Atrial ectopics with clozapine-risperidone combination.
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Adult↗
Biomedical subjects
C H Tan
Publications and source records attributed to C H Tan.
Serum and urine risperidone concentrations in an acute overdose.
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Adult↗
Clinical evaluation and plasma clozapine concentrations in Chinese patients with schizophrenia.
The relationships between clozapine dosages, plasma concentrations, and clinical responses in Chinese schizophrenics were studied. Fourteen treatment-refractory schizophrenic patients were treated with clozapine for 12 weeks. Patients were assessed before and after 6 and 12 weeks of treatment using the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI), and the Simpson-Angus Scale for Extrapyramidal Side Effect. Plasma clozapine concentrations were determined by high-performance liquid chromatography. Ten patients (71.4%) responded after 12 weeks of treatment. Although the mean daily dosage at week 12 (373 +/- 90 mg/day) was lower than that reported in American trials (444 mg/day), the mean plasma clozapine concentration attained (1,078 +/- 385 ng/ml) was higher. This higher concentration may be due to the lower body wight and the preponderance of women among our patients, absence of smoking and alcohol use, and/or ethnic difference between Chinese and non-Chinese. There was wide interindividual variation in the plasma clozapine concentrations. Compared with other studies, the plasma clozapine concentrations and the response rate were higher. Although the sample size was small, the findings are suggestive of pharmacokinetic and pharmacodynamic ethnic differences in Chinese with clozapine therapy.
Adult↗
Substrate specificities of alpha-galactosidases from yeasts.
Twenty-nine strains of yeasts, which are capable of using galactose, melibiose, or raffinose, were screened for alpha-galactosidase production. Among the strains, 5 produced intracellular and extracellular alpha-galactosidases, and 2 produced only intracellular enzyme. Substrate specificities of these enzymes were explored using 6(3)-alpha-D-galactosyl-1,4-beta-D-mannotriose and 6(3)-alpha-D-galactosyl-1,4-beta-D-mannotetraose. All enzymes liberated the terminal galactose from 6(3)-alpha-D-galactosyl-1,4-beta-D-mannotriose, but did not the stub galactose from 6(3)-alpha-D-galactosyl-1,4-beta-D-mannotetraose.
Fungal Proteins↗
Disordered water homeostasis in Asian patients with schizophrenia.
OBJECTIVE: The aim of this study was to determine the prevalence of polydipsia-hyponatremia among patients with schizophrenia in an Asian mental hospital. METHOD: Seven hundred and twenty-eight inpatients with schizophrenia were assessed for polydipsia-hyponatremia using case notes reviews, specific gravity of urine, normalised diurnal weight gain, and serum sodium levels. RESULTS: One hundred and three (13.8%) patients had polydipsia, 30 (4.1%) had polydipsia-hyponatremia and 14 (1.9%) had a history of water intoxication. Eight of the 30 patients were receiving carbamazepine, three were on tricyclic antidepressants and two had diabetes mellitus and were on sulfonylureas. CONCLUSION: The prevalence of water intoxication among polydipsic patients was low compared to Western studies. This could be due to different methods of assessing polyuria, or ethnic differences and/or the prohibition of smoking in our patients. Certain medications might have also contributed to hyponatremia.
Adult↗
The NUH Memory Clinic. National University Hospital, Singapore.
OBJECTIVE: To assess the cognitive performance of elderly patients referred to the memory clinic. DESIGN: The patients were interviewed using the computerised mental state programme, GMS-AGECAT, and assessed on the Cognitive Assessment Scale (CAS) which includes the Elderly Cognitive Assessment Questionnaire (ECAQ) and the Cambridge Memory Test (CMT), modified for Chinese elderly. SUBJECTS: There were 72 Chinese elderly subjects aged 65 years and above, referred to the NUH Memory Clinic in the first year. RESULTS: Only 45 (62.5%) of the 72 subjects were diagnosed to have dementia using DSM III R criteria. There were 25 cases of Alzheimer's Disease and 20 multi-infarct dementia. In the non-demented group, 15 (20.8%) had depression or anxiety disorders and 12 (16.7%), had no mental disorders but had physical illness which could affect memory. There was a highly significant difference in the ECAQ, CMT and CAS scores of demented and non-demented elderly. There was also a significant difference in the cognitive performance of elderly with mild dementia and those with no mental disorder. CONCLUSION: The memory clinic is a useful facility for the diagnosis and management of dementia. The Cognitive Assessment Scale provides a valid and reliable battery of tests for dementia.
