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Biomedical subjects

M Hariharan

Publications and source records attributed to M Hariharan.

At least 37 records · Page 2Linked to original sources
PubMed1993

Assay of human plasma cortisone by liquid chromatography: normal plasma concentrations (between 8 and 10 a.m.) of cortisone and corticosterone.

A high-performance liquid chromatographic method using ultraviolet detection to quantitate human plasma concentrations of cortisone simultaneously with cortisol and corticosterone is described. The method is based on the use of an octadecyl silica column (100 mm x 2 mm I.D., 3 microns), an ultraviolet absorbance detector (242 nm) with a 10 mm path length flow-cell, and a mobile phase composed of water-tetrahydrofuran-acetonitrile (82:10:8, v/v) containing 5 ml/l triethylamine and citric acid to adjust the pH of the buffer to 6.5. Flumethasone is used as the internal standard. The detection limit of the method for the three steroids is 300 ng/l using a 1-ml sample. The average inter-assay coefficient of variation for cortisone is 3.3% and the average recovery is 100.8%. Possible interferences from common drugs and endogenous and exogenous steroids in the method have been studied. Plasma concentrations (drawn from 8 to 10 a.m.) of cortisone and corticosterone for 43 normal volunteers have been determined.

Chromatography, High Pressure Liquid↗
PubMed1993

Phenelzine produces subsensitivity to nicotine.

1. The authors attempted to detect a possible effect of treatment with phenelzine on a physiological response to nicotine in the rat. 2. Positive findings in an animal model suggest the feasibility of more complicated experiments in animals and the possibility of studies involving human subjects. 3. Treatment of Sprague Dawley rats (n = 10) with phenelzine sulfate (15.0 mg/kg ip) every 48 hours for 14 days was associated with a 73.3% decrease in the hypothermic response to nicotine. 4. Treatment with phenelzine did not enhance the rate of elimination of nicotine. 5. The authors discuss a possible relationship between changes in nicotinic mechanisms and the therapeutic actions of drugs used to treat affective illness.

Animals↗
PubMed1993

Differences between smokers and never-smokers in sensitivity to nicotine: a preliminary report.

Sensitivity to nicotine was explored using test doses administered via intra-nasal aerosol in 10 smokers and 10 never-smokers. Smokers received 1.50 mg nicotine (in 2 sprays, < 5 seconds apart, one spray per nostril); never-smokers received either 0.50 mg (n = 3) or 0.25 mg (n = 7) nicotine. Accumulation of nicotine in plasma, per unit dose administered, was nearly four times greater in never-smokers than in smokers, indicating differences in pharmacokinetic tolerance. To examine sensitivity to nicotine without this confound, peak physiological reactivity (heart rate and blood pressure changes) was divided by peak plasma nicotine increment and the ratio was expressed as a function of cotinine level prior to dosing, thereby relating sensitivity to nicotine to history of exposure. In smokers, functional sensitivity to nicotine was inversely related to customary nicotine intake, replicating previous findings for light and heavy smokers. The observation that never-smokers were not much more sensitive to nicotine than light smokers is notable given the disparity in previous history of exposure.

Administration, Intranasal↗
PubMed1993

Acute effects of alcohol administration on regional cerebral blood flow: the role of acetate.

The effect of alcohol intoxication on regional cerebral blood flow (rCBF) is unclear. The few published studies provide a mixed picture of alcohol effects, suggesting that blood flow increases at low doses and decreases at higher doses of alcohol. Using the cerebral blood flow agent 99mtechnetium hexamethyl-propylene-amine-oxime (HMPAO) and image reconstruction with single photon emission computed tomography (SPECT), we evaluated the effect of an oral dose of ethanol (0.6 g/kg) on rCBF in two age-stratified groups of healthy, nonalcoholic men (12 age 22-37 and 12 age 63-77). Intoxication was associated with a significant 4% increase in global cortical CBF (t = 2.54, p = 0.02). Changes in HMPAO uptake were negatively correlated to ethanol levels in the entire group (r = -0.47, p = 0.04). This relationship was seen in the older subgroup (r = -0.70, p = 0.05), but not in the younger group (r = -0.34, p = 0.26). In contrast, the younger group showed a significant positive correlation between rCBF and increases in acetate levels (r = 0.71, p < 0.01), which was not seen in the older group (r = -0.02, p = 0.96). These findings suggest that both acetate and alcohol contribute to the changes in CBF seen in the intoxication syndrome and that their relative influence is age-dependent.

