No evidence for association of the T102C polymorphism in the serotonin type 2A receptor with suicidal behavior in schizophrenia.
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Alleles↗
Biomedical subjects
C H Tan
Publications and source records attributed to C H Tan.
Increased 21-hydroxylase and shutdown of C(17,20) lyase activities in testicular tissues of the grouper (Epinephelus coioides) during 17alpha-methyltestosterone-induced sex inversion.
The metabolism in vitro of [(3)H]17-hydroxyprogesterone by gonadal tissues of the grouper (Epinephelus coioides) during 17alpha-methyltestosterone (MT)-induced female-to-male sex inversion was examined. In the female phase, C(17,20) lyase, 5beta-reductase, 3alpha/beta-HSD, 20beta-HSD, and 17beta-HSD activities resulted in the biosynthesis of 5beta-pregnans and 5beta-androstanes (including 5beta-androstane-3alpha/beta, 17beta-diol, 3alpha/beta, 17alpha-dihydroxy-5beta-pregnen-20-one, and 5beta-androstane-3,17-dione). In the MT-induced male phase, however, the abrogation of C(17,20) lyase activity and the concomitant activation of 21alpha-hydroxylase/11beta-hydroxylase resulted in the preferential synthesis of polar 21alpha-hydroxlyated 5beta-pregnans (5beta-pregnan-3beta,17alpha,20beta,21alpha-tetrol and 3beta,20beta,21alpha-trihydroxy-5beta-pregnan-3-one) and corticosteroids (11-deoxycortisol and cortisol). Interestingly, synthesis of these 21alpha-hydroxylated 5beta-pregnans and corticosteroids was uniquely compartmentalized in only testicular tissues of the MT-induced males. This study shows that there is selective activation of specific steroidogenic enzymes in the different sexual phases leading to the synthesis of metabolites that may be involved in regulating sex inversion of the grouper.
17-alpha-Hydroxyprogesterone↗
The influence of induction technique on intubating conditions 1 min after rocuronium administration: a comparison of a propofol-ephedrine combination and propofol.
We conducted a double blind, prospective, controlled trial comparing intubating conditions after induction with a propofol-ephedrine combination or propofol alone, followed by rocuronium. One hundred adult patients were randomly assigned to receive either propofol 2.5 mg x kg(-1) and ephedrine 15 mg in combination or propofol 2.5 mg x kg(-1) given over 30 s, followed by rocuronium 0.6 mg x kg(-1) given over 5 s. Tracheal intubation was performed 1 min later. Jaw relaxation, vocal cord position and diaphragmatic response were used to assess intubation conditions. Tracheal intubation was successful and acceptable in all patients. There was a significantly higher proportion of intubating conditions graded as 'excellent' in the propofol-ephedrine group (84%) than in the propofol group (32%) (p < 0.0001). Vocal cord position and response to intubation were significantly better in the propofol-ephedrine group, although jaw relaxation was similar. Mean arterial pressure was maintained at pre-induction levels in the propofol-ephedrine group. In conclusion, induction with propofol and ephedrine in combination provided significantly better intubating conditions than propofol alone, when followed by rocuronium.
Adult↗
The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.
In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.
Animals↗
Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor.
BACKGROUND: Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics. METHODS: Ninety-seven healthy control subjects with no history of mental illness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were genotyped by PCR-RFLP. RESULTS: Comparison between cases and control subjects revealed no significant association between the C allele and schizophrenia. There was significant difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02-2.33) between patients who developed tardive dyskinesia and those who did not. Significant difference remains even after adjusting for age and neuroleptic dosage (p = .041) with the odds ratio at 1.64 (95% CI = 1.02-2.62). CONCLUSIONS: A genetic variant of the 5-HT2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated.
Antipsychotic Agents↗
Toward the creation of NMR databases in chiral solvents for assignments of relative and absolute stereochemistry: proof of concept.
[structure: see text] An NMR database approach in a chiral solvent allows us to predict both relative and absolute stereochemistry of an unknown compound without degradation and/or derivatization. N,alpha-Dimethylbenzylamine (DMBA) is a suitable solvent for this purpose. Using the C.5-C.10 portion of oasomycin A, the feasibility and reliability of this approach is demonstrated.
Anti-Bacterial Agents↗
The synthesis of (+)-allopumiliotoxin 323B'.
