Biomedical subjects

A Roy

Publications and source records attributed to A Roy.

At least 127 records · Page 7Linked to original sources

PubMed2000

Effect of tunicamycin on expression of epitopes on Japanese encephalitis virus glycoprotein E in porcine kidney cells.

The effect of tunicamycin (Tm), a glycosylation inhibitor, on the epitopes expressed on Japanese encephalitis virus (JEV) glycoprotein E (gpE) in porcine kidney stable (PS) cells was studied. At Tm concentration of 2 micrograms/ml, the virus-infected cells showed markedly reduced or no reactivity with any of the monoclonal antibodies (MAbs) directed against JEV gpE except NHs-2 and also with polyclonal antibodies (PAbs) directed against JEV. With the increase in Tm concentration to 3 micrograms/ml, a complete loss of the conventionally detected reactivity of the MAbs except NHs-2 was recorded, while the Pabs showed no decrease in their reactivity. However, the MAb NHs-2 and PAbs lost their reactivity when the cells treated with 3 micrograms/ml Tm were stained for epitopes expressed on their surface indicating that glycosylation plays a role in this phenomenon. Tissue culture fluid (TCF) displayed a low virus content in the presence of 3 micrograms/ml Tm, indicating probably a down-regulation of virus maturation inside the cells. Since preM and NS-1 proteins possess besides gpE conserved N-glycosylation sites and play a role in the maturation of JEV, their expression in nascent, i.e. non-glycosylated form might be responsible for the observed low virus content of TCF. Thus, the glycosylation of JEV gpE seems essential for the acquisition of native conformation of its epitopes and their expression in cells.

Animals↗

PubMed1999

Determination of the thermodynamic contribution to peak asymmetry of basic solutes in reversed-phase liquid chromatography.

To this day packing materials manufacturers are still trying to develop reversed-phase stationary phases that have silica more completely reacted with bonding ligands to afford more homogeneous particle surfaces. Incomplete bonding causes inhomogeneous effects that are readily observed when separating basic solutes because of the acidic silanols that are unreacted. However, it is still not understood exactly what types of silanol sites are unreacted or if metal impurities are contributing to the resulting peak asymmetry observed. A method is presented which utilizes (1) the frontal analysis method of chromatography to obtain adsorption/partition isotherms, (2) a heterogeneous Langmuir distribution model for the resulting isotherm, (3) an expectation-maximization numerical procedure to solve the mathematical problem to yield the most probable distribution of adsorption parameters, and (4) the equilibrium-dispersive model of chromatography incorporating the fitted isotherm model to check the validity of the sorption model with experimental observations. Correlation of packing materials characterization parameters with results obtained by this procedure will indicate what type of silanols or other sites are responsible for observed tailing behavior. Developers and manufacturers will then be able to more efficiently target their synthetic designs for "base-deactivated" reversed-phase silicas.

Adsorption↗

PubMed1999

Chemosensory response to high pCO is blocked by cadmium, a voltage-sensitive calcium channel blocker.

In the dark, during normocapnic (pCO2=35 Torr, pHo=7.4) normoxia (pO2=100 Torr), high pCO (>300 Torr) causes Ca2+-dependent photolabile excitation of chemosensors in the carotid body (CB). We previously proposed that the source of this Ca2+ was the [Ca2+]i stores because CO would react only intracellularly. However, influx of extracellular Ca2+ was not excluded. Now, using perfused rat CB (n=6) in the presence of normal extracellular [Ca2+] we show that chemosensory response to CO (pCO approximately 550 Torr) in normoxic (pO2 approximately 100 Torr) normocapnia (pCO2 approximately 30 Torr, pH approximately 7.4) is completely but reversibly inhibited by Cd2+ (200 microM), a voltage-gated Ca2+ channel blocker. Thus, extracellular Ca2+ is necessary for excitatory chemosensory response to high pCO. Cd2+ block occurs in spite of an enhanced [Ca2+]i rise. This shows that Ca2+ rise alone is unable to release neurotransmitter and to elicit a chemosensory response. Therefore, as a corollary, we conclude that Cd2+ blocks the Ca2+ flux that is needed for vesicle-membrane fusion for neurotransmitter release and neural discharge.

