Plasma DA Research Articles

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Effects of Supplemental Japanese Pepper Seed on Thermoregulation, and Blood Monoamines in Heat Exposed Broiler Chicks

Background: This study was carried out to assess the effects of enriched feed with Japanese Pepper Seeds (1 and 2%) on plasma monoamine and thermoregulation in broilers. Materials and Methods: A day old male broiler chicks were obtained from hatchery (Fukuda, Japan), and were kept in cages with floor of wire-mesh; 3 broilers in each cage. The surrounding heat was controlled at 30 ± 1 0C for three days in the beginning of experiment, and gently lowered to 26 ± 1 0C until broilers reached 11 days of age. Findings: The study result indicated that after 6 days of feeding, their feed intake and body weight gain were not significantly different among groups of control and supplemented with Japanese pepper seeds. However, feed conversion ratio decreased significantly with feed of 1% Japanese pepper seeds against 2% in Japanese pepper seeds broilers (P&lt;0.05). Subsequently, all groups were subjected to high heat at 38o C, for 3 hours with water but not feed. The tendency was in wing drop and panting during temperature exposure groups (P&gt;0.05). With acute heat stress, the temperature of all groups was elevated. The effects of time and Japanese pepper seeds were significant (P&lt;0.05) in temperature exposed broilers. The interaction between time and Japanese pepper seeds were measured to reflect a tendency of significance (P&lt;0.01). The affinities were measured in rectal temperature of control group and 2.0% group of Japanese pepper seeds broilers to reduce after 2h, although they kept advancing in 1% group of Japanese pepper seeds. There were no significant differences in the level of plasma monoamines in 5- HT, Ad and NA among groups (P&gt;0.05), although the level of DA in plasma in 2% Japanese pepper seeds in broilers was lower than control one (P&lt;0.05). Conclusion: Present investigation recommend that Japanese pepper seeds affect thermoregulation through the catecholaminergic system in broilers. Nevertheless, it may have adverse effects under long period high temperature in chicks.

Monoamine Levels and Parkinson's Disease Progression: Evidence From a High-Performance Liquid Chromatography Study.

Parkinson’s disease (PD) is associated with dysfunction of monoamine neurotransmitter systems. We investigated changes in the levels of monoamine and their metabolites in PD patients, together with their association to clinical profiles. PD patients and age-matched control subjects (n = 40 per group) were enrolled. Using high-performance liquid chromatography (HPLC) with an electrochemical detector, levels of monoamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; and serotonin, 5-HT) were measured in plasma, while the metabolites (homovanillic acid, HVA; vanillylmandelic acid, VMA; and 5-hydroxyindoleacetic acid, 5-HIAA) were measured in urine. Plasma DA level was not significantly different between PD and control groups. PD patients had significantly higher plasma NE but lower EPI and 5-HT levels. PD patients had a significantly higher HVA/DA ratio and lower VMA/NE ratio than control subjects, while the 5-HIAA/5-HT ratio was not different between the groups. Regarding the association between monoamine levels and clinical profiles, the DA level had a negative relationship with disease duration and the 5-HT level had a negative relationship with severity of motor impairment. These findings emphasized the involvements of several neurotransmission systems and their association with clinical profiles in PD patients, demonstrated by quantification of monoamine levels in peripheral body fluids. This could benefit appropriate pharmacological treatment planning in respect of monoamine changes and might also help predict subsequent clinical symptoms.

Design, synthesis and biological evaluation of lazabemide derivatives as inhibitors of monoamine oxidase

In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B. It could be seen from the data of inhibition activity experiments in vitro, that the compound 3d was IC50 = 3.12 ± 0.05 μmol/mL of MAO-A and compound 3m was IC50 = 5.04 ± 0.06 μmol/mL. In vivo inhibition activity experiments were conducted to evaluate the inhibitory activity of compounds 3a, 3d, 3f, 3i and 3m by detecting the contents of 5-HT, NE, DA and activity of MAO-A and MAO-B in plasma and brain tissue. In vivo inhibition activity evaluation results showed that the compounds 3a, 3d, 3f, 3i and 3m had increased the contents of 5-HT, NE and DA in plasma and brain tissues. Meanwhile, the determination results activity of MAO in plasma and brain tissue showed that the compounds 3a, 3d, and 3f had a significant inhibitory effect on the activity of MAO-A, while the compounds 3i and 3m showed inhibitory effect on the activity of MAO-B. This study provided a new inhibitors for inhibiting of MAO activity.

