Biomedical subjects

C L Wong

Publications and source records attributed to C L Wong.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of sympathomimetic agents on opiate analgesia, tolerance and dependence in mice.

The effects of chronic pretreatment with ephedrine and phenylpropanolamine (PPA) on the antinociceptive activities of morphine and codeine, as well as their effects on the induction and expression of tolerance to, and dependence on morphine and codeine in mice are reported. Chronic pretreatment with ephedrine or PPA attenuated the antinociceptive effects of subsequently administered morphine or codeine. When administered during the induction phase, sympathomimetics enhanced opiate tolerance with little or no effect on the development of physical dependence. Given in the expression phase, ephedrine and PPA did not significantly affect tolerance, whereas there was significant suppression of withdrawal signs. The possible implications of these results are discussed.

Analgesia↗

PubMed1991

Interaction between the inhibitory effects of morphine and clonidine on intestinal transit in mice.

Both clonidine and morphine dose-dependently inhibited intestinal transit in mice. This inhibitory effect of clonidine was antagonized by prior administration of yohimbine but not by naloxone, while morphine's effect was antagonized by both yohimbine and naloxone. Morphine pretreatment did not induce any apparent tolerance to the effect of clonidine and morphine tested 4 h later. However, yohimbine became more potent in antagonizing the effect of clonidine while naloxone remained ineffective. Morphine pretreatment enhanced the antagonistic effectiveness of both yohimbine and naloxone against morphine. Clonidine pretreatment at a dose that did not induce any tolerance slightly enhanced the antagonistic effects of yohimbine and naloxone against morphine. Yohimbine also became more effective against clonidine but naloxone remained ineffective. At higher doses of clonidine pretreatment tolerance to the effects of morphine and clonidine were observed. These results suggest that both alpha 2-adrenoceptors and opioid receptors are involved in the inhibitory action of morphine on intestinal transit, while clonidine mainly acts through the alpha 2-adrenoceptors. In addition, there is a close interaction between the alpha 2-adrenoceptors and opioid receptors in the intestine.

Animals↗

PubMed1991

Immunophenotypic characterisation of monocytoid differentiation markers in acute non-lymphoblastic leukaemias.

The FAB classification of acute non-lymphoblastic leukaemias has been shown to have some clinical use in the prognostication of patient survival. ANLL with monocytoid features (M4, M5) fare worse than those which are predominantly myeloblastic (M1, M2). Classification is, however, sometimes difficult if non-specific esterase activity is not strongly expressed. Monoclonal antibody characterisation of myeloid differentiation antigens may be of some use as a supplementary aid. We immunophenotyped the blast cells from 26 cases for HLA-Dr, CD14 (Mo2, My4), CD13 (My17) and CD33 (My9) expression using the APAAP method. A combination of CD14 and CD33 used together was useful in differentiating myeloblastic from monocytoid acute non-lymphoblastic leukaemias. We conclude that the use of surface markers is a useful adjunct to the diagnostic means presently available.

Antibodies, Monoclonal↗

PubMed1991

The disposition of antituberculous drugs in plasma of elderly patients. I. Isoniazid and hydrazine metabolite.

The plasma profiles of isoniazid (INH) and hydrazine (HYD) metabolite were compared in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month after treatment for tuberculosis with INH, rifampicin (RIF) and pyrazinamide (PZA). There was no difference in the pharmacokinetics of INH between the two age groups. The clearance for INH at steady-state was significantly lower than after the first dose. After the first dose the maximum concentration (Cmax) for HYD was significantly higher (p less than 0.05) in the elderly (0.4 +/- 0.07 microgram/ml) than in the young (0.24 +/- 0.08 microgram/ml). HYD is produced in significant amounts during INH metabolism and this should not be neglected when evaluating INH related toxicity.

Acetylation↗

PubMed1991

The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide.

The pharmacokinetics of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) were studied in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month of treatment for pulmonary tuberculosis. Elderly patients exhibited more side effects but there were no age-related changes in the pharmacokinetics of any of the three drugs when used in this combination. The clearance for INH and RIF at steady-state were significantly lower than after first-dose, while that of PZA remained unchanged. At steady-state the clearances for INH and RIF were not characteristic of polymorphic metabolism and auto-enzyme induction, respectively. Elderly patients are more sensitive to antituberculous (anti-TB) drugs; therefore, a modification in the dosage for this patient group should be considered.

Adult↗

PubMed1991

The pharmacokinetics of isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid of rabbits.