Acetates↗
PubMed1992

Controlled dosing of nicotine via an Intranasal Nicotine Aerosol Delivery Device (INADD).

The present report describes an Intranasal Nicotine Aerosol Delivery Device (INADD) employing an artist's airbrush as aerosolizer and precise, electromechanical control of spray duration. It was designed for the administration of controlled doses of nicotine in a laboratory setting and has been used successfully in over 30 smokers and nonsmokers of both genders. In the present study, nicotine was administered to 12 male smokers at three different doses (0.05 mg, 1.00 mg, and 2.00 mg), and at the same dose (1 mg) on three different occasions. The low dose produced a minimal change in plasma nicotine, while the high dose produced a peak increment of around 16 ng/ml. The medium dose reliably produced a peak increment of around 8-9 ng/ml on all three occasions. Nicotine in plasma showed a sharp rise followed by a slower decline, mimicking the pattern associated with cigarette smoking. Physiological and biochemical responses showed significant dose-response relationships. Subjective reports suggested that aerosol dosing was somewhat aversive, but it is unclear whether this effect is intrinsic to the method or due to other factors. The device described in this report answers the need for a safe and easy means of controlling nicotine dose. Moreover, since nicotine administration via aerosol is novel for both smokers and non-smokers, minimizing the contributions of behavioral tolerance and habituation to the dosing vehicle, it lends itself to the comparison of the pharmacological effects of nicotine between experienced and naive subjects.

Administration, Intranasal↗
PubMed1992

Simultaneous assay of corticosterone and cortisol in plasma by reversed-phase liquid chromatography.

We have developed a simple, specific, and sensitive reversed-phase liquid-chromatographic method for accurate and simultaneous analysis of corticosterone and cortisol in human plasma. We achieved a detection limit of 300 ng/L for both steroids by modifying the old solid-phase extraction method to make use of "Tef Elutor" C18 columns, using a minibore (100 x 2 mm) analytical column, and using an ultraviolet detector with a 10-mm-pathlength flow cell. With the new extraction method absolute extraction efficiencies were greater than 90% for all the analytes, including the internal standard, flumethasone. The mobile phase was water (containing 5 mL of triethylamine per liter and citric acid to adjust the pH to 6.5), tetrahydrofuran, and acetonitrile (82/10/8 by vol). The average interassay CV for corticosterone at 0-25 micrograms/L was 6.5%; that for cortisol at 0-300 micrograms/L was 3.8%. The analytical recovery relative to the internal standard was 100.2% for cortisol and 102.6% for corticosterone. Possible interferences from drugs and other steroids were studied.

Chromatography, High Pressure Liquid↗
PubMed1992

A longitudinal evaluation of dexamethasone pharmacokinetics in depressed patients and normal controls.

Ten depressed patients and eight control subjects received 1 mg of dexamethasone intravenously at two different time points. Depressed patients were studied when they were depressed and following an improvement in their depression. In control subjects the first and second studies were performed approximately 1 month apart. Dexamethasone and cortisol were determined at 0, 5, 15, and 30 minutes, then at 1, 1.2, 2, 3, 4, 5, 6, 7, 9, 12, 17, and 24 hours following dexamethasone administration. Data from each patient was fit using a computer to a two compartment pharmacokinetic model and area under the time versus plasma concentration curve, elimination half-life, and clearance were also determined. Depressed patients exhibited a slower dexamethasone clearance and a larger area under the curve than control subjects at the first time point, but not at the second time point. The groups did not differ significantly in any of the other pharmacokinetic parameters (including distribution half-life, elimination half-life, or volume of distribution) at either time point. The possible causes and implications of these findings are discussed.

