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Biomedical subjects

A K Dhar

Publications and source records attributed to A K Dhar.

At least 37 records · Page 2Linked to original sources

Molecular cloning and sequencing of the capsid and the nuclear inclusion protein genes of a North American PVYN isolate.

The sequence of the 3'-terminal 3258 nucleotides of a tobacco veinal necrosis strain of a potato virus Y (PVYN) isolate from North America was determined. The sequence revealed an open reading frame of 2931 nucleotides, of which the start codon was not identified. The nontranslated region contains 327 nucleotides upstream of a poly(A) tract. The open reading frame encodes a large polyprotein containing 976 amino acids. The data indicate that the coat protein (CP) and the nuclear inclusion protein (NIb) are derived from the large polypeptide by proteolytic cleavage similar to many other potyviruses. The putative cleavage sites of NIa/NIb and NIb/CP correspond to Q/A and Q/G sequences, respectively, as in other PVYN isolates. The CP and NIb contain 267 and 519 amino acid residues, respectively. Higher sequence homology of CP was observed with other PVYN isolates than with the PVYO isolates.

Amino Acid Sequence↗

Verbal memory and plasma drug concentrations in elderly depressives treated with nortriptyline.

Performance on a verbal memory task and affective state were assessed in geriatric major depressives before and during 6 weeks of treatment with nortriptyline (NT) in a fixed-dose design study. Higher plasma NT concentration was associated with poorer free recall but better affective outcome. In contrast, higher plasma Z-10-hydroxynortriptyline (Z-10-OH-NT) concentration was associated with more efficient free recall. Concentration-effect relationships were noted in patients later classified as cognitively unimpaired using the Dementia Rating Scale after optimal treatment, rather than in those with residual cognitive impairment.

Aged↗

Isomers of 10-hydroxynortriptyline in geriatric depression.

In geriatric, depressed inpatients treated with nortriptyline (NT), total unconjugated plasma concentrations of the Z isomer of the 10-hydroxylated metabolite (10-OH-NT) were determined simultaneously with concentrations of the E isomer by high-performance liquid chromatography. Z-10-OH-NT concentrations averaged 14% of E-10-OH-NT concentrations.

Aged↗

Effect of supplemental carbidopa on bioavailability of L-dopa.

The effect of doubling carbidopa intake on single dose bioavailability of L-Dopa was examined in five parkinsonian patients. Increasing carbidopa from a mean of 145 to 290 mg/day caused a mean increase in peak plasma Dopa concentrations from 1,893 +/- 476 to 2,733 +/- 607 ng/ml and area under the Dopa plasma concentration versus time curve of 24.6 +/- 10.0%, as well as a decrease in the time to peak plasma concentration to 0.7 +/- 0.2 versus 1.2 +/- 0.3 h. Increasing the within-dose ratio of carbidopa to L-Dopa, even in patients receiving "maximally effective" doses of carbidopa, further increases bioavailability of L-Dopa, presumably by inhibiting "first pass' metabolism in the gut.

Aged↗

Plasma 10-hydroxynortriptyline and ECG changes in elderly depressed patients.

Among 18 elderly depressed patients given ECGs before and during nortriptyline treatment, plasma E-10-hydroxynortriptyline and the sum of E-10-hydroxynortriptyline and nortriptyline distinguished the group with conduction/repolarization effects. Plasma nortriptyline, age, drug dose, and baseline cardiovascular status did not.

Age Factors↗

Plasma 10-hydroxynortriptyline in elderly depressed patients.

Plasma concentrations of nortriptyline (NT) and of unconjugated E-10-hydroxynortriptyline (E-10-OH-NT) were measured under steady-state conditions in elderly (60 yr and older) and young adult (40 yr and younger) patients treated with NT. The two groups received equivalent doses of NT. Plasma NT concentrations of the two groups did not differ, but plasma E-10-OH-NT concentrations were higher in the elderly. The plasma E-10-OH-NT/NT ratios were twice as high in the elderly group. Plasma E-10-OH-NT/NT ratios varied 2000% between individuals in the elderly group but were stable within individuals. Plasma E-10-OH-NT/NT ratios correlated positively but weakly with serum creatinine concentrations.