The pharmacokinetics of isoniazid (INH) and hydrazine metabolite (HYD) in plasma and cerebrospinal fluid (CSF) of ten rabbits was studied after separate intravenous (i.v.) and oral (p.o.) administration in a crossover study. The concentrations of INH and HYD in the biological fluids were determined by high performance liquid chromatography (HPLC). There was no difference in the area under plasma concentration-time curves, indicating that oral absorption was complete. The mean apparent volume of distribution after i.v. (3.02 +/- 0.55 L) was smaller (p less than 0.01) than that after p.o. (4.29 +/- 1.25 L) dosing. The elimination t1/2 of INH in CSF was longer (p less than 0.005) than that in plasma after either route of administration. There was no significant barrier to the penetration of INH into the CSF from the general circulation. The HYD plasma concentrations were similar after either route. HYD was eliminated at a slower rate (Ke = 0.17 h-1) than INH (Ke = 0.59 h-1). There was prolonged exposure of the body to HYD (greater than 6 h - above 0.1 micrograms/ml).

Administration, Oral↗

PubMed1990

Preliminary study on the antinociceptive effect of elephant beta-endorphin.

1. Intraventricular administration of human beta-endorphin and elephant beta-endorphin significantly prolonged the tail flick response tested 30 min later. However, elephant beta-endorphin was about 7-8 times more potent than human beta-endorphin in the tail flick test. 2. beta-Endorphin antagonized the antinociceptive effect of both human beta-endorphin and elephant beta-endorphin by the same extent. Naloxone also antagonized the antinociceptive effects of the beta-endorphins but it was less effective than beta-endorphin. 3. Human beta-endorphin and elephant beta-endorphin were of equal potency in inhibiting the abdominal constriction response induced by intraperitoneal (i.p.) acetic acid. Both beta-endorphin and naloxone antagonized these effects of the beta-endorphins with naloxone being more effective. 4. The present study showed that different opioid receptor subtypes may be involved in the tail flick test and the abdominal constriction test. Furthermore, elephant beta-endorphin was a better antinociceptive agent than human beta-endorphin in the tail flick test.

Analgesics↗

PubMed1990

The possible involvement of alpha-adrenoceptors in the intestinal effect of nalbuphine in mice.

In the present study, intestinal motility was measured by the transit of charcoal meal through the small intestine in mice. Nalbuphine, given subcutaneously, caused a dose-dependent inhibition of the intestinal transit in mice. This inhibitory effect of nalbuphine was antagonized by prior s.c. administration of naloxone and MR2266. In addition, the inhibitory effect of nalbuphine was also suppressed by prior administration of yohimbine, an alpha 2-adrenoceptor antagonist, and phentolamine, an antagonist for both alpha 1- and alpha 2-adrenoceptors. Unlike morphine, the intestinal inhibitory effect of nalbuphine was also antagonized by prazosin, a selective alpha 1-adrenoceptor antagonist. However, prior administration of propranolol did not alter this effect of nalbuphine. These adrenoceptor antagonists by themselves, at the doses used, had no effect on the rate of intestinal transit of a charcoal meal in mice. These results suggest that both alpha 1- and alpha 2-adrenoceptors may be involved in the intestinal effect of nalbuphine while beta-adrenoceptors do not appear to play any significant role in this aspect of nalbuphine's action.

Animals↗

PubMed1988

Effect of oestradiol replacement on swim-induced antinociception in ovariectomized mice.

1. A 30 s swim in water at 30 degrees C reduced the number of abdominal constrictions produced in female mice by intraperitoneally administered acetic acid and this antinociceptive effect was antagonized by naloxone. 2. Oophorectomy abolished the development of antinociceptive activity in response to swim. 3. The development of antinociceptive activity and naloxone antagonism were restored in oophorectomized mice maintained on daily oestradiol injection. 4. The present study indicates that the increase in abdominal constriction response to acetic acid in oophorectomized mice was due to the removal of the source of female sex hormone.

Acetates↗

PubMed1987

The effect of gonadectomy on antinociception induced in mice by swim stress.

A 30 s swim in water at 30 degrees C reduced the number of abdominal constrictions produced in mice by i.p. acetic acid. Naloxone antagonised this stress-induced antinociception in the female but not in the male. Orchidectomy altered neither the antinociception nor its insensitivity to naloxone antagonism. However, oophorectomy completely abolished the antinociception induced by the swim. These results suggest a sex difference in the involvement of the endogenous opioid system in swim stress-induced antinociception in mice.

Animals↗

PubMed1987

Liquid chromatographic assay for the simultaneous determination of pyrazinamide and rifampicin in serum samples from patients with tuberculous meningitis.