Animals↗

PubMed1999

Peak cyclosporine levels (Cmax) correlate with freedom from liver graft rejection: results of a prospective, randomized comparison of neoral and sandimmune for liver transplantation (NOF-8).

BACKGROUND: Despite two decades of use, there are limited data on the best way to administer and monitor cyclosporine (CsA) for liver transplantation. The present study was undertaken (1) to determine whether treatment with a new formulation of CsA, Neoral, would improve the results of liver transplantation; and (2) to study the relationships between pharmacokinetic parameters and clinical outcomes after transplantation. METHODS: A double-blind, randomized, comparison of Sandimmune (SIM) with Neoral (NEO) was conducted at five Canadian centers in 188 consecutive adults undergoing primary orthotopic liver transplantation. Patients were induced with intravenous CsA then switched to NEO or SIM. Dose adjustments were made daily, or as needed, to reach a target trough CsA level of 350 ng/ml in both groups. Pharmacokinetic studies were performed on days 5, 10, 15, and 16 weeks after transplantation. RESULTS: The NEO group was slightly younger, with a median age of 50 years (range: 23-70) versus 55 years (range: 24-71) for SIM (P = 0.007); otherwise the two groups were well balanced. The NEO group stopped intravenous CsA earlier (5.8+/-2.6 days vs. 8.7+/-4.7 days, P<0.0001). This group required a lower median daily oral dose (7.5 mg/kg vs. 9.0 mg/kg, P<0.01) to maintain comparable trough CsA levels. Five SIM patients, but no NEO patients, discontinued the study due to the inability to reach target trough levels of CsA within the prescribed time (P<0.05). At 4 months, there were no differences between the two groups with respect to patient survival (93% NEO vs. 91% SIM), graft survival (90% NEO vs. 86% SIM), and rejection-free survival (54.1% NEO, 51.8% SIM). The incidence of serious adverse events was also similar and did not correlate with CsA pharmacokinetic profiles. The NEO group had a higher area under the drug concentration curve for the first 6 hr after the dosing interval (AUC0-6) and peak CsA levels (Cmax). There was a strong correlation between freedom from graft rejection during the first month after transplantation and (a) AUC0-6 and (b) Cmax at days 5 and 10 after transplantation, but only in the NEO group did this reach statistical significance. In contrast, there was a poor correlation between trough CsA and graft rejection. In patients on NEO, the concentration of CsA 2 hr after dosing (C2) closely reflected AUC0-6 (r2 = 0.93), whereas there was a poorer correlation in patients on SIM (r2 = 0.73) CONCLUSIONS: Cmax and/or AUC0-6 may provide better markers than trough levels for monitoring CsA-based immune suppression after orthotopic liver transplantation. Prospective studies are underway to determine whether dosing to C2, which provides a good estimation of Cmax, can be used to take full advantage of NEO's improved absorption profile.

Adult↗

PubMed1999

Cholinergic and serotonergic alterations in the rat hippocampus following trimethyltin exposure and fetal neural transplantation.

Trimethyltin (TMT) apart from causing cholinergic denervation of the hippocampus, damages the serotonergic inputs into the hippocampus as well. In the present study, fetal cholinergic and serotonergic rich neuronal populations from septal and raphe regions, respectively, were transplanted alone or in combination (as co-grafts) in the hippocampus of TMT exposed rats. Neurotransmitter receptor binding and neurotransmitter levels were assayed 6 months post-transplantation. Fetal septal transplants (rich in cholinergic neurons) significantly restored the deficits in cholinergic (muscarinic) receptor binding and acetylcholinesterase activity caused by TMT exposure. Raphe transplants (rich in serotonergic neurons) restored the deficit in serotonergic receptor binding and serotonin levels caused by TMT. Co-grafts of fetal raphe and septal neurons restored both the cholinergic (muscarinic) and serotonergic receptor functions. The results suggest that co-grafting technique could provide a better restoration of functional deficits when more than one type of neuronal population is damaged.

Acetylcholine↗

PubMed1999

Childhood trauma and depression in alcoholics: relationship to hostility.