Plasma Norepinephrine and Dopamine Levels in Prepubertal Male Children with Attention-Deficit Hyperactivity Disorder do not Change with 8 Weeks of Methylphenidate Treatment

ABS TRACT: Plasma norepinephrine and dopamine levels in prepubertal male children with attention-deficit hyperactivity disorder do not change with 8 weeks of methylphenidate treatment Objectives: The aim of this study was to determine plasma norepinephrine and dopamine levels at baseline and after 8 weeks of stimulant treatment in pre-pubertal male children with ADHD. Methods: The study group consisted of 50 children (6-12 years old) diagnosed with ADHD. The control group comprised students from a primary school within the epidemiological catchment area of the clinic and was matched for class and age to the ADHD patients. The Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) was used to diagnose ADHD and allowed comorbidities. Mental retardation was ruled out with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and impaired functioning. We evaluated disorder severity at the time of assessment using the Clinic Global Impression Scale (CGI). The DuPaul ADHD Rating Scale-IV (ARS) was also used. All patients were treatment-naive. The parents were advised to use OROS methylphenidate daily with no drug holidays during weekends. No rescue medications (immediate-release methylphenidate) were allowed. The dose started at 18 mg and was titrated to 54 mg in 4 weeks to yield average doses of 1 mg/kg/ day. Baseline and endpoint plasma DA and NE were measured. Results: Baseline plasma NE and DA levels had no statistically significant differences between ADHD patients `and controls (232.0±67.3 versus 232.2±65.3 pg/mL and 169.3±48.4 versus 186.9±40.5 pg/mL). Plasma NE levels in all ADHD subgroups decreased with 8 weeks of stimulant treatment, while changes in DA levels were more complex. Plasma DA levels decreased with treatment in the ADHD-inattentive subgroup but were elevated in the hyperactive/impulsive and combined subgroups. There were no statistically significant differences between ADHD subgroups for these variables. Endpoint NE levels were correlated with endpoint DA levels. There were no statistically significant differences between ADHD subgroups. Plasma NE levels were not related to symptom severity or treatment response. In contrast, baseline DA levels were negatively correlated with ARS total scores. Conclusions: We found no statistically significant differences between plasma levels of NE and DA in a prepubertal male sample with ADHD and controls. Plasma DA and NE levels were correlated at both baseline and the endpoint. Although there was a signal that baseline DA levels may correlate with ADHD symptoms as evaluated via ARS, this was not true for endpoint analyses. Because this negative correlation disappeared after treatment, this finding about baseline DA levels may also be evaluated as an early treatment neuromarker. The negative results could also be explained by our focus on plasma. The recent consensus is that urinary levels of NE and DA may be more informative in patients with ADHD and that concurrent evaluation of multiple neurotransmitter systems (i.e., neuropeptide Y and NE) may be more informative. Further studies may benefit from concurrent measurements of plasma and urinary levels of catecholamines and their metabolites.

Influence of mesenchymal stem cell transplantation on stereotypic behavior and dopamine of Tourette syndrome rats

Objective To investigate the effect of mesenchymal stem cell transplantation on stereotypic behavior and level of dopamine of Tourette syndrome(TS) rats. Methods Wistar rats were randomly divided into three groups namely sham group (microinfused with normal sera), TS group (microinfused with TS sera)group and TS plus MSC transplantation group. Auto-immune TS rat model were established and MSC suspension labeled with BrdU was injected into the striatum of TS rats. DA were measured by high performance liquid chromatography and electrochemical detection. Results TS rats with MSC grafts exhibited significantly decreased stereotypic behaviors(7d: 117.3±8.4, 14d: 94.8±7.9, 28d: 78.8±7.4)and level of DA in striatum(7d: (898.2±143.2)ng/g, 14d: (812.4±92.2)ng/g, 28d: (757.9±82.4)ng/g) at 7, 14 and 28 days after transplantation compared to model group((129.3±9.8, 116.5±8.5, 106.8±6.4; (1209.3±182.3) ng/g, (1033.5±114.7) ng/g, (994.8±112.6) ng/g, P<0.01). DA in plasma of TS rats with MSC grafts also decreased at 7 and 14 days(7 d: (530.2±86.2)ng/g vs (690.3±72.7) ng/g; 14d: (562.4±64.2) ng/g vs (689.4±83.9) ng/g, P<0.01). Conclusions Transplantation of MSC could reduce stereotypic behaviors in TS rats and regulate the metabolism of DA. Key words: Mesenchymal stem cell; Tourette syndrome; Stereotypic behaviors; Dopamine

A novel blood-based biomarker for detection of autism spectrum disorders

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass–charge (m/z) values of 2020±1, 1864±1 and 1978±1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD.