This paper describes the synthesis of (+)-allopumiliotoxin 323B' (1) using the intramolecular [3 + 2]-cycloaddition reaction of the (Z)-N-alkenylnitrone 4. This synthesis began with (R)-tert-butyl-3-hydroxy-pent-4-enoate [(R)-13] which was obtained by enzymatic resolution with Amano PS lipase. A series of manipulations gave intermediate 17 and in situ coupling with 4-benzoyloxybutanal lead to the (Z)-N-alkenylnitrone 4 which underwent an intramolecular [3 + 2]-cycloaddition reaction to give the isoxazolidine 3 as the major cycloadduct. Isoxazolidine 3 provided the piperidinone 24 which upon diastereofacial selective addition of MeMgBr gave the required tertiary alcohol 25. Formation of the indolizidine core 2 was achieved by an intramolecular S(N)2 reaction. The side chain was assembled from a Wittig reaction between the phosphorane 8 and the enantiomerically pure aldehyde 9. Further modifications afforded the aldehyde 7 which underwent an aldol condensation with the potassium enolate of the indolizidone core 2. Dehydration gave the enone 37 which was converted into the anti-diol 38 by intramolecular hydride reduction. Finally, deprotection of the BOM protecting group gave (+)-allopumiliotoxin 323B' (1).
Alkaloids↗
Toward creation of a universal NMR database for stereochemical assignment: complete structure of the desertomycin/oasomycin class of natural products.
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Anti-Bacterial Agents↗
Acoustical diffraction tomography in a finite form and its computer simulations.
Until now, all acoustical diffraction reconstruction algorithms are in infinite forms. All of these algorithms have disadvantages: severe limitations on scatterers or tedious calculations. In this paper, we present a new reconstruction algorithm in a finite form using the method of formal parameter, which is very simple. This new algorithm gives an exact reconstruction when the amplitude of the scattered wave is smaller than that of the incident wave everywhere. This assumption is much less restrictive than that for the first- and second-order Born approximations. Although this new algorithm is in a finite form, it is still an approximate one when the amplitude of the scattered wave is not smaller than that of the incident wave everywhere. However, it still gives a good reconstruction when the amplitude of the scattered wave is a little greater than that of the incident wave in some area. Some numerical examples have confirmed these conclusions.
Journal Article↗
Ruptured abdominal aortic aneurysms: a personal experience.
Despite advances in surgical technique and peri-operative care, mortality from ruptured abdominal aortic aneurysm presenting to a hospital remains around 50%. This is in contrast to the mortality rate of < 5% for elective repair. In a two and a half year period,the principal surgeon operated on 10 patients with ruptured AAA, with a peri-operative and overall mortality of 30%. One of the ten patients had a ruptured mycotic aneurysm. We present our experience with these patients and also correlate this with recent publications.
Abdominal Pain↗
Problem-based learning in medical education: the Singapore hybrid.
INTRODUCTION: Problem-based learning (PBL) is an innovative educational strategy to enhance student-centred, interactive and integrated learning through intensive small group tutorials. PBL is problem-first learning in which a commonly encountered medical problem serves as the primary focus of and stimulus for learning. Several adaptations have evolved since its implementation at McMaster University in 1969. In 1999, the Singapore medical school implemented PBL as a key feature within its new hybrid curriculum. METHODS: The review will focus on the educational implications and impact of the present curriculum reform with emphasis on the implementation of PBL within the new hybrid medical curriculum. RESULTS: Our early experience in implementing PBL resembles those of several other "traditional" medical schools, namely, a generally favourable and positive response from staff and students mixed with varying degree of anxiety to change. CONCLUSION: Appropriate training and changing the mindsets of staff and students, strong leadership from the Dean and a deep commitment by all concerned are essential to ensure the successful implementation of PBL within a "traditional" medical school. PBL will enhance the quality of medical education and the educational preparation of our students to meet the challenges of future medical practice.
Education, Medical↗
Laparoscopic fenestration of a simple hepatic cyst.
Hepatic cysts are usually asymptomatic, most being detected incidentally during imaging. Distinction has to be made between a simple hepatic cyst from more sinister types such as a parasitic cyst and a cyst occurring as part of a neoplastic process. Intervention in a simple hepatic cyst is only indicated when they become symptomatic or when they grow at a rapid rate. Surgery is the mainstay of treatment, with laparoscopic intervention becoming more and more widely accepted. We present here the first case of laparoscopic fenestration of liver cyst performed in our hospital and also review the literature on this modality of treatment.