OBJECTIVE: To examine for a relationship between childhood trauma and depression in alcoholics. METHODS: Euthymic depressed alcoholics (N = 23) were compared with never depressed alcoholics (N = 20) for their scores on the Childhood Trauma Questionnaire (CTQ). Subjects also completed the Hostility and Direction of Hostility Questionnaire (HDHQ). RESULTS: Euthymic depressed alcoholics had significantly higher scores on the CTQ for childhood emotional abuse, physical abuse, sexual abuse, and emotional neglect. They also had significantly higher hostility scores on the HDHQ. There were significant correlations between adult hostility scores and CTQ scores for childhood emotional neglect, physical neglect, sexual abuse and total childhood trauma. CONCLUSION: A history of childhood trauma was correlated with adult depression in male alcoholics: a hostile personality dimension might be a mediating variable. LIMITATION: Subjects were queried on their memories of childhood traumas. Prospective studies are needed.

Adult↗

PubMed1999

Protein synthesis in the plastid of Plasmodium falciparum.

The plastid organelle of malarial and other apicomplexan parasites contains ribosome-like particles as well as a genome dedicated largely to specifying components of a protein expression system. We have identified plastid ribosomes using hybridization studies and show that in erythrocytic stages of Plasmodium falciparum a subset of polysomes carries plastid-specified rRNAs and mRNA, supporting the idea that protein synthesis is active in the plastid.

Animals↗

PubMed1999

Chemoenzymatic synthesis of homochiral (R)- and (S)-karahanaenol from (R)-limonene.

Terpinolene oxide, a monoterpene belonging to the p-menthane group, is easily derived from naturally abundant (R)-limonene. It was isomerized with montmorillonite clay catalyst to karahanaenone (2,2, 5-trimethylcyclohept-4-en-1-one) by ring enlargement. The enantiomers of the corresponding alcohol, karahanaenol (2,2, 5-trimethylcyclohept-4-en-1- ol), known for their individual organoleptic properties, were resolved through Pseudomonas cepacia lipase mediated enantiospecific alcoholysis of its acetate derivative.

Alcohols↗

PubMed1999

Vitamin E-TPGS increases absorption flux of an HIV protease inhibitor by enhancing its solubility and permeability.

PURPOSE: To investigate the effect of vitamin E-TPGS, d-alpha-tocopheryl polyethylene glycol 1000 succinate, on the solubility and permeability of amprenavir, a potent HIV protease inhibitor. METHODS: The aqueous solubility of amprenavir was measured as a function of vitamin E-TPGS concentration. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of vitamin E-TPGS and P-glycoprotein inhibitors. Absorption flux was estimated from Caco-2 cell permeability and aqueous solubility. RESULTS: The solubility of amprenavir in a pH 7 buffer at 37 degrees C was 0.036+/-0.007 mg/mL. The solubility linearly increased with increasing vitamin E-TPGS concentration (above 0.2 mg/mL). Polarized transport was demonstrated in the basolateral to apical direction, exceeding apical to basolateral transport by a factor of 6. The active efflux system was inhibited by vitamin E-TPGS and known P-glycoprotein inhibitors verapamil and GF120918. CONCLUSIONS: The solubility of amprenavir was improved in the presence of vitamin E-TPGS through micelle solubilization. Vitamin E-TPGS inhibits the efflux system and enhances the permeability of amprenavir. Overall, vitamin E-TPGS enhanced the absorption flux of amprenavir by increasing its solubility and permeability. The enhancement is essential to the development of the novel soft gelatin capsule formulation of amprenavir for use in the clinic.

Algorithms↗

PubMed1999

Laser light scattering immunoassay for malaria.

Laser light scattering immunoassay (LIA) was proposed as a prospective diagnostic method for the detection of antibody (or antigen) by monitoring the agglutination of antigen (or antibody) coated carrier particles using dynamic light scattering (DLS) as probe. LIA is a very sensitive assay as it can detect microscopic immune complexes even when antibody (or antigen) level is low. A sizeable number of human sera collected from malaria endemic areas and hospitals have been analysed by ELISA using Pf parasite lysate or a RESA derived synthetic peptide as antigen parallel to LIA using Pf antigen coated polystyrene latex beads. Comparative analysis of data suggests LIA to be as good as ELISA and possibly better in terms of sensitivity and simplicity. LIA can be a simple and inexpensive immunoassay suitable for field use and mass application.

