains. The acute bicuculline treatment did not affect the [3H]SR 95531 binding in any of the regions studied. In contrast, apparent affinity for [3H]SR 95531 was significantly decreased in low-affinity sites of all regions studied in rats treated chronically with bicuculline. The Bmax values of high and low-affinity sites were significantly increased in the cerebellum with no change in the frontal cortex, striatum and substantia nigra. The present study demonstrates that chronic bicuculline treatment decreases apparent affinity of [3H]SR 95531 binding whereas the treatment increases apparent affinity of [3H]muscimol binding (1) in various brain regions. The results indicate that significant increase in Bmax of [3H]SR 95531 and [3H]muscimol binding in the cerebellum may be due to true up-regulation of GABA binding sites, involving increased de novo synthesis of receptor protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Trihexyphenidyl enhances physostigmine prophylaxis against soman poisoning in guinea pigs.

The protective effects of simultaneous and continuous administration of physostigmine and trihexyphenidyl against soman-induced toxicity were studied in guinea pigs. Not only did trihexyphenidyl reduce physostigmine-induced toxicity when it was administered continuously to the animals along with physostigmine, the combination afforded greater protection from soman lethality than did either agent administered alone. The combination pretreatment also gave better protection against soman-induced body weight loss and decreased water consumption and attenuated the down-regulation of cholinergic receptors which occurred when physostigmine alone was used. The onsets of other soman-induced toxicity signs were delayed significantly by the combination pretreatment regimen. These results suggest that simultaneous administration of the combination of physostigmine and trihexyphenidyl may be more useful than physostigmine alone as prophylaxis against soman poisoning.

Animals↗

PubMed1990

Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: I. Levels of dopamine and metabolites.

Effects of acute and subacute cocaine administration on dopamine (DA) and its metabolites in striata and nucleus accumbens of nine week-old Wistar-Kyoto and spontaneously hypertensive rats were studied. Levels of DA,3,4-dihydroxphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC-EC. There were no differences in DA levels in striata and nucleus accumbens between control WKY and SHR. Levels of DA in two brain regions were unaffected in groups treated acutely with cocaine. Both strains showed a significant increase in striatal HVA 2 hr after cocaine injection. Seven day treatment declined DA levels in striatum of WKY and in nucleus accumbens of SHR. However, only WKY treated subacutely with cocaine showed significantly increased HVA either with or without changes in DOPAC in nucleus accumbens and striatum, respectively. Increased DOPAC/DA and HVA/DA ratios appeared only in striatum of WKY and in nucleus accumbens of SHR following subacute treatment. These results suggest that subacute cocaine administration affects DA levels in striata and nucleus accumbens differently between WKY and SHR.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: II. Dopamine receptors.

The characteristics of D-1 and D-2 dopamine receptors after acute and subacute cocaine administration were determined in striata and nuclei accumbens from WKY and SHR. In striata from acutely treated rats, significant increases in D-2 receptor density were observed at 30 min, 2 or 24 h following cocaine injection in both strains without changes in affinities. The density of D-1 receptors was significantly decreased 30 min after the injection in WKY, but not in SHR. In striata from subacutely treated rats, the density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinities of both binding sites remained unchanged. In nuclei accumbens, the change in both D-1 and D-2 receptors after cocaine administration were similar to those observed in the striatum. The results suggest that cocaine administration alters dopamine receptor binding characteristics. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

Animals↗

PubMed1990

Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: III. Dopamine uptake.

The characteristics of dopamine uptake after acute and subacute cocaine administration were determined in striata from WKY and SHR. In acutely-treated (40 mg/kg, s.c.) rats, significant increases in the Vmax of dopamine uptake were observed 30 min after the cocaine injection in both strains, without changes in Km values. The in vitro IC50 for cocaine was significantly decreased at 30 min in WKY and at 2 h in SHR. However, the in vitro IC50 for GBR-12909 was significantly increased at 30 min and at 2 h in both strains following cocaine administration. In both strains, the density (Bmax) of the [3H]GBR-12935 binding site was significantly increased at 30 min and at 2 h with no changes in Kd. In subacutely-treated (20 mg/kg, twice daily for 3 or 7 days) rats, a significant increase in the Km for dopamine uptake was observed in 7 day treated SHR. The in vitro IC50 for GBR-12909 was significantly increased in 3 day treated WKY. The results suggest that cocaine administration alters dopamine uptake and characteristics of dopamine uptake sites in the rat brain.

Animals↗