Cysts↗
Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia.
Abnormalities of serotonin synthesis and metabolism may be associated with suicidality. The serotonin transporter gene (5-HTT) is one of the important genes involved in the regulation of serotonin neurotransmission. We examined the association of suicidal behavior in Chinese schizophrenic patients with a functional polymorphism of the promoter region of the 5-HTT gene (5-HTTLPR). The 5-HTTLPR genotype was determined by polymerase chain reaction for 76 suicidal and 262 non-suicidal patients with a diagnosis of schizophrenia (DSM-IV criteria). All subjects were unrelated to each other, and all were Chinese. There was no significant genotypic or allelic association of the 5-HTTLPR polymorphism with history of attempted suicide. From our results, this 5-HTTLPR polymorphism is unlikely to have a major effect on suicidal behavior in Chinese patients with schizophrenia.
Adult↗
Tardive dyskinesia is not associated with the serotonin gene polymorphism (5-HTTLPR) in Chinese.
Neuroleptics are the mainstay of treatment for schizophrenia, but one of the complications is the development of tardive dyskinesia (TD). The pathophysiology of TD may involve dopamine-serotonin interaction. The serotonin transporter participates in the reuptake and termination of serotonin neurotransmission, and the gene that codes for this protein is thus a candidate gene for the development of TD. There is a functional polymorphism in the transcriptional control region of the serotonin transporter gene, and we investigated the association between this polymorphism and TD in Chinese schizophrenic patients. The patients who did not differ in age and sex distribution did not show variation on the rates of TD and Abnormal Involuntary Movements Scale (AIMS) scores with genotypes. Our findings suggest that 5-HTTLPR polymorphism is not a risk factor for TD in Chinese. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:712-715, 2000.
Adult↗
Corticosteroid biosynthesis in vitro by testes of the grouper (Epinephelus coioides) after 17alpha-methyltestosterone-induced sex inversion.
This study reports the unique compartmentalization of cortisol and 11-deoxycortisol biosynthesis in vitro from [(3)H]17alpha-hydroxyprogesterone (17P) in testicular tissues of groupers after sex inversion induced by 17alpha-methyltestosterone (MT). Before MT implantation, the ovarian tissues produced only nonpolar metabolites. Following sex inversion some 6 months later, synthesis of these nonpolar metabolites was not detectable. Instead, cortisol and 11-deoxycortisol, with yields of about 3% and 14%, respectively, were synthesized together with two other polar metabolites. The corticosteroids and polar metabolites were distinctly nondetectable in ovarian tissues of the control fish throughout the experiment. While the significance of this testicular synthesis of corticosteroids is presently unclear, it could be related to the increased energy demands arising from the reorganization of gonadal tissues during sex inversion.
Animals↗
Adenosine modulates cell growth in baby hamster kidney (BHK) cells.
Adenosine is known to modulate cell growth in a variety of mammalian cells either via the activation of receptors or through metabolism. We investigated the effect of adenosine on Baby Hamster Kidney (BHK) cell growth and attempted to determine its mechanism of modulation. In wild-type BHK cells, adenosine evoked a biphasic response in which a low concentration of adenosine (1-5 microM) produced an inhibition of colony formation but at higher concentrations (up to 50 microM) this inhibition was progressively reversed. However, no biphasic response was observed in an "adenosine kinase" deficient BHK mutant, "5a", which suggests that adenosine kinase plays an important role in the modulation of growth response to adenosine. Adenosine receptors did not appear to have a role in regulating cell growth of BHK cells. Specific A1 and A2 receptor antagonists were unable to reverse the effect of adenosine on cell growth. Even though a specific A3 adenosine receptor antagonist MRS-1220 partly reversed the inhibition in colony formation at 1 microM adenosine, it also affected the transport of adenosine. Thus adenosine transport and metabolism appears to play the major role in this modulation of cell growth as 5'-amino-5'-deoxyadenosine, an adenosine kinase inhibitor, reversed the inhibition of cell growth observed at 1 microM adenosine. These results, taken together, would suggest that adenosine modulates cell growth in BHK mainly through its transport and metabolism to adenine nucleotides.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
High-dose chemotherapy and autologous stem cell rescue for acute myeloid leukemia remains a safe, effective, and valid option.
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Adolescent↗
Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats.
The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.
Animals↗