Diurnal rhythm of 3-methoxy-4-hydroxyphenylglycol (MHPG): relationship between plasma and urinary levels

Plasma and urinary levels of MHPG were determined in six normal volunteers. Samples were obtained at 3-hour intervals for plasma and at 12-hour intervals for urine. Acrophase, amplitude and period were determined for plasma MHPG levels. A sinusoidal pattern was obtained for diurnal plasma MHPG with a peak at 15:00 hrs. +/- 46 min. Urinary MHPG, corrected for creatinine levels, correlated with both 9 AM plasma MHPG and with baseline plasma MHPG. Furthermore, the relationship between plasma and urinary MHPG was linear when the rhythm of urinary levels was assumed to lag 6.2 hours behind the plasma rhythm. It was concluded that free MHPG is evenly distributed in the total body space and that conjugated MHPG is largely restricted to the blood.     

Plasma free MHPG and neuroendocrine responses to challenge doses of clonidine in Tourette's Syndrome: Preliminary report

The metabolic response to clonidine was examined in a pilot study of several patients with Tourette's Syndrome (TS). Preliminary results in a small number of patients suggested hypotheses for further investigation. Plasma free MHPG was reduced in three clinically responsive patients following a challenge dose of clonidine or haloperidol. During maintenance treatment with clonidine, a challenge dose of clonidine continued to elicit a decrease in plasma free MHPG, and CSF free MHPG was reduced. On the other hand, a clinically non-responsive TS patient on maintenance clonidine failed to show this decrease in plasma free MHPG. Prolactin, TSH, cortisol, T₃, and thyroxine indices were not changed by clonidine administration to TS patients. There was a variable GH response to clonidine. Neuroendocrine responses of patients to single oral doses of clonidine may provide a useful method of differentiating subgroups of childhood neuropsychiatric patients.     

Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol.

The effects of some antidepressants on brain total 3-methoxy-4-hydroxyphenylglycol (MHPG) were studied in the rat. Desipramine decreased and mianserine increased the brain total MHPG concentration while the other antidepressants had no effect. They were also the only antidepressants that attenuated the lowering action of clonidine on brain total MHPG, but possibly through different mechanisms. Two tertiary amine tricyclic antidepressants, amitriptyline and imipramine, appeared to enhance the lowering action of clonidine on brain total MHPG. The results suggest that antidepressants are heterogeneous in their action on brain noradrenergic mechanisms in the rat.     

Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers.

The usefulness of the plasma concentrations of two major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), as indicators of neuronal NE release was investigated. The potent alpha 2-adrenoceptor agonist, dexmedetomidine, induced only about 15% maximal reductions in the metabolite concentrations, in spite of almost total inhibition of neuronal NE release, as evidenced by 90% reductions in plasma NE concentrations. Similarly, administration of the alpha 2-adrenoceptor antagonist atipamezole was followed by only small increases in plasma DHPG and no change in MHPG levels, in spite of almost six-fold, albeit short-lasting, increases in plasma NE. In contrast, a single dose of the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide reduced plasma DHPG levels by 78% and MHPG levels by 51%. It is concluded that the plasma concentrations of DHPG and MHPG are largely determined by intraneuronal, MAO-A-dependent metabolism of NE, and do not accurately reflect acute alterations in neuronal NE release. The concentration of NE in venous plasma is clearly a more sensitive indicator of alpha 2-adrenoceptor-mediated regulation of NE release.     

Simultaneous determination of free 3-methoxy-4-hydroxymandelic acid and free 3-methoxy-4-hydroxyphenylethyleneglycol in plasma by liquid chromatography with electrochemical detection

A new assay method is described for the simultaneous determination of free 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylethyleneglycol in plasma utilizing separation and purification by Bio-Gel P-10 followed by high-performance liquid chromatography with electrochemical detection. This technique is sensitive and reliable, and offers an inexpensive and practical alternative to gas chromatographic—mass fragmentographic methods for the monitoring of plasma levels of these catecholamine metabolites in the study of selective metabolic pathways of endogenous norepinephrine originating in the peripheral and the central nervous systems.     