Antigens, Protozoan↗

PubMed1999

Neuropsychological deficits in withdrawn cocaine-dependent males.

Previous research suggests that cocaine abuse may result in neuropsychological deficits. To examine this further, we compared cocaine-withdrawn patients (N = 35) to normal controls (N = 17) on tasks of attention, concentration, perceptual-motor speed, and cognitive flexibility. The withdrawn cocaine patients performed significantly worse on Arithmetic, Grooved Peg Board Dominant and Non-Dominant, and Trails B tests. These findings suggest that withdrawn cocaine-dependent patients have more neuropsychological impairment than normal controls.

Adult↗

PubMed1999

Effect of vitamin D3 on carcinogen-modified liver enzymes and tumour incidence in experimental rat mammary carcinogenesis.

The anticarcinogenic effect of vitamin D3 in relation to biochemical and morphological markers in 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary carcinogenesis was investigated in two different sets of experiments. For each set, female Sprague-Dawley rats were divided into four groups, to allow comparison among treated and non-treated groups. At 50 days of age, animals of group B and C were given DMBA injection (0.5 mg/100 g body weight) through the tail vein, and normal control (group A) animals received the oil emulsion vehicle alone. Vitamin D3 at the dose of 0.3 microgram/0.1 ml propylene glycol was given orally twice a week, in carcinogen as well as non-carcinogen treated animals (group C and c), until the termination of the experiments (22-24 weeks for biochemical markers, and 35 weeks for morphology). At approximately 22-24 weeks, when marked lobular hyperplasia in DMBA control groups were confirmed through histology, the biochemical markers were modulated towards normal value for vitamin D3 in the treatment group, in comparison to the disturbed values caused by carcinogen administration in group B animals. Again, vitamin D3 supplementation was effective in reducing the tumour incidence (70% in comparison to 90% in group B). The results thus clearly concluded the antineoplastic potential of vitamin D3, and the existing correlation between biological and biochemical markers.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Symmetries and induced effects in bilayer and multilayer antiferroelectric and ferrielectric liquid crystal phases.

The stable antiferroelectric and ferrielectric smectic phases which may arise below a chiral SmA* phase are investigated theoretically. The symmetry and physical properties of the bilayer and multilayer configurations are worked out. Antiferroelectric and ferrielectric bilayer and multilayer configurations, possessing an induced spontaneous ferroelectric polarization component perpendicular to the smectic layers, are shown to take place, as the result of a nonlinear piezoelectric effect. These states of low polar symmetries occur when the angle between the inlayer projections of the dipoles and the director of the molecules is different from 90 degrees.

Journal Article↗

PubMed1999

Suicidal behavior in depression: relationship to platelet serotonin transporter.

OBJECTIVE: Suicidal behavior in depressed patients is associated with low central serotonin. Thus, platelet serotonin uptake in relation to suicidal behavior in depression was examined. METHODS: Depressed patients who had never attempted suicide (n = 23) were compared with depressed patients who had never attempted suicide (n = 26) and normal controls (n = 71) for platelet serotonin uptake. RESULTS: Depressed patients who had a lifetime history of a suicide attempt had a significantly greater apparent Michaelis constant (Km) of platelet serotonin uptake than either depressed patients who had never attempted suicide or controls. Patients rated high for current suicidal ideation at the index admission had significantly higher Km values than patients rated low. Also, patients who reattempted or committed suicide during a 5-year follow-up period had significantly higher Km values than controls. Among women patients who had attempted suicide there was a significant correlation between extrapunitive hostility scores and Km values. CONCLUSION: The serotonin transporter warrants further study in relation to suicidal behavior in depression.

Adult↗

PubMed1999

Genetics of suicide in depression.

Evidence is mounting that genetic factors may be included in the many determinants of suicide. Clinical studies of psychiatric patients have suggested that risk of suicidal behavior is increased by the presence of family history of suicidality, a claim that is also supported by findings of twin and adoption studies. In addition, molecular genetic studies have reported polymorphisms in the tryptophan hydroxylase gene that is involved in the synthesis of serotonin. The genetic susceptibility to suicide, however, tends to affect individuals only in association with stress or psychiatric illness.