A simple high-performance liquid chromatographic assay for the simultaneous determination of pyrazinamide and rifampicin in serum from patients with tuberculous meningitis is presented. The drugs and internal standard, p-acetamidobenzoic acid, were extracted from the acidified sample containing 2% ascorbic acid at pH 4.2 into dichloromethane-diethyl ether (2:3). The solvent extract was evaporated to dryness with the aid of nitrogen and the residue redissolved in methanol (75 microliters). The concentrate was analysed by a liquid chromatograph using a reversed-phase 30-microns C8 pre-column linked to a 5-microns C8 analytical column with a gradient solvent programme, which delivered 6% to 48% (v/v) acetonitrile in phosphate buffer (10 mM potassium dihydrogenphosphate, pH 3.5) in 10 min at 1.5 ml/min. The eluate was detected at 215 nm. Twelve patients with tuberculous meningitis were given daily chemotherapy, and their serum samples were assayed for pyrazinamide and rifampicin.

Calibration↗

PubMed1987

The effect of nalbuphine on gastrointestinal transit in mice.

Nalbuphine given subcutaneously (s.c.) inhibited gastrointestinal transit in a dose-dependent manner. Prior s.c. administration of naloxone hydrochloride suppressed the inhibitory effect of nalbuphine on gastrointestinal transit. Naloxone methobromide (naloxone MB), a quaternary compound, was also effective in antagonising this effect of nalbuphine but was less effective than naloxone hydrochloride. Furthermore, prior s.c. administration of Mr 2266 also antagonised the gastrointestinal transit inhibitory action of nalbuphine. When given centrally, either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), naloxone hydrochloride was ineffective in antagonising s.c. nalbuphine. Similar findings were observed with centrally administered Mr 2266. In addition, i.c. nalbuphine had a minimal effect on gastrointestinal transit while i.c.v. nalbuphine only caused slight inhibition of gastrointestinal transit. It was concluded that nalbuphine inhibits gastrointestinal transit mainly through peripheral opiate receptors.

Animals↗

PubMed1987

Sex difference in naloxone antagonism of swim stress-induced antinociception in mice.

A 30 sec swim in water at 30 degrees C reduced the number of abdominal constrictions produced in mice by the intraperitoneal injection of acetic acid. In male mice this reduction in abdominal constrictions induced by swim stress was not affected by prior subcutaneous administration of naloxone hydrochloride. However, in the female mice naloxone hydrochloride administered 5 min, 10 min, or 15 min before the 30 sec swim dose-dependently antagonized the effect of swim stress on the abdominal constriction response to i.p. acetic acid. In view of the possibility that female mice may perceive the stress at different intensity from those of the male, the effects of different swimming durations on female mice were also studied. It was found that a 15 sec swim in water at 30 degrees C was sufficient to induce antinociceptive response to i.p. acetic acid. The antinociceptive effect was greater if the duration of swim was extended to 60 sec. In both instances, prior administration of naloxone dose-dependently reduced the antinociceptive effect induced by swimming. These results suggest sex difference in the involvement of endogenous opioid system in swim stress-induced antinociception in mice.

Acetates↗

PubMed1986

High-performance liquid chromatographic determination of pyrazinamide in cerebrospinal fluid and plasma in the rabbit.

A simple procedure for the determination of pyrazinamide in plasma and cerebrospinal fluid in the rabbit is described. The assay involves a preliminary extraction of the drug and an internal standard, paracetamol, from the acidified sample (pH 4.2). The extract is evaporated to dryness at 45 degrees C and the residue is redissolved in methanol (50 microliters). A 25-microliters aliquot is injected into the liquid chromatograph and eluted with acetonitrile-10 mM phosphate buffer of pH 3.5 (10:90, v/v) on a 30-microns C8 pre-column linked to a 5-microns C8 reversed-phase column at ambient temperature (25 +/- 1 degree C). The eluate is detected at 215 nm. The method has been used to investigate the disposition of pyrazinamide in plasma and cerebrospinal fluid in six rabbits.

Animals↗

PubMed1986

A study on the antagonism of the intestinal inhibitory effects of morphine and clonidine by yohimbine in mice.

In mice, clonidine administered subcutaneously caused a dose-dependent inhibition of the intestinal motility as assayed by the movement of a charcoal meal. This inhibitory effect of clonidine was antagonized dose-dependently by prior subcutaneous or intracisternal administration of yohimbine. However, yohimbine given intracerebroventricularly was ineffective in antagonising the intestinal inhibitory action of clonidine. Clonidine administered centrally, either intracisternally or intracerebroventricularly, caused a dose-dependent inhibition of intestinal motility. Clonidine given by the intracisternal route appeared to be more effective than by the intracerebroventricular route. Centrally administered clonidine was antagonized by prior subcutaneous administration of yohimbine. The antagonism was related to the doses of yohimbine given. Subcutaneously administered morphine caused a dose-dependent inhibition of intestinal motility and this effect was antagonized by prior subcutaneous administration of yohimbine. However, administration of yohimbine centrally, either intracisternally or intracerebroventricularly, did not affect the intestinal inhibitory action of morphine. On the other hand, morphine injected centrally, either intracisternally or intracerebroventricularly, dose-dependently inhibited the motility of the intestine; such inhibitory action was antagonized by prior subcutaneous administration of yohimbine. The present study suggests that clonidine inhibits intestinal motility at both central and peripheral sites through alpha 2-adrenoceptors. Morphine also inhibits intestinal motility by both central and peripheral mechanisms but it appears that yohimbine only modifies the peripheral aspect of morphine's action.

