The effect of sodium restriction on iodine prophylaxis: a review.

PURPOSE: Sodium is essential to life. However, its dietary excess is detrimental to the cardiovascular system, and sodium restriction is a crucial step in cardiovascular prevention. Iodine deficiency has been fought worldwide for decades, and substantial success has been achieved introducing the use of iodine-enriched salt. Nevertheless, areas of iodine deficiency persist around the world, both in developing and industrialized countries, and a major concern affecting dietary sodium reduction programs is represented by a possible iodine intake deficiency. There are substantial differences in the source of alimentary iodine among countries, such as iodized salt added, household tap water, seafood, or salt employed in packaged food. It is clear that a sodium-restricted diet can induce differences in terms of iodine intake, depending on the country considered. Moreover, iodine status has undergone relevant changes in many countries in the last years. METHODS: Systematic review of literature evidence about the possible effects of sodium restriction on population iodine status. RESULTS: To date, the available results are conflicting, depending on country, salt iodization policy, as well as time frame of data collection. However, to ensure an optimal iodine supply by salt fortification, without exceeding the current recommendation by World Health Organization for salt intake, seems to be an achievable goal. CONCLUSION: A balanced approach may be obtained by an adequate iodine concentration in fortified salt and by promoting the availability of iodized salt for household consumption and food industry use. In this scenario, updated prospective studies are strongly needed.

In vitro antiproliferative effect of trastuzumab (Herceptin(®)) combined with cetuximab (Erbitux(®)) in a model of human non-small cell lung cancer expressing EGFR and HER2.

Lung cancer is the leading cause of cancer death. For this reason, new therapies are needed for the treatment of this devastating disease. In this study, we investigated the effects of combining cetuximab and the trastuzumab on the growth of a model of human non-small cell lung carcinoma cell line (A549). The results were compared with those obtained from a human lung squamous carcinoma cell line (NCI-H226). Both cell lines were treated with cetuximab and trastuzumab, alone or in combination, at various concentrations, for 24, 48 and 72 h. Cell proliferation was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. EGFR and HER-2 mRNA expression was detected by reverse transcription polymerase chain reaction, and the gene amplification status of receptors was evaluated by fluorescence in situ hybridisation. The colorimetric proliferation assay showed that trastuzumab combined with cetuximab significantly inhibited A549 cells at a dose of 40 µg/ml after 72 h of treatment (p < 0.05), while no time-dose dependent inhibition was observed in NCI-H226 cells. The combined treatment influenced both levels of EGFR and HER-2 mRNA in A549 cells and only EGFR mRNA levels in NCI-H226 cells. Fluorescence in situ hybridisation showed that both cell lines were aneuploid for the two genes with equally increased EGFR and CEN7 signals, as well as HER-2 and CEN17 signals, indicating a condition of polysomy without amplification. The preliminary results of this study encourage further investigations to elucidate the downstream events involved and to understand how these mechanisms influence non-small cell lung cancers growth.

In vitro combined treatment with cetuximab and trastuzumab inhibits growth of colon cancer cells.

OBJECTIVES: Overexpression or constitutive activation of epidermal growth factor receptors (EGFR) is involved in growth of human cancers. We investigated effects of EGFR and HER-2 blockade in colon cancer cell lines using cetuximab and trastuzumab, with the aim of developing novel approaches to cancer therapy. MATERIALS AND METHODS: We studied effects of treatment on cell growth, cell cycle distribution, induction of apoptosis, changes in EGFR and HER-2 mRNA-protein expression and EGFR and HER-2 gene copy number in Caco-2, HT-29 and HCT-116 cells. RESULTS: Treatment of cells resulted in no effect in one of the three cell lines and in inhibition of cell proliferation in a time- and dose-dependent manner in the other two, with modulation of EGFR and HER-2 mRNA and protein levels. Differences in sensitivity to cetuximab and trastuzumab were observed. Treatment induced specific changes in cell cycle distribution in both cell lines affected, while apoptosis was not increased. Fluorescence in situ hybridization analysis revealed abnormal copy number of two genes resulting from aneuploidy; this was not responsible for different sensitivity to combination between the two cell lines. CONCLUSIONS: Targeting EGFR and HER-2 simultaneously could have useful applications in colorectal cancer treatment. To improve pharmacological efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved in their activity need to be elucidated.

Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex.

BACKGROUND: Gap junctions are specialized channels composed of several connexins, membrane proteins that mediate electrical and metabolic coupling between cells. Previous data have suggested that changes in the expression of Cx43, the main astrocytic Cx isoform, may be involved in seizure activity in human epileptic tissue. However, Cx43 has never been examined in focal cortical dysplasia (FCD) and in other human refractory epilepsies. METHODS: We analyzed Cx43 protein localization and Cx43 mRNA levels in surgical specimens of cortex from a cohort of patients with intractable epilepsy vs control nonepileptic tissue. Samples had neuropathologically defined diagnosis of cryptogenic epilepsy or epilepsy secondary to FCD. RESULTS: Cx43 immunoreactivity, which labeled punctate elements, did not reveal distinctive features in cryptogenic epilepsy and FCD type IA and IIA. A peculiar pattern of immunolabeling was instead observed in FCD type IIB, in which large aggregates of Cx43-immunopositive puncta were clustered around subsets of balloon cells and astrocytes. Further characterization revealed that these balloon cells do not express markers of precursor cells, such as CD34. Quantitative real-time reverse transcriptase PCR showed elevated levels of Cx43 transcript in a subgroup (25%) of cryptogenic epilepsy specimens compared to control and FCD ones. CONCLUSIONS: Our study points out that a rearrangement of Cx43-positive elements is part of abnormal tissue organization in FCD type IIB, and that cryptogenic epilepsies include forms with increased Cx43 mRNA expression. The data implicate functional consequences of altered Cx43 expression, and therefore of altered gap junctional coupling, in abnormal network properties of subtypes of human refractory epilepsies.

Polymorphisms of steroid 5-alpha-reductase type I (SRD5A1) gene are associated to peripheral arterial disease.

Although animal studies support the hypothesis that androgenic biological actions may affect experimental atherosclerosis progression, evidence for a relationship between androgen effects and peripheral arterial disease (PAD), a common clinical form of atherosclerosis, is weak or contradictory. Testosterone, the main androgen hormone, is converted in a 5alpha-reduced form by enzymatic activities in the target cells and some specific actions are mediated by such metabolites. Steroid 5-alpha reductase isoenzymes (SRD5A1 and SRD5A2) catalyze the conversion to the bioactive potent androgen dihydrotestosterone and other reduced metabolites and represent relevant regulators of local hormonal actions. In the present study we tested for the association of selected single nucleotide polymorphisms (SNP) of SRD5A1 and SRD5A2 with symptomatic PAD patients. Two different SNP in the SRD5A1 were significantly associated which the PAD phenotype (p<0.03, odds ratio 1.73), while no association was found between PAD phenotypes and SRD5A2. Since the examined SRDA1 gene variant was previously associated with a low enzymatic activity, we suggest that a decreased local enzymatic conversion of testosterone may contribute to PAD genetic susceptibility.

Acetylcholine-induced, calcium-dependent norepinephrine outflow from peripheral human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes, as well as in the supernatants, after incubation with L-tyrosine and L-dihydroxyphenylalanine (L-Dopa) for 1 h. The effect that the addition of acetylcholine (ACh), Veratridine, lonomycin or KCI had on the outflow of norepinephrine (NE) from lymphocytes was also studied. The effect of the addition of methoxyverapamil (D600, a Ca2+ channel blocker) and cholinergic antagonists had on the ACh-induced NE outflow was assessed. CA were determined by HPLC-ECD, both in the supernatant and in the cell lysates. L-Tyrosine and L-Dopa significantly (P < 0.01) increased intracellular NE. Neither L-tyrosine, L-Dopa, nor vehicle induced a detectable outflow of NE to the supernatants. ACh [120 microM], Veratridine [100 microM], Ionomycin [10 microM] and KCl [50 mM] (with or without the simultaneous addition of L-tyrosine or L-Dopa) all induced a detectable outflow of NE to the supernatant when added 5 min before the end of incubation. NE was not detectable in the supernatant when the chemicals were added 10 to 20 min before the end of the incubation. When the chemicals were added at lower concentrations, erratic secretion or no secretion whatsoever was observed. D600 [100 microM] was able to significantly (P < 0.01) reduce the ACh-induced NE outflow. Tetraethylammonium (nicotinic antagonist), but not atropine (muscarinic antagonist), significantly (P < 0.001) decreased the ACh-induced NE outflow. The outflow of NE from peripheral human lymphocytes was seen. NE secretion seems to be ACh- and calcium-dependent since Veratridine, Ionomycin and KCl are able to induce Ca2+ entry by means of various mechanisms. The Ca2+ channel blocker employed in this study (D600) reduced the ACh-dependent NE outflow. We can conclude that both ACh (through nicotinic receptors) and calcium are involved in the outflow of NE from peripheral human lymphocytes.