Adoption↗

PubMed1999

Changes in rat testicular antioxidant defence profile as a function of age and its impairment by hexachlorocyclohexane during critical stages of maturation.

Age-related changes in rat testicular oxidative stress parameters were investigated. A biphasic pattern was evident for lipid peroxidation and for the activity ratio of superoxide dismutase to catalase and glutathione peroxidase with increasing age. In the first phase of life (birth-7 days), a linear fall in lipid peroxidation was accompanied by a gradual increase in the enzyme ratio which was reversed in the second phase (15-600 days). Glutathione and ascorbic acid levels increased from birth to the 45th day and remained unchanged up till 365 days and then reduced at 600 days of age. The maximum level of H2O2 observed at birth gradually decreased till 90 days and remained unchanged up till 365 days of age; thereafter its level was elevated on day 600. The results suggest that an antioxidant defence system plays a crucial role in development and maturation of the rat testis. When the rats were treated with hexachlorocyclohexane during critical stages of testicular development (6th-30th day) and responses were evaluated on the 46th day of age, elevations in the levels of testicular lipid peroxidation and H2O2 along with reduction in levels of superoxide dismutase, catalase and ascorbic acid were observed. However, no change in glutathione and its metabolizing enzymes was recorded. On the other hand, hexachlorocyclohexane elevated total testicular Ca(2+)-Mg(2+)-ATPase activity. The results advocate for impairment of testicular functions in adult age as a consequence of some permanent lesions induced by hexachlorocyclohexane during critical stages of sexual maturation.

Aging↗

PubMed1999

Depressed patients who suicide at their first attempt have had few admissions.

A prior suicide attempt is generally considered to be an indicator of increased future suicide risk. However, approximately 50% of psychiatric patients who commit suicide have made no previous suicide attempt. Thus, an effort was made to detect other predictors of future suicide risk in this group. The records of 100 psychiatric patient suicides were examined. Patients who completed suicide at their first attempt (n = 57) were compared with patients who suicided after a previous attempt (n = 43). There were no significant differences between the two groups on any of the sociodemographic or clinical variables examined. However, patients with a primary psychiatric diagnosis of an effective disorder who committed suicide at their first attempt had had significantly less admissions than depressed patients who committed suicide after a previous attempt. The clinical implication is that the absence of many prior admissions in a depressed patient is not an indicator of low suicide risk.

Depressive Disorder↗

PubMed1999

A double-peak phenomenon in the pharmacokinetics of alprazolam after oral administration.

The pharmacokinetics of alprazolam (ALP) after i.v. and p.o. administration in rats were characterized. ALP decayed biexponentially after the i.v. dose (1.25 mg/kg), but the concentration-time profiles after the p.o. doses (7 and 12.5 mg/kg) exhibited a double-peak phenomenon. The presence of two peaks was confirmed by statistical analysis of the serum concentration data of ALP, as well as by observed double peaks in the serum concentration-time profiles of the two active metabolites (alpha-hydroxyalprazolam and 4-hydroxyalprazolam). An absorption model incorporating a delay site is proposed to describe the data, and the absolute oral bioavailability is estimated to be about 30%. The two peaks were approximately 80 to 115 min apart, and there was a delay in the absorption of close to 80% of oral ALP, regardless of dose. We hypothesize that the mechanism underlying the double-peak phenomenon is due to reduction in gastric motility caused by the muscle relaxant effect of ALP. This hypothesis is supported by the observed longer delay in the appearance of the second peak at the higher p.o. dose. Enterohepatic recycling is precluded from being the underlying mechanism, because of the presence of double peaks after the p.o. doses but not after the i.v. dose. This is the first reported case of double peaks for oral ALP, and this phenomenon has not been reported for other benzodiazepines. The double-peak phenomenon caused by the hypothesized mechanism may have important therapeutic and drug interaction implications, especially because benzodiazepines are commonly coadministered with other drugs.

Administration, Oral↗