Animals↗

PubMed1986

Effects of superfusion of morphine and enkephalins on the activity of single units in the spinal trigeminal nucleus and cuneate nucleus of cat.

The effects of superfusion of morphine, met-enkephalin and D-ala2-met5-enkephalinamide on the spontaneous neural discharge rates of units in the spinal trigeminal nucleus and cuneate nucleus of decerebrate cats were studied. The drugs were superfused onto the dorsum of the exposed surface of the caudal medulla overlying these nuclei. Some of these neurons were identified by their response to innocuous mechanical stimuli delivered to the skin. In the caudal spinal trigeminal nucleus, morphine caused a dose-dependent suppression of the spontaneous discharge rate in the majority of the neurons studied. Endogenous opiate peptide, met-enkephalin or its synthetic analogue, D-ala2-met5-enkephalinamide caused an initial reduction, followed by a rebound of the discharge rate to the control value. These depressant effects of morphine and enkephalins were antagonized by concomitant superfusion of the opiate antagonist naloxone. In the main cuneate nucleus, however, similar doses of morphine, met-enkephalin and D-ala2-met5-enkephalinamide have little if any significant effect on the spontaneous activity of the neurons studied. These results provide electrophysiological evidence for the presence of opiate receptors in the caudal spinal trigeminal nucleus and the relative lack of such receptors in the main cuneate nucleus.

Action Potentials↗

PubMed1986

Central and peripheral inhibitory effects of morphine on intestinal transit in mice.

In the present study, intestinal motility was measured by the transit of charcoal meal through the small intestine in mice. Morphine, given subcutaneously, caused a dose-dependent slowing of the rate of intestinal transit. This inhibitory effect of morphine was antagonised by prior subcutaneous administration of naloxone hydrochloride or its quaternary analog naloxone methylbromide. However, on a weight basis, naloxone methylbromide was only about half as potent as naloxone hydrochloride. Morphine given centrally, either intracerebroventricularly or intracisternally, caused a dose-related inhibition of intestinal transit, the intracerebroventricular route appearing to be more effective. The effects of centrally administered morphine were antagonised by prior subcutaneous administration of naloxone hydrochloride but not by naloxone methylbromide. The narcotic antagonists administered centrally were effective in suppressing the inhibitory effect of subcutaneously administered morphine. When given intracerebroventricularly naloxone methylbromide was as effective as naloxone hydrochloride, while by intracisternal route, it was about half as potent as naloxone hydrochloride. These results provide evidence that peripherally administered morphine inhibits intestinal transit by both central and peripheral mechanisms. Of the central routes of administration studied, it appears that the sites around the lateral ventricles play a more significant role in the intestinal inhibitory actions of morphine.

Animals↗

PubMed1985

The involvement of histamine receptors in morphine-induced increased naloxone potency in mice.

In the present study, the effect of histamine agonists and antagonists on morphine antinociception and naloxone antagonism were studied. The antinociceptive effect of morphine and the antagonistic effect of naloxone were measured by the acetic acid-induced abdominal constriction test in mice. It was found that pretreatment with 2-methylhistamine, a histamine H1-receptor agonist, altered neither the antinociceptive effect of morphine nor the antagonistic effect of naloxone. When 2-methylhistamine was given together with morphine as pretreatment, the naloxone potency was enhanced compared with pretreatment by morphine alone. Pretreatment with 2-pyridylethylamine, another histamine H1-receptor agonist, alone or in combination with morphine, altered neither the antinociceptive activity of morphine nor the antagonistic potency of naloxone. Pretreatment with 4-methylhistamine, a histamine H2-receptor agonist, did not alter the antinociceptive activity of morphine or the antagonistic effect of naloxone. However, when given together with morphine as the pretreatment, the antinociceptive effect of morphine as well as the antagonistic activity of naloxone were enhanced. Similar effects were observed with dimaprit, another histamine H2-receptor agonist. Pretreatment with diphenhydramine, a histamine H1-receptor antagonist, alone or in combination with morphine, altered neither the antinociceptive effect of morphine nor the antagonistic activity of naloxone. Pretreatment with cimetidine, a histamine H2-receptor antagonist, did not affect the antinociceptive effect of morphine and the antagonistic potency of naloxone. However, when given together with morphine as pretreatment, it suppressed the ability of morphine in inducing an increase in naloxone potency. Similar effects were observed with ranitidine, another histamine H2-receptor blocker.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