Adolescent↗

Efficacy and feasibility of high dose tricyclic antidepressant treatment in elderly delusional depressives.

It is unclear why delusional depressives respond poorly to usual doses of tricyclic antidepressants alone. Seventeen elderly, delusional depressives were treated with high doses of imipramine or desmethylimipramine while monitoring plasma levels in an open study. Four of seven patients who received an adequate trial responded, but over half of the total sample had to be dropped due to intolerable side effects or worsening clinical condition. Antidepressants in high doses may be effective for part of the delusional depression sample, but this potentially effective pharmacologic therapy is not feasible in a large percentage of elderly or agitated patients.

Aged↗

Improved liquid-chromatographic determination of haloperidol in plasma.

This method for determination of haloperidol in plasma is based on "high-performance" isocratic liquid chromatography with the use of a C8 bonded reversed-phase column at room temperature. Haloperidol and the internal standard (chloro-substituted analog) are extracted from alkalinized plasma into isoamyl alcohol/heptane (1.5/98.5 by vol) and back-extracted into dilute H2SO4. The aqueous phase is directly injected onto the column. The mobile phase is a 30/45/25 (by vol) mixture of phosphate buffer (16.5 mmol/L, pH 7.0), acetonitrile, and methanol. Unlike other liquid-chromatographic procedures for haloperidol, commonly used psychotropic drugs do not interfere. Analysis can be completed within an hour. The procedure is extremely sensitive (1.0 microgram/L) and is well reproducible (CV 5.6% for a 2.5 micrograms/L concentration in plasma).

Child↗

Determination of diazepam and its pharmacologically active metabolites in blood by bond Elut column extraction and reversed-phase high-performance liquid chromatography.

A rapid and quantitative analytical micro method for the determination of diazepam and its major pharmacologically active metabolites utilizing high-performance liquid chromatography (HPLC) is reported. The drug and its metabolites were extracted from 50-100 microliter samples of whole blood, serum or plasma using Bond Elut C 18 column and quantitated by high-performance liquid chromatography, using Technician Fast-LC-C-8 (RP 5 micrometers) bonded column and a mobile phase consisting of 53% methanol, 1% acetonitrile in KH2PO4 buffer and 10 microliters/l triethylamine. Methyl nitrazepam and medazepam were used as internal and external standards respectively. The extraction and recovery of diazepam and its major pharmacologically active metabolites, i.e., 3-hydroxydiazepam, desmethyldiazepam and oxazepam from blood were higher than 88% for all compounds. The minimum detection range of each compound was approximately 2.5 ng per 100-microliter sample. This micro method of simultaneous quantitation of diazepam and its major pharmacologically active metabolites provides a valuable technique for the study of diazepam pharmacokinetics in a small animal model without disturbance of normal hemodynamics from excess blood loss, as well as in clinical evaluation of pediatric patients.

Chromatography, High Pressure Liquid↗

Improved gas chromatographic procedure for the determination of clonazepam levels in plasma using a nitrogen-sensitive detector.

A gas-liquid chromatographic procedure (GLC) is described for the determination of clonazepam in plasma. The drug is extracted from buffered plasma at pH 9.0 with diethyl ether and then back-extracted into 6 N hydrochloric acid-6N sulfuric acid (95:5) and hydrolyzed at 100 degrees C to convert the drug into its benzophenone derivative. The benzophenone derivative of flurazepam is added to plasma as an internal reference standard. Drug derivatives are finally extracted from the neutralized aqueous phase and assayed by GLC. The present procedure makes use of a nitrogen-sensitive detector which is more stable and selective than the commonly employed electron-capture procedure. The sensitivity of the detector for clonazepam is 1 ng/ml.

Anticonvulsants↗