Quantitative analysis of Tenecteplase in rat plasma samples using LC–MS/MS as an alternative for ELISA

An LC–MS/MS method has been developed for the quantitative determination of a protein drug (Tenecteplase; M W 58,777 Da) in rat plasma. The protein was digested with trypsin without prior clean-up of the plasma sample, without the use of a label nor internal standard. A limited validation was performed to assess the linearity, the sensitivity and the specificity of the method. In addition, the developed method was applied to the quantitative analysis of Tenecteplase in rat plasma samples originating from a single-dose study in rats.

Mechanism of the delayed onset of action after intravenous amiodarone for treatment of ventricular arrhythmias

AbstractThe onset of action of intravenous amiodarone (AM) for treatment of ventricular arrhythmias often occurs after at least several hours' delay. To investigate the mechanism of this delayed action, we gave i.v. AM at an initial loading dose of 2.5 mg/kg or 5.0 mg/kg over 10 min, followed immediately by infusion of 7.5 μg/kg.min or 10 μg/kg.min for 20 h in eight dogs. The concentration of AM and its major metabolite, N‐desethylamiodarone (DA), in plasma and myocardial tissue were determined immediately after the loading dose and at 20 h after infusion, respectively, while electrophysiologic parameters were measured at the same times. The concentration of AM and DA in plasma were also determined serially. The results showed that the concentration of AM or DA in plasma or myocardial tissue rose to the peak level within 5–15 min after the loading dose, the sinus cycle length and AV conduction Wenckebach point measured at this time increased significantly relative to baseline (P&lt;0.05), while the ventricular effective refractory period (VERP) and ventricular exciting time (VET) at this time did not increase significantly (P&gt;0.05). The concentration of AM or DA in plasma declined rapidly during the continuous infusion period and remained at a stable low level until infusion stopped. The concentration of AM or DA in the myocardial tissue at 20 h after continuous infusion was lower than immediately after the loading dose. The sinus cycle length and AV conduction Wenckebach point were shortened close to the baseline level, while the VERP and VET were unchanged 20 h after infusion. The delayed onset of action for treatment of ventricular arrhythmias after i.v. administration of AM cannot be explained by higher concentration of AM or its metabolite in myocardial tissue. The specific mechanism(s) of action of i.v. AM in its control of arrhythmias remain to be determined. Drug Dev. Res. 58:145–148, 2003. © 2003 Wiley‐Liss, Inc.

Visible Sympathetic Activity as a Social Signal in Anolis carolinensis: Changes in Aggression and Plasma Catecholamines

Darkening of postorbital skin in Anolis carolinensis occurs during stressful situations and is stimulated by sympathetic activation of β2-adrenergic receptors via adrenal catecholamines. This eyespot forms more rapidly in dominant males during social interaction. Eyespot darkening (green to black) appears to function as a social signal communicating sympathetic activation and limiting aggressive interaction. To assess the value of the eyespot as a social signal, males were painted postorbitally with green, black, or red paint. Each male was exposed to a mirror following acclimation to the cage. The total number of aggressive displays toward the mirror image was greatest when eyespots were masked by green paint. In contrast, black or red artificial eyespots, regardless of size, inhibited biting behavior toward the mirror image. The most aggressive males, those who saw a reflected opponent with no eyespot (hidden with green paint), had significantly higher levels of all plasma catecholamines. These results suggest that A. carolinensis use information from the eyespot to assess their opponent's readiness to fight and thereby determine whether to be aggressive. Darkened eyespots are capable of inhibiting aggression, whereas aggressive displays from an opponent in the mirror without darkened eyespots do not. Darkened eyespots reflect rapid changes in plasma NE, DA, and Epi that may signal dominant social status.

The study of maternal and fetal plasma catecholamines levels during pregnancy and delivery.

To study maternal and fetal plasma levels of catecholamines (CA) during pregnancy and delivery, especially changes in CA levels during fetal distress and conditions of different modes of delivery. Maternal and fetal plasma NE, E and DA levels were determined by high performance liquid chromatography (HPLC) for 16 non-pregnant women, 19 cases of early pregnancy, 17 cases of mid pregnancy, late pregnancy, spontaneous vaginal delivery and 53 cases of cesarean section. Plasma NE and DA levels decreased gradually with the advance of gestational weeks, and levels of plasma NE were significantly lower than those of non-pregnant women (P < 0.05). The levels of plasma CA in patients who had elective cesarean section were significantly lower than those who had vaginal delivery and emergency cesarean section (P < 0.01). However, CA levels of the cord artery in the vaginal delivery group were significantly higher than those in the cesarean section group (P < 0.01). Vaginal delivery is better than cesarean section for the newborn. If cesarean section is necessary, it is best for the newborn after onset of labor.