Adult↗
PubMed1991

A simple, sensitive liquid chromatographic assay of cis-thiothixene in plasma with coulometric detection.

A novel, simple, and very sensitive liquid-chromatographic assay with a coulometric detector has been developed for quantitating cis-thiothixene (CTX) in human plasma. A reverse phase, 5-microns cyano column (25 x 0.46 cm), a mobile phase of phosphate buffer (pH 2.5) and acetonitrile (40/60 by vol), and a coulometric detector are used for the separation of CTX, and the internal standard, trifluoperazine. CTX and trifluoperazine are extracted from alkalinized plasma into n-pentane-isopropanol (95/5 by vol) and purified by back extraction into perchloric acid. The optimum oxidation potential for the analytes is +0.8 V versus an Ag/AgCl electrode. The detection limit for CTX is 200 pg using 1 mL of plasma and CTX concentrations are linear from 0 to 40 micrograms/L. The average interassay CV is 9%, and the mean recovery is 99% relative to the internal standard. Possible interferences from various psychiatric and common drugs in the assay have been studied. The assay method was validated by determining the concentration of CTX in the plasma of 100 schizophrenic patients.

Antipsychotic Agents↗
PubMed1991

Liquid-chromatographic determination of nicotine and cotinine in urine from passive smokers: comparison with gas chromatography with a nitrogen-specific detector.

We describe a simple, sensitive, and specific high-performance liquid-chromatographic method with ultraviolet detection (256 nm) for the simultaneous analysis of nicotine and cotinine in urine of passive smokers. The analytes are extracted and purified from the complex and impure matrix in two stages; first, by liquid-liquid extraction and followed by solid-phase extraction (C2 column). We used a "DB" C8 5-microns-particle column (25 x 0.46 cm) and a mobile phase of phosphate-citrate buffer and acetonitrile (91:9 by vol) containing 5 mL of triethylamine and 600 mg of heptanesulfonate per liter, adjusted to pH 4.4, to separate the compounds. Two internal standards (2-phenylimidazole and N-ethylnorcotinine) were used. The detection limit of the HPLC assay was less than 1 microgram/L for both analytes. The average interassay CV for nicotine was 7.6%, for cotinine 6.5%, in the concentration range 0-60 micrograms/L. The mean analytical recovery of nicotine with respect to the internal standard N-ethylnorcotinine was 102% and that for cotinine was 99%; the mean absolute recoveries of the compounds were as follows: nicotine 85%, cotinine 87%, and N-ethylnorcotinine 87%. To compare the HPLC assay results of 20 samples with the more-sensitive in-laboratory gas-chromatographic method with a nitrogen-phosphorus detector, we used both N-ethylnornicotine and N-ethylnorcotinine as internal standards. The mean correlation coefficient for nicotine values between the two methods was 0.934; for cotinine, 0.987.

Child↗
PubMed1990

Alpha 2-adrenoreceptor status in obsessive-compulsive disorder.

Ten patients with obsessive-compulsive disorder (OCD) and 13 normal control subjects received intravenous infusions of 2 X 10(-6) g/kg of clonidine and normal saline on separate days. Responses to the drug relating to plasma growth hormone (GH), 3-methoxy-4-hydroxyphenylglycol (MHPG), heart rate, blood pressure, and several symptoms were determined. Additionally, platelet alpha 2-adrenoreceptor binding was measured in most of the subjects. GH, MHPG, blood pressure, and heart rate responses to clonidine did not differ between groups. As expected, patients reported more symptoms than normal subjects, and clonidine was sedating for both groups. Patients did not differ from normal subjects in the symptom response to clonidine. The maximum number of binding sites (Bmax) for tritiated clonidine was significantly greater in OCD patients than in normals. This pattern of alpha 2-adrenoreceptor status is different than the patterns in major depression and panic anxiety.

Adult↗
PubMed1990

Yohimbine bioavailability in humans.