Aged↗
Synaptosomal binding of 125I-labelled daboiatoxin, a new PLA2 neurotoxin from the venom of Daboia russelli siamensis.
Daboiatoxin (DbTx), the PLA2 neurotoxin from Daboia russelli siamensis venom, was shown to bind specifically and saturably to rat cerebrocortical synaptosomes and synaptic membrane fragments. Two families of binding sites were detected by equilibrium binding analysis in the presence and absence of Ca2+. Scatchard analysis of biphasic plateaus revealed Kdl 5 nM and Bmax1, 6 pmoles/mg protein, and Kd2 80 nM and Bmax2 20 pmoles/mg protein, respectively, for the high- and low-affinity binding sites. The binding of 125I-DbTx to synaptosomes did not show marked dependence on Ca2+, Mg2+, Co2+ and Sr2+. Native DbTx was the only strong competitor to 125I-DbTx synaptosomal binding (IC50 12.5 nM, KI 5.5 nM). Two other crotalid PLA2 neurotoxins, crotoxin CB and mojave toxin basic subunit, and nontoxic C. Atrox PLA2 enzyme, were relatively weaker inhibitors, while two viperid PLA2 neurotoxins, ammodytoxin A and VRV PL V, were very weak inhibitors. Crotoxin CA was a poor inhibitor even at microM concentrations, whereas no inhibitory effect at all was observed with crotoxin CACB, ammodytoxin C, VRV PL VIIIa, taipoxin, beta-bungarotoxin, or with PLA2 enzymes from N. naja venom, E. schistosa venom, bee venom and porcine pancreas. All other pharmacologically active ligands examined (epinephrine, norepinephrine, histamine, choline, dopamine, serotonin, GABA, naloxone, WB-4101, atropine, hexamethonium and alpha-bun-garotoxin) also failed to interfere with 125I-DbTx binding. As those competitors that showed partial inhibition were effective only at microM concentration range compared to the Kd (5 nM) of 125I-DbTx synaptosomal binding, DbTx could well recognize a different neuronal binding site. Rabbit anti-DbTx polyclonal antisera completely blocked the specific binding. When a range of Ca2+ and K+ channels modulators were examined, Ca2+ channel blockers (omega-conotoxins GVIA and MVIIC, taicatoxin, calciseptine and nitrendiprene) did not affect the binding even at high concentrations, while charybdotoxin was the only K+ channel effector that could partially displace 125I-DbTx synaptosomal binding amongst the K+ channel blockers tested (apamin, dendrotoxin-I, iberiotoxin, MCD-peptide, 4-aminopyridine and tetraethylammonium), suggesting that neither K+ nor Ca2+ channels are associated with DbTx binding sites.
Animals↗
Inhibition of sodium-dependent uptake processes in purified rat brain synaptosomes by Lophozozymus pictor toxin and palytoxin.
To get an insight into the mechanism of neurotoxicity exhibited by Lophozozymus pictor toxin (LPTX) and the toxin isolated from P.caribaeorum (C-PTX) studies were carried out on the effect of these toxins on the uptake of selected substrates (neurotransmitters, amino acids and glucose) in isolated nerve endings. The toxins were found to inhibit the uptake of gamma-aminobutyric acid (GABA), noradrenaline, choline, L-leucine and 2-deoxy-D-glucose in rat brain synaptosomes. LPTX- or C-PTX-induced inhibition of synaptosomal uptake was reduced in the absence of Na+ in the assay medium. Synaptosomes exposed to LPTX and C-PTX release K+ in a dose-dependent manner. Ouabain, a selective inhibitor of the plasma membrane Na+, K(+)-ATPase could inhibit LPTX- and C-PTX-induced K+ efflux from synaptosomes and alleviate the toxin-induced inhibition of synaptosomal GABA uptake. It appears that the induction of ionic flux is the primary cause of toxicity by these toxins leading to the inhibition of Na(+)-dependent uptake processes in synaptosomes. The antagonistic action of ouabain suggests the involvement of the membrane sodium pump in the development of cytotoxicity.