Suppression of noradrenaline spillover by the dopamine prodrug gamma-L-glutamyl-L-dopa: a central effect?

The DA prodrug gamma-L-glutamyl-L-dopa (gludopa) has a high degree of renal selectivity with 2-step conversion to DA in the kidney. The effects of gludopa, with and without DA-2 receptor blockade, on renal and total noradrenaline (NA) spillover, were studied in two groups of rabbits. Eight rabbits received gludopa infusion (25 and 100 micrograms/kg/min and 8 received an infusion of gludopa and DA-2 receptor antagonist, YM-09151 (50 micrograms/kg i.v.). Renal and total NA spillover rates were measured by 3H-NA tracer method before and after gludopa infusion. Brain NA, DA, gludopa and L-dopa content were measured after gludopa infusion in 5 rabbits; control values for tissue catecholamine and drug levels were obtained in 5 untreated rabbits. Gludopa infusion markedly increased kidney DA content (300-fold) and DA excretion (6000-fold) but had little effect on plasma DA. It produced a dose-related fall in mean (+/- SEM) renal NA spillover (21.6 +/- 3.7 to 10.6 +/- 2.7, 7.2 +/- 2.7 ng/min, p < 0.01). Even greater falls were observed in total NA spillover after gludopa (43.1 +/- 10.2 to 19.7 +/- 3.4, 9.4 +/- 1.8 ng/min, p < 0.01). DA-2 receptor antagonism had no influence on the effects of gludopa on either renal or total NA spillover. Significant amounts of gludopa were detected in the brain after drug infusion (0.28 +/- 13 nmol/g brain tissue). Gludopa, a putative renal selective dopamine prodrug with effects mediated via DA-1 receptors also significantly inhibits both renal and extra-renal NA spillover. This effect is not a DA-2 effect but may be mediated centrally.

Some biological mechanisms of the inborn predisposition to alcoholism.

The children of alcoholism patients have a high biological risk of this illness, mental and emotional disorders, and behavioral disturbances. The offspring of white mongrel rats with chronic alcohol intoxication were investigated in order to study the neurochemical mechanisms of these phenomena. The content of DA in blood and blood plasma, the characteristics of GABA and the opiate receptors of the brain, the activity of DBH, COMT, MAO, the content of cAMP and cGMP in brain tissue, as well as the expression of the gene c-fos were studied. Changes in the brain content of DA and qualitative and quantitative changes in MAO (an increase and solubilization of MAO A and B activity in the liver) were identified in the offspring of alcoholic rats. A tendency was also observed in the brain toward a decrease in the activity of DBH and COMT and an increase in the activity of cAMP and cGMP. The baseline expression of the gene c-fos in the offspring of male alcoholic rats did not differ from the norm; however, a powerful increase in the expression of the gene c-fos did appear in response to the administration of 2 g/kg of ethanol, in the absence of this effect in the control. A view is presented on the significant role of changes in the functions of the DA system in the genesis of pathology in the offspring of parents with chronic alcohol intoxication, as well as on the possible influence of the prolonged consumption of alcohol on the function of the genome.

Metabolites in Plasma after Oral Administration of Dopamine ProdrugTA-870 and Dopamine to Dogs and Metabolism of TA-870 in in vitro.

TA-870のドーパミンプロドラッグとしての有効性を明らかにするために，TA-870およびドーパミン塩酸塩(DA)をイヌに経口投与し，血漿中の代謝物濃度をHPLCを用いて測定した．また，TA-870の各種動物でのin vitroにおける代謝について検討した．活性体である遊離型DAの最高血漿中濃度はTA-870投与時(33．5mg，71μmol/kg)で252ng/ml，DA投与時(13.5mg，71μmol/kg)で29ng/mlであり，TA-870投与時の方が約9倍高かった．逆にDA抱合体およびDOPACの濃度はDA投与時に高かった．これらの結果から，TA-870のカテコールおよびアミノ基に結合した保護基は，初回通過代謝による不活性化を軽減させているものと思われ，ドーパミンプロドラッグとしての有効性が示唆された．TA-870の血漿中エステラーゼによる加水分解はラット>モルモット≈家兎>ヒト>イヌの順に速かった．また，本薬物は血漿中ではDAに変換しないが，ラットの全血小腸壁および肝臓ホモジネートではDAに変換した．DAへの変換速度ぱ肝臓>小腸壁>血液の順に速かった．