Pharmacokinetic profiles were determined in seven healthy young male subjects following single oral and intravenous doses of 10 mg of yohimbine hydrochloride. The drug was rapidly eliminated (t1/2 beta 0.58 h orally and t1/2 beta 0.68 h intravenously). Following intravenous administration the data fit a two-compartment pharmacokinetic model, with a very rapid distribution phase (t1/2a was approximately 6 min). Both the oral and the intravenous yohimbine clearance values were high but oral clearance values were much higher (mean 9.77 ml.min-1.kg-1 intravenous versus 55.9 ml.min-1.kg-1 oral). The oral bioavailability showed great variability, ranging from 7% to 87% (mean value was 33%). The incomplete oral bioavailability of yohimbine may reflect either incomplete absorption from the gastrointestinal tract or an hepatic first pass effect. Although yohimbine is rapidly absorbed when given orally, the bioavailability is quite variable and considerable individualization of dosing may be necessary when the drug is used orally for clinical indications.

Administration, Oral↗
PubMed1990

Caffeine and human cerebral blood flow: a positron emission tomography study.

Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased paCO2 and increased systolic blood pressure significantly; the change in paCO2 did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety were also observed.

Administration, Oral↗
PubMed1990

A longitudinal evaluation of dexamethasone and cortisol plasma concentrations in the dexamethasone suppression test before and during treatment with antidepressant drugs.

Thirty depressed in- and outpatients received serial dexamethasone suppression tests (DSTs). Plasma dexamethasone and cortisol concentrations were drawn at 1600 on the day following a 1-mg oral dose of dexamethasone. The first DST was performed after patients were drug-free for a period of 1 week; the second, third, and fourth DSTs while patients received antidepressant medication. Dexamethasone and cortisol concentrations drawn in the drug-free period correlated significantly. The cortisol to dexamethasone ratio changed significantly with time in DST nonsuppressors, suggesting that nonsuppression is associated with an altered pharmacodynamic response of the hypothalamopituitary-adrenal axis to dexamethasone during depression. When dexamethasone concentrations from the drug-free period were compared with those drawn during antidepressant treatment, no significant differences were noted.

Adult↗
PubMed1989

An improved sensitive assay for simultaneous determination of plasma haloperidol and reduced haloperidol levels by liquid chromatography using a coulometric detector.

A simple, highly sensitive and specific high-performance liquid chromatographic method that uses a coulometric detector for the simultaneous assay of haloperidol and reduced haloperidol in human plasma has been developed, using bromoperidol as the internal standard. A reversed phase C8 5-microns column (25 x 0.46 cm) and a mobile phase of phosphate buffer (pH 7.0), acetonitrile, and methanol (40:20:40 vol/vol) are used for separating the analytes. The analytes are extracted from alkalinized plasma using a mixture of pentane and isopropanol (95:5 vol/vol) and purified by back extraction into a perchloric acid solution. Teflon tubes with screw caps are used throughout the extraction work. The compounds are oxidized at a potential of +0.90 V against a Ag/AgCl reference electrode. The detection limit of the assay is 50 ng/L using 1 mL of plasma. The average interassay coefficient of variation for samples of concentration 1-40 micrograms/L is approximately 8%. Possible drug interferences in the assay have been studied. The absolute recovery of the method is approximately 80%. The assay has been validated by quantitating 150 schizophrenic patients' samples.

Chromatography, High Pressure Liquid↗
PubMed1989

Free 3-methoxy-4-hydroxyphenylglycol determined in plasma by liquid chromatography with coulometric detection.

We describe a simple "high-performance" liquid-chromatographic method for determining free 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma, with coulometric detection and with 4-methoxy-3-hydroxyphenylglycol (iso-MHPG) as the internal standard. MHPG and iso-MHPG are extracted from plasma into ethyl acetate and the extract is washed with a sodium bicarbonate solution, evaporated, reconstituted, and injected into a 25 x 0.4 cm column packed with 3-micron particles of C18 material. We used a mobile phase of acetate buffer (100 mmol/L, pH 5.0) and methanol (92:8 by vol) and an oxidation voltage of 0.5 V. The detection limit of the assay is 0.1 micrograms/L. The interassay CV for a sample with a mean MHPG concentration of 3.84 micrograms/L was 5.2%. The average absolute recovery for the method was 37%.

Adult↗