Ambulatory blood pressure monitoring: how reproducible is it?

We tested the reproducibility of ambulatory blood pressure monitoring (ABPM) by the use of agreement plots. Thirty-two normotensive volunteers underwent ABPM on four separate days (interval 28 days), on the same typical weekday. Sleeping time was restricted to the ABPM nighttime subperiod from 11:00 PM to 7:00 AM. Twenty-four-hour average values-both systolic and diastolic-daytime average values, and nighttime average values, as well as standard deviation (SD) values, were analyzed for differences (analysis of variance). Adaptation occurred from the first to the fourth ABPM, ie, average 24 h, daytime, and nighttime values were lower (-1 to -3 mm Hg) during the fourth recording than the first (P < .05 to P < .01). The agreement analysis showed a surprisingly high agreement among the four data sets (ie, differences from +/-2.54 to +/-5.92 mm Hg; +/-2 SD of the distribution). We concluded that reproducibility of ABPM seems excellent, but adaptation may occur, even in normotensive volunteers under research conditions. Caution must be paid before labeling a patient as hypertensive, because initial ABPM may yield higher values than later monitorings.

L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes in basal conditions as well as after L-tyrosine and/or acetylcholine (ACh) stimulation. Nicotinic and muscarinic receptor activation and blockade were assessed. CA were determined after ultrasonic cell disruption in peripheral lymphocytes after incubation (1 h at 37 degrees C) with the chemicals employed. L-tyrosine significantly increased (P < 0.01) L-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low microM range did not modify, whereas ACh (60 microM) and (120 microM) significantly increased (P < 0.01), both L-Dopa and NE intracellular levels. L-tyrosine plus ACh (60 microM) or (120 microM) significantly increased (P < 0.01) intracellular L-Dopa and NE versus control, versus L-tyrosine alone and versus ACh alone. The increase was higher than the algebraic sum of the individual increases. Nicotine (250 microM), but not muscarine (50 microM), significantly increased L-Dopa and NE in lymphocytes. Tetraethylammonium (500 microM) (nicotinic blocker), but not atropine (100 microM) (muscarinic blocker), inhibited the ACh-mediated increase of intracellular L-Dopa and NE. These data show that lymphocyte synthesis of CA is under nicotinic control. Since intracellular L-Dopa after L-tyrosine plus ACh increased 6-fold versus basal, 2-fold versus L-tyrosine alone and 3-fold versus ACh alone, it is concluded that ACh might regulate CA synthesis in lymphocytes through an activation of the rate limiting enzyme tyrosine hydroxylase.

Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes.

We studied the catecholamine (CA) content in peripheral human lymphocytes and the ability of these cells to synthesize CA in vitro. CA were separated by high performance liquid chromatography (HPLC) and determined in the supernatant by electrochemical detection as well as being determined after ultrasonic cell disruption in mononuclear leukocytes, adherent cells (monocytes/macrophages), total lymphocytes, and B- and T-cell enriched fractions. T lymphocytes contained L-Dopa and norepinephrine (NE), whereas B lymphocytes contained only L-Dopa. Lymphocytes seem to be able to synthesize NE from both L-tyrosine and L-Dopa added to the incubation medium in concentrations similar to the peripheral venous plasma (i.e. 5 x 10(-5) m and 10(-8) m, respectively). The addition of D-Dopa did not increase intracellular NE. alpha-methyl-p-L-tyrosine, benserazide, disulfiram, and fusaric acid (which are inhibitors of the enzymatic pathway) all decreased the synthesis of NE. After the addition of [3H]-L-Dopa (10(-8) m and 10(-7) m) to the incubation medium, [3H]-NE and [3H]-dopamine appeared. By increasing the concentration of L-Dopa in the medium (< 10(-6) m), CA were detected in the supernatant as well. These data show that peripheral human T lymphocytes contain and are able to synthesize CA from normal precursors in physiologic concentrations, i.e. a CA synthetic pathway is shown in nonneural cells. These data seem to support the hypothesis of autocrine and paracrine loops in the regulation of lymphocyte activity in lymphocytes taken from human cerebrospinal fluid (as suggested by other authors).