Anesthetics, Pentobarbital Induced Reduction of Blood Pressure and Catecholamines in Brain and Plasma by the SHR and WKY

(1) Pentobarbital anesthesia induced reduction of BP and reduced specifically on CA as BP-controler in brain and plasma. (2) Plasma NE and DA in Cast-group were higher than these of Int-group suggesting interaction of androgen. (3) Plasma CA was significantly deffered depend upon the routes of blood collection, different locus and P-anesthesia.

The heterogeneity of dopamine involvement in essential hypertension.

Compared to control subjects, patients with essential hypertension (EH) had a decreased urinary DA:NE ratio and an overall increase in the total (free + sulfated) plasma sum of NE, E and DA. With age-matching, this elevation was found to be due to augmented levels of DA sulfate. When subdivided into borderline (labile) and stable EH groups, only the borderline EH patients had heightened plasma DA sulfate levels, enhanced urinary homovanillic acid excretion and tended to have plasma NE and PRA increases. Patients with stable EH had a hyporesponsive urinary DA and Na+ excretion as well as reduced PRA levels at the height of furosemide-induced natriuresis. These data are compatible with a hyperdopaminergic component of the hyperadrenergic state, more or less affecting patients with borderline EH in contrast to the hypodopaminergic features of subjects evolving into stable EH in whom the neurogenic component subsides. In both EH subgroups, urinary DA lagged behind NE excretion. Dopaminergic tone may indirectly affect endogenous DA-modulated renal, adrenal and vascular synaptic processes as well as their responses to exogenous Angiotensin II and DA, respectively.

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia.

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.

Dexamethasone increases plasma free dopamine in man

In man, unconjugated plasma DA is normally undetectable or present in minute amounts. Twelve medication-free volunteers received a 1 mg dose of dexamethasone which produced pronounced increases of plasma free DA but not of other catecholamines. Mean plasma free dopamine levels after dexamethasone at 8 a.m. (155 ± 102 pg/ml) and 4 p.m. (163 ± 70 pg/ml) were significantly higher ( p< 0.001) than those at 8 a.m. (50 ±18 pg/ml) and 4 p.m. (42 ± 7 pg/ml) before dexamethasone. Although the mechanism of increased dopaminergic activity after a dose of dexamethasone remains for future research, the data presented in this paper may explain the observations that corticosteroids lower prolactin levels and may induce psychiatric disturbances, as well as the finding that depressed patients with high postdexamethasone cortisol levels are frequently psychotic.

Die quantitative bestimmung von feprazon und einem feprazon-metaboliten in humanplasma nach hochleistungsflüssigkeitschromatographischer oder dünnschichtchromatographischer trennung

Determination of feprazone and one of its metabolites in human plasma after high-performance liquid chromatographic or thin-layer chromatographic separation Two procedures suitable for pharmacokinetic routine analysis are described for the simultaneous determination of feprazone and one of its metabolites (DA 3505) in plasma samples. After extraction from acidified plasma feprazone and DA 3505 are determined by measuring UV absorbance after thin-layer chromatographic (TLC) separation (reversed-phase TLC plates; methanol—water—formic acid) or high-performance liquid chromatographic (HPLC) separation (silica gel column; hexane—tetrahydrofuran—acetic acid). Limits of detection are 0.1 μg feprazone per ml plasma and 0.2 μg of its metabolite per ml plasma using the HPLC method. Concentrations down to about 0.5 μg/ml plasma of both compounds can be determined using the TLC method.

Is dopamine a neurohormone of the adrenal medulla? Studies with morphine stimulation.

Dopamine (da) concentrations in rat adrenals, plasma and brain were variably elevated 1 h after a large parenteral dose of morphine. In adrenals, unlabelled DA increased 2-fold and labelled DA, synthesized from 3H-tyrosine, increased more than 4-fold. The increases could be prevented by inhibition of DA-synthesizing enzymes and spinal cord transection, respectively. Labelled DA in plasma increased 2.7-fold after morphine in intact rats but did not increase in those with spinal cord transection. It is concluded that: (1) morphine stimulates the adrenal by increasing nerve impulse flow, (2) increased nerve impulse flow increases DA synthesis and levels, and (3) the increased DA levels result in increased release of DA into the bloodstream.