Characteristics of enzymes forming 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) in brain

The subcellular localization and character of the enzymes forming 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) were determined in rat brain. The aldehyde derivative of normetanephrine was produced in situ by monoamine oxidase, and two forms of aldehyde reductase were shown to metabolize the aldehyde to MOPEG. One form of the enzyme was found to have a low affinity for NADH and a higher affinity for NADPH as a cofactor, and was shown to be inhibited by pentobarbital and by high concentrations of 5-hydroxyindoleacetic acid. This enzyme form was localized primarily in the cytosol. The second aldehyde reductase had a high affinity for both NADH and NADPH, and was not inhibited to a great extent by either pentobarbital or 5-hydroxyindoleacetic acid. This second enzyme form was localized primarily in the mitochondrial fraction. The relative contribution of the two enzyme forms to MOPEG formation in homogenates was estimated, using the various inhibitors and cofactors.     

Effects of oral casokefamide on plasma levels, tolerance, and intestinal transit in man

Food-derived opioid peptides such as beta-casomorphins are of interest for treatment of chronic diarrhea. The beta-casomorphin analog casokefamide was administered orally at doses of 5.5, 8.0, and 16.0 mg to 10 healthy male volunteers, respectively. Dose-dependent increases of plasma levels with a maximum of 350 fmol/l were determined. No side-effects due to casokefamide has been observed. In comparison to placebo, casokefamide showed a trend toward prolongation of oro-caecal transit time. Orally applied casokefamide is well tolerated and may represent a useful tool for treatment of diarrhea in the future.     

A non-enzymic procedure for the quantitative analysis of (3-methoxy-4-sulphoxyphenyl)ethylene glycol (MHPG sulphate) in human urine using stable isotope dilution and gas chromatography—mass spectrometry

A method is described for the quantitative analysis of (3-methoxy-4-sulphoxyphenyl)-ethylene glycol (MHPG sulphate) in human urine, based on selected ion monitoring gas chromatography—mass spectrometry and using a specifically deuterium-labelled analogue of MHPG sulphate as internal standard. The procedure involves extraction of the urine sample on Amberlite XAD-2, followed by isolation of MHPG sulphate by column chromatography on Sephadex LH-20. Cleavage of the sulphate conjugate and formation of the MHPG tris(trifluoroscetate) derivative are carried out in a one-step reaction, without recourse to enzymic hydrolysis.     

Preliminary report on two new plasma protein polymorphisms in the goose (Anser anser)

Two-dimensional agarose gel (pH 8.6)-horizontal polyacrylamide gel (pH 9.0) electrophoresis of plasma proteins in the goose was done. This method resulted in improved separation of proteins in the pre-transferrin and transferrin regions. Preliminary evidence was presented for the existence of two new plasma protein polymorphisms.     

Preliminary report on two new plasma protein polymorphisms in the goose (Anser anser)

Two-dimensional agarose gel (pH 8.6)-horizontal poly acrylamide gel (pH 9.0) electrophoresis of plasma proteins in the goose was done. This method resulted in improved separation of proteins in the pre-transferrin and transferrin regions. Preliminary evidence was presented for the existence of two new plasma protein poly morphisrns.     

Effects of dopaminergic agonists on plasma luteinizing hormone-releasing hormone (LRH) and gonadotropins in man

To try to determine the site and mode of action of dopamine (DA) on the secretion of gonadotropins in humans, 4 series of studies were performed in 19 healthy volunteers (7 healthy males, 5 females in follicular phase and 7 postmenopausal females). The intravenous infusion of DA at the rate of 4 micrograms/kg/min decreased plasma LH levels to 75.9 +/- 3.7 (mean +/- SE)% of the initial levels. The oral administration of 500 mg of levodopa (Dopa) also suppressed the concentration of plasma LH to 73.0 +/- 3.5%, but the pretreatment with two doses of 100 mg each of carbidopa (CD), a peripheral dopa decarboxylase inhibitor, attenuated this suppressing effect of Dopa on LH levels (nadir 82.4 +/- 4.1). Plasma FSH were not significantly altered by these drugs. On the other hand, the concentration of endogenous LRH in peripheral blood remained unchanged throughout the studies. The administration of CD alone had no effect on any of these 3 parameters. These results would suggest the direct suppressing effect of DA on pituitary gonadotrophs, although the modulation at the level of the hypothalamus also cannot be ruled out.     