Blood pressure evaluation by noninvasive and traditional methods. Consistencies and discrepancies among photoplethysmomanometry, office sphygmomanometry, and ambulatory monitoring. Effects of blood pressure measurement.

Three hundred eight outpatients referred for hypertension were studied. A continuous beat-to-beat noninvasive recording (Finapres) of blood pressure evaluated the blood pressure increase (9 mm Hg systolic and 4 mm Hg diastolic) induced by office sphygmomanometry. Thereafter, patients underwent a 24-h ambulatory blood pressure monitoring. The evaluation against Finapres showed that office sphygmomanometry overestimates the systolic blood pressure by 3 +/- 36 mm Hg (mean +/- 2 SD) and the diastolic blood pressure by 15 +/- 25 mm Hg (mean +/- 2 SD). Blood pressure monitoring showed similar discrepancies. On the basis of both monitoring (normalcy defined from a population of 550 normotensive subjects) and office sphygmomanometry, patients were considered normotensive, hypertensive (either untreated or under active drug treatment), white coat hypertensive (monitoring below the 95th percentile and sphygmomanometry more than 140/90 mm Hg, either untreated or under active drug treatment), and reverse white coat patients (monitoring over the 95th percentile and sphygmomanometry less than 140/90 mm Hg). Patients showed different levels of alert reaction (the highest in white coat hypertensive and the lowest in reverse white coat hypertensive patients), and a similar increase in blood pressure induced by conventional sphygmomanometry. During initial readings of ambulatory monitoring, blood pressure decreased from the first reading to the third reading. This decrease is related to the increase of blood pressure under sphygmomanometry. Caution should be paid in interpreting results of sphygmomanometry (error level in the single patient as high as +/- 40 mm Hg), and interpreting and averaging results of the first hour of blood pressure monitoring (variably affected by the alert reaction to the clinical environment).

Yohimbine effects on blood pressure and plasma catecholamines in human hypertension.

The purpose of this study has been to test the hypothesis of an alpha 2-adrenoreceptor alteration in human essential hypertension. The design of the study involved the oral administration of 10 mg yohimbine, an alpha 2-adrenergic antagonist, to 25 healthy volunteers and 29 sex- and age-matched untreated hypertensive patients. Volunteers and patients were studied twice in random order, after placebo or yohimbine treatment, in supine and upright positions. Arterial pressure and heart rate were monitored by servoplethysmomanometry, and venous plasma catecholamines were determined by HPLC with electrochemical detection. Yohimbine induced a significant increase in diastolic pressure only in the hypertensive patients. Plasma norepinephrine was increased significantly in both yohimbine-treated groups, but the percent increase of plasma norepinephrine after the standing test was decreased significantly only in the healthy yohimbine-treated subjects. Plasma dopamine was increased significantly only in the healthy yohimbine-treated subjects. The response of plasma dopamine to the upright position was modified only in the healthy yohimbine-treated subjects. The decrease observed after 2 min of standing was abolished, showing the involvement of alpha 2-adrenoreceptors in the physiologic response of plasma catecholamines in healthy volunteers. Our data may be consistent with some in vivo evidence of an alpha 2-adrenoreceptor desensitization or an alteration in the balance of alpha-adrenoreceptors in human hypertension.

Effects of opioid substances on cAMP response to the beta-adrenergic agonist isoproterenol in human mononuclear leukocytes.

