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Biomedical subjects

D D Godse

Publications and source records attributed to D D Godse.

35 records · Page 2Linked to original sources

A gas chromatographic-mass spectrometric (GC-MS) assay for 3-methoxy-4-hydroxyphenethyleneglycol and vanilmandelic acid in human serum.

Procedure for the quantification of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and vanilmandelic acid (VMA) in human serum are described. MHPG was selectively acetylated then determined as its 4-acetyl-di-trifluoroacetyl derivative and VMA as its di-pentabluoropropionyl-methyl ester. Deuterium-labeled MHPG and VMA were used as internal standards. Each of these metabolities and the resprective internal standards was recorded by double ion monitoring respectively, and the ratios were determined for specificity. Assay sensitivities of 1.0 ng/ml for MHPG and 2.0 ng/ml for VMA were achieved using 0.5 ml of serum. Total and free MHPG concentrations in human serum were determined to be 16.5 ng/ml +/- 4.4 (S.D.) and 4.6 ng/ml +/- 1.0 respectively from 10 normal male subjects. Free VMA concentrations were 7.0 ng/ml +/- 1.5; thus the ratio of MHPG/VMA was calculated to be 2.4 +/- 0.7 in these subjects. Of these two major normal metabolites of norepinephrine, MHPG is regarded to be largely derived from the central nervous system while VMA is from the periphery. The procedures are highly specific as well as simple and sensitive enough to permit simultaneous measurement of these two metabolites in a series of multiple samples from an individual.

Adult↗

CNS monoamine metabolism in bipolar affective disorder. Evaluation using a peripheral decarboxylase inhibitor.

Carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, inhibits the peripheral synthesis of nor-adrenaline, serotonin, and tryptamine. By reducing the peripheral component of end-products of these amines in urine, a more accurate assessment of central nervous system (CNS) amine metabolism is provided. Urinary 5-hydroxyindoleacetic acid (5-HIAA), tryptamine, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured over ten days in ten normal controls and eight bipolar depressives. After a three-day baseline period, carbidopa, 100 mg three times a day, was given for seven days. While the patients tended to excrete less MHPG in the baseline period, these differences became somewhat larger, and statistically significant when peripheral contributions were reduced with carbidopa. While carbidopa resulted in striking inhibition of tryptamine excretion, and smaller decreases in the excretion of 5-HIAA and MHPG, evidently from storage pools, there were no significant differences in degree of inhibition between patients and controls. Absolute values of 5-HIAA and tryptamine were similar for both groups, during the baseline and again with carbidopa. These results after carbidopa are compatible with a central catecholaminergic deficit in bipolar depressives and the use of urinary MHPG as an index of CNS catecholamine function.

Adolescent↗

The effect of a peripheral decarboxylase inhibitor (carbidopa) on monoamine and neuroendocrine function in man.

Carbidopa, a selective extracerebral decarboxylase inhibitor, was given to 10 normal volunteers to determine its effects on endogenous catecholamine, indoleamine, and endocrine function. Tryptamine, which is largely extracerebral in origin, was inhibited markedly (80 percent) by the carbidopa; 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenolglycol (MHPG) excretion also were inhibited by the drug but not to the same degree as tryptamine. These differential results may be due partly to the higher central nervous system origin of the 5-HIAA and MHPG but also to a peripheral "stores" effect. In addition, carbidopa resulted in significant increases in plasma prolactin and a small but significant decrease in plasma glucagon.

Adult↗

Urinary cyclic AMP in relation to lithium treatment in manic-depressive illness.

Urnary cyclic AMP was measured longitudinally in six patients with bipolar affective disorder. The values varied from 3.55 to 19.0 mugmol/24 hours with considerable variation between subjects. Three of these patients improved with administration of lithium carbonate. This improvement was not correlated with a change in cyclic AMP excretion. Five normal male volunteers were studied over a 5-day period. The urinary excretion for this group showed the same large intersubject variability but smaller intrasubject variation as was found for the patient group. It is suggested that erroneous results may be obtained for urinary cyclic AMP excretion if mean group values are used from patients not studied longitudinally.

Adult↗

Taming effects of handling on 6-hydroxydopamine induced ratge.

The purpose of this experiment was to determine the importance of handling to the expression of hyperemotional behaviors, i.e., rage, known to occur after chronic depletion of brain norepinephrine (NE) and dopamine (DA) following central injection of 6-hydroxydopamine (6-OHDA) in rats. Five min of handling per day for 6 consecutive days reduced resistane to capture as well as the magnitude and frequency of startle responding following one 300 mug injection of 6-OHDA intracisternally. Both 6-OHDA-handled and 6-OHDA-unhandled rats showed comparable levels of brain NE, DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), comparable resting levels of plasma corticosterone, and comparable adrenal weights. These data demonstrate the importance of handling to the expression of 6-OHDA-induced rage and emphasize the importance of controlling for handling as a variable which can significantly affect the assessment of rage by behavioral criteria in this animal model of hyperemotionality.

Anger↗

Determination of picogram levels of brain serotonin by a simplified liquid chromatographic electrochemical detection assay.

A simplified assay is described for measurement of picogram amounts of serotonin (5-HT) by high pressure liquid chromatography with electrochemical detection (LCEC). The procedure involves pre-purification of brain 5-HT by adsorption on Amberlite CG-50. Serotonin is subsequently resolved and detected by LCEC on Zipax SCX resin. The present method gives working sensitivities of at least 100 pg, tissue recoveries of 95% and very low interassay variability (coefficient of variation = 3%). Determination of rat brain area 5-HT by this LCEC method is described and compared to other high sensitivity methods.

Animals↗