Effects of long-term administration of clonidine on plasma renin activity.

Plasma renin activity (PRA) was studied before and during long-term treatment with moderate oral doses (0.2 or 0.3 mg/d) of clonidine. Nine outpatients with essential hypertension received clonidine for 12 weeks; a significant decrease in blood pressure was evident in all patients. Except for a nonsignificant increase after 12 weeks of treatment, PRA values were not notably changed by clonidine therapy. No correlation was found between individual blood pressure changes and PRA variation during the study. The absence of a net effect on PRA in this study does not exclude more complex interactions of clonidine with the renin-angiotensin system. Nonetheless, clonidine cannot generally be classified as a "renin-inhibiting" drug.     

Sporotrichosis in an HIV-positive man with oral lesions: a case report

BACKGROUND: Sporotrichosis is a granulomatous fungal infection caused by Sporothrix schenckii, which frequently causes cutaneous or lymphocutaneous lesions and rarely has oral manifestations. CASE: A 38-year-old, white, HIV-positive man complained of a 5.0-cm, symptomatic, ulcerated lesion with thin, superficial granulation in the soft palate extending to the uvula. Exfoliative cytology of this oral lesion showed chronic granulomatous inflammatory alterations and extracellular fungal structures consisting of periodic acid-Schiff-positive budding cells and spherical or elongated (cigar bodies) free spore forms. CONCLUSION: The clinical and cytologic findings allowed the diagnosis of sporotrichosis, demonstrating the importance of cytodiagnosis in fungal diseases.     

Effects of methylprednisolone on exercise-induced increases of plasma levels of polymorphonuclear elastase and myeloperoxidase in man. Preliminary results

The aim of the present study was to verify whether a single oral dose of methylprednisolone could modulate the exercise-induced release of polymorphonuclear neutrophil (PMN) elastase and myeloperoxidase. Four healthy, male subjects were submitted to a 20 min downhill run (-20%) at 60% VO(2) max, 3 h after oral absorption of a placebo or a single dose of 32 mg methylprednisolone. A marked neutrophilia (+103% of basal PMN count; p < 0.02) was observed 3 h after methylprednisolone ingestion. During both exercise trials, placebo and methylprednisolone, PMN counts were increased by 46% and 19% (p < 0.05), respectively. The running test caused marked and significant (p < 0.05) increases in plasma myeloperoxidase concentration (MPO). The magnitude of MPO changes was the same in the two trials (+110%). Exercise also resulted in significant changes in plasma elastase concentration (EL) in both experimental conditions (placebo: +104%, p < 0.05; methylprednisolone: +338%, p < 0.005). Plasma elastase levels reached at the end of exercise on methylprednisolone were significantly higher than after placebo (p < 0.05). A significant relationship was found between EL and PMN in methylprednisolone trial only (r = 0.72; l0 < 0.005). These results showed that the transient exercise-induced release of elastase and myeloperoxidase were not decreased by methylprednisolone.     

The effect of oral inorganic sulphate on the metabolism of 4-hydroxyphenethylamine (tyramine) in man: tyramine O-sulphate measurement in human urine (Short Communication)

1. Urinary excretion of tyramine O-sulphate in six normal human subjects after an oral dose of 125mg of tyramine hydrochloride alone, and with a supplement of Na(2)SO(4), was determined by using chromatographic and electrophoretic separations followed by spectrophotofluorimetry. 2. In every case the excretion of tyramine O-sulphate was increased significantly after sulphate supplementation.