The effects of different opioid substances on isoproterenol and forskolin-stimulated cyclic AMP (cAMP) intracellular accumulation, and on the binding of 125I-pindodol (IPIN) to beta 2-adrenoceptors were studied in human mononuclear leukocytes (MNL). The opioids used were alpha-endorphin, beta-endorphin, tau-endorphin, DAGO (a mu receptor agonist), dermenkephalin (a delta receptor agonist and morphine. Only morphine was able to increase the cAMP response to isoproterenol. The EC50 of isoproterenol for cAMP accumulation was shifted leftward by morphine; this effect was blocked by naloxone. On the contrary, the cAMP response to forskolin, direct activator of adenylate cyclase, was similar in the control test with respect to the experiments with morphine. The five opioid peptides induced no changes in the dose-response curves with isoproterenol and forskolin. Furthermore, none of the opioids induced changes in the IPIN binding. Our data show that morphine is able to exert a significant enhancement of the response of beta 2-adrenergic receptors to isoproterenol in human mononuclear leukocytes. This effect seems to be mediated by mu opioid receptors and seems to involve G protein.

Evidence for interactions between HLA system class I and beta-adrenergic receptors in human mononuclear leukocytes.

In order to determine the possible interactions between histocompatibility leukocyte antigen (HLA) -class I antigens and beta-adrenergic receptors, we evaluated the effects of anti-HLA class I monoclonal antibodies on beta-adrenoceptor-mediated intracellular production of cAMP in human mononuclear leukocytes. Moreover, we studied whether anti-HLA class I monoclonal antibodies inhibit the binding of a specific radioligand to the beta-adrenoceptors, and, conversely, whether both isoproterenol and propranolol interfere with the binding (evaluated by a cytofluorometric assay) of the anti-HLA class I monoclonal antibodies to the cell membrane. Our results showed that anti-HLA class I monoclonal antibodies induced a significant beta-adrenergic-dependent increase in intracellular cAMP whereas anti-HLA class II and antimelanoma monoclonal antibodies were ineffective. Moreover anti-HLA class I monoclonal antibodies inhibited, in part, the specific binding of a beta-adrenergic radioligand, although they did not induce the internalization of the beta-adrenoceptors. On the other hand, both isoproterenol and propranolol induced a significant decrease in the peripheral blood mononuclear cell expression of HLA-class I molecules. Our data suggest that important interactions between major histocompatibility complex gene products and the beta-adrenergic receptors may occur in human cells.

Norepinephrine-induced plasma dopamine decrease in man: pharmacological evidence of the involvement of alpha 2-adrenoceptors.

OBJECTIVE: The purposes of this study were: (1) to test whether intravenous infusion of norepinephrine can affect plasma dopamine levels; and (2) to explore to what extent dopamine-2 or alpha 2-receptors play a role in this response. DESIGN: Norepinephrine infusion in man was performed to test whether the increase in norepinephrine during sympathetic stimulation can affect dopamine release. Specific antagonists of presynaptic dopamine-2 and alpha 2-receptors were administered to test the receptor(s) involved in this possible regulatory phenomenon. METHODS: Plasma catecholamine levels were investigated in seven normal subjects before and after administration of domperidone (dopamine-2 antagonist), yohimbine (alpha 2-antagonist) and norepinephrine. RESULTS: Both oral domperidone and yohimbine induced a significant increase in both plasma norepinephrine and plasma dopamine. Norepinephrine infusion induced a significant decrease in plasma dopamine. Pretreatment with domperidone only partially counteracted this inhibitory effect of norepinephrine infusion, whereas yohimbine fully counteracted it. CONCLUSIONS: Our data show that norepinephrine may act as a hormone at plasma concentrations as low as 450 pg/ml. The norepinephrine-induced plasma dopamine decrease seems to be alpha 2-adrenoceptor-mediated. This norepinephrine effect may be involved in the physiologic decrease in plasma dopamine that we demonstrated in the upright position in normal subjects.

Effects of intravenous epinine administration on left ventricular systolic performance, coronary hemodynamics, and circulating catecholamines in patients with heart failure.