Acrylamides↗
YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity.
YY1 is a multifunctional transcription factor that has been shown to regulate the expression of a number of cellular and viral genes, including the human papillomavirus (HPV) oncogenes E6 and E7. In this study, we have analyzed the YY1-mediated repression of the HPV type 16 (HPV-16) E6-E7 promoter. A systematic analysis to identify YY1 sites present in the HPV-16 long control region showed that of 30 potential YY1 binding motifs, 24 bound purified recombinant YY1 protein, but only 10 of these were able to bind YY1 when nuclear extracts of HeLa cells were used. Of these, only a cluster of five sites, located in the vicinity of an AP-1 motif, were found to be responsible for repressing the HPV-16 P97 promoter. All five sites were required for repression, the mutation of any one site giving rise to a four- to sixfold increase in transcriptional activity. The target for YY1-mediated repression was identified as being a highly conserved AP-1 site, and we propose that AP-1 may represent a common target for YY1 repression. We also provide data demonstrating that YY1 can bind the transcriptional coactivator CREB-binding protein and propose a potentially novel mechanism by which YY1 represses AP-1 activity as a result of this YY1-CREB-binding protein interaction.
DNA-Binding Proteins↗
Hoarding and clozapine-risperidone combination.
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Adult↗
Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.
Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.
Activities of Daily Living↗
High and low affinity transport of L-arginine in rat brain synaptosomes.
The uptake of L-arginine into purified rat brain synaptosomes was investigated with respect to time and various concentrations of L-[3H]arginine. Specific uptake was found to be linear with time for up to 5 min of incubation at 37 degrees C. Electrolytes, including sodium chloride, potassium chloride, magnesium chloride and calcium chloride, inhibited uptake of 3 microM L-arginine, and the inhibitory effect increased with increased electrolyte concentration under constant osmolarity. It was found that L-arginine was transported into synaptosomes by two uptake components--a high affinity component (3.5 microM) and a low affinity component (100 microM). These two components were similar to the Ly+ system because of their extreme sensitivity to inhibition by L-lysine and L-ornithine but were distinguishable from each other by kinetic analysis of the uptake data and by their relative sensitivity to inhibition by several amino acids.
Amino Acids↗
Ethanolic extraction, purification, and partial characterization of a fluorescent toxin from the coral reef crab, Lophozozymus pictor.
A purification procedure for Lophozozymus pictor toxin (LPTX) following ethanolic extraction of whole crab homogenate is described. The ethanol-extracted toxin (LPTX-E) had higher yield and specific activity than the hot aqueous-extracted one (LPTX-H). It was found that LPTX-E was fluorescent and cochromatographed with LPTX-H on two-dimensional thin-layer chromatography. Although LPTX-E, LPTX-H, and palytoxin (P. caribaeorum, PTX) had similar migration and retention times when analysed on high performance capillary electrophoresis and gel permeation-high performance liquid chromatography respectively, LPTX-E and LPTX-H were both fluorescent in contrast to PTX. In addition, LPTX-E had a different retention time compared with PTX when chromatographed on reversed phase high performance liquid chromatography in the solvent system 80% acetonitrile and 0.02 M Tris-HCl, pH 7.2, at a 4:1 ratio, respectively, indicating some differences in their chemical structures.
Acetonitriles↗
In vitro metabolism of testosterone by gonads of the grouper (Epinephelus tauvina) before and after sex inversion with 17 alpha-methyltestosterone.
The steroidogenic potential of gonadal tissues of the protogynous grouper (Epinephelus tauvina) was examined before and after sex inversion with 17 alpha-methyltestosterone. Incubations of gonadal tissues of the fish with [3H]testosterone resulted in the biosynthesis of 5 beta-androstane-3 beta, 17 beta-diol and 5 beta-dihydrotestosterone as the only metabolites in the female phase. Although the production of these 5 beta-reduced androgens persisted in the male phase, there was a shift toward the production of 11 beta-hydroxytestosterone and 11-ketotestosterone as major metabolites.
Androstane-3,17-diol↗
Resting and thrombin-stimulated cytosolic calcium in platelets of patients with alcoholic withdrawal, bipolar manic disorder and chronic schizophrenia.
Cytosolic calcium concentration ([Ca2+]i) in platelets during resting state and when stimulated by thrombin were measured in 7 alcoholic dependent patients in the state of withdrawal (AW) who were receiving diazepam, 7 bipolar manic patients (BM) who were receiving haloperidol, 15 drug free chronic schizophrenic patients (CS) and 26 normal controls (NC). Resting [Ca2+]i in these groups were quite similar at (mean +/- SEM) 112 +/- 20 nM, 127 +/- 18 nM, 103 +/- 16 nM and 106 +/- 8 nM respectively. Increase in platelet [Ca2+]i in response to 0.1 U/ml thrombin was expressed as delta[Ca2+]i and its percentage over resting [Ca2+]i as %[Ca2+]i. Both delta[Ca2+]i and %[Ca2+]i were significantly higher (p = 0.006 and 0.0045 respectively, ANOVA, Waller-Duncan) in AW (433 +/- 71 nM, 417 +/- 58%) than the other groups: NC (223 +/- 25 nM, 225 +/- 23%), BM (309 +/- 38 nM, 260 +/- 31%), and CS (261 +/- 34 nM, 280 +/- 29%) respectively. In vitro incubation of platelets from NC with diazepam or haloperidol did not affect the resting [Ca2+]i and %[Ca2+]i. The enhanced [Ca2+]i response to thrombin in platelets of AW is unlikely to be due to diazepam. It may indicate an abnormality in platelets during the withdrawal phase. Treatment with haloperidol resulted in slightly higher [Ca2+]i in platelets of BM. Platelet [Ca2+]i in drug-free CS was not different from NC.
Adolescent↗
A major lethal factor of the venom of Burmese Russell's viper (Daboia russelli siamensis): isolation, N-terminal sequencing and biological activities of daboiatoxin.
A major lethal factor, daboiatoxin (DbTx), showing strong PLA2 activity (specific activity 91.7 nmoles/min/mg), was purified to homogeneity from the venom of Burmese Russell's viper (Daboia r. siamensis) by a combination of gel filtration on Sephadex G-75 and ion-exchange chromatography on CM-Sephadex C-25, followed by purification on high-performance gel filtration Shim-pack Diol-150 column. DbTx is a single-chain PLA2 toxin with approximate mol. wt 15,000 as determined by HPLC gel filtration and SDS-PAGE. It constitutes 12% of total venom protein and is the main lethal component of Burmese Russell's viper venom with an LD50 i.p. (0.05 mg/kg) 12-fold greater than that of the whole venom (LD50 i.p. 0.6 mg/kg). DbTx produces neurotoxic symptoms in mice and exhibits potent oedema-inducing activity (minimum oedema dose 0.05 microgram), indirect haemolytic activity and a strong myonecrotic activity, but no haemorrhagic activity. DbTx is cytotoxic to HeLa cells causing cytolysis of the cells 24 hr post-exposure to toxin (50 micrograms/ml). The first 20 N-terminal amino acid sequence (NFFQF AEMIV KMTGK EAVHS) shows a significant resemblance to those of the PLA2s from the venoms of Bulgarian viper (V. a. ammodytes) and Taiwan Russell's viper (V. r. formosensis).
Amino Acid Sequence↗
Bioactivity and mechanism of action of Lophozozymus pictor toxin.
The bioactivity of Lophozozymus pictor toxin (LPTX) and the possible mechanism of action of the purified toxin are described. LPTX is found to possess palytoxin-like bioactivities. Besides exhibiting cytotoxic and haemolytic properties, LPTX causes the release of K+ from erythrocytes and inhibits 2-[14C]deoxy-D-glucose uptake into HeLa cells. Although LPTX acts on HeLa cell and erythrocyte membranes, it does not interact with mitochondrial or liposomal membranes containing different phospholipid compositions. Ouabain, but not sphingomyelin, is able to prevent the toxic effects of LPTX. This antagonistic effect of ouabain on LPTX suggests that the toxin might mediate its toxic effects via the membrane Na+/K(+)-ATPase but not through interaction with membrane lipids.
Animals↗