Twenty-six patients with mild to moderate heart failure were studied to determine the effects of epinine infusion (at a rate producing plasma levels similar to those measured after oral administration of 100 mg of the prodrug ibopamine) on left ventricular (LV) function (14 patients), and coronary flow and circulating catecholamines (12 patients). The only significant hemodynamic change at an infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5-1 microgram/kg/min produced no significant changes in coronary blood flow or myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE) and dopamine (DA) levels decreased slightly and arterial and coronary sinus epinephrine increased. In conclusion, epinine, at concentrations similar to those achieved during therapeutic use of ibopamine, had negligible effect on myocardial contractility and relaxation rate in heart failure patients. Cardiac pump function was improved by a decrease in SVR rather than by inotropic stimulation. The data also suggest that these low concentrations of epinine may modulate the sympathetic nervous system, but further studies are needed to determine whether this effect could have clinical significance.

Intraindividual variation of beta 2-adrenergic receptors on mononuclear leukocytes and their relationships with endogenous plasma catecholamines in man.

The interindividual and intraindividual variations of both MNL beta 2-adrenergic receptor density and dissociation constant of binding were evaluated in 19 healthy volunteers. In addition the possible relationships between catecholamine plasma levels and MNL beta 2-adrenergic receptor density were studied in 8 of these subjects. The volunteers were studied three times with ten days' interval. There was a significant inverse relationship between receptor density and norepinephrine plasma levels, only. Neither epinephrine nor dopamine were correlated with receptor density. Interindividual coefficient of variation was 29.57%. The mean value of the intraindividual coefficients of variation was 14.1%, while the mean value of the analytical coefficients of variation was 10%. Our results are at some variance with data in the literature and may contribute to elucidate the role of MNL beta 2-adrenergic receptors as an index of sympathetic function in man.

Absence of correlations between plasma catecholamine levels and mononuclear leukocyte beta 2-adrenergic receptors in the elderly.

To assess the effects of aging on catecholamine plasma levels and mononuclear leukocyte (NML) beta 2-adrenergic receptors and on the possible relationships between these two parameters, we evaluated two groups of human subjects: 18 elderly volunteers (age 65-70 years) and 13 young volunteers (age 21-35 years). Norepinephrine plasma levels were significantly higher in the elderly subjects compared to the younger ones (P less than 0.05), whereas plasma epinephrine levels were not different. Also MNL beta 2-adrenoceptor density was significantly higher in elderly subjects (P less than 0.05). The binding dissociation constants were not significantly different. In young subjects there was a significant (P less than 0.02), inverse relationship between receptor densities and plasma norepinephrine levels; this relationship was not present in elderly persons. Our data suggest that the increase in beta 2-adrenoceptors may be due to a compensatory phenomenon, owing to the reduced beta-adrenergic sensitivity observed in the elderly subjects; moreover, the regulation of beta-adrenoceptors by plasma catecholamines seems to be altered by aging.

Neuroendocrine effects of interferon alpha 2-a in healthy human subjects.

The acute effects of interferon alpha-2a (3 x 10 IU im) on catecholamine and immunoreactive beta endorphin plasma levels, cortisol serum levels and lymphocyte beta 2-adrenoceptor density were evaluated in ten healthy volunteers. Interferon induced a significant increase in plasma norepinephrine; there was an increased norepinephrine standing response, too. On the contrary, epinephrine standing response was reduced by interferon. Lymphocyte beta 2-adrenoceptors decreased significantly after interferon administration; dissociation constant of binding was unchanged. Cortisol serum levels increased significantly with respect to control test, whereas immunoreactive beta endorphin did not change. These results support the hypothesis of functional relationships between neuroendocrine and immune systems; moreover they may be useful in clinical trials given the administration of interferon alpha in an increasing number of diseases.

Plasma dopamine response to sympathetic activation in man: a biphasic pattern.

We studied the plasma catecholamine response to standing and bicycle ergometric tests in 16 normal male subjects. During the standing test (performed in 10 subjects), we observed an early increase in plasma dopamine together with the fast increase in norepinephrine values; in the second half of this test (i.e. from 5 to 10 min of standing), we observed an increase in plasma dopamine levels. During the ergometric test (performed in 6 subjects), we observed a plasma dopamine increase at the maximal exercise; this persisted during the early recumbent recovery phase (6 min), despite the clear-cut decrease of both norepinephrine and epinephrine plasma levels. Our data are not in agreement with previous papers describing a simple increase in plasma dopamine after stimulation. This paper provides no informations regarding the mechanisms of this response of plasma dopamine. Other approaches must be used to study this aspect more directly.