Age-associated changes of exercise-induced plasma catecholamine responses

Age-associated plasma catecholamine responses were evaluated in 10 young (25 +/- 3 years) and 11 older competition cyclists (66.2 +/- 6 years) during incremental ergometric cycling. Noradrenaline levels were higher in the older subjects at rest, at identical work loads and at exhaustion. Adrenaline levels were similar in both groups at rest, higher in the old test subjects at identical work loads and lower in the old subjects at exhaustion. The noradrenaline-adrenaline ratio changed significantly depending on age from 5.1 +/- 0.5 to 8.7 +/- 2.1 which indicated higher adrenaline-related noradrenaline responses. The observed age-related differences may be caused by a compensatory mechanism which depends both on negatively age-correlated physical fitness, and on the decreased sensitivity of the organism to beta-adrenergic stimulation with age, as well as on an age-dependent change in the clearance of catecholamines from the circulation as described by Esler et al. (1981).     

Chemical ionisation mass fragmentographic measurement of dothiepin plasma concentrations following a single oral dose in man

A method is described for the measurement of the antidepressant drug dothiepin in human plasma.The procedure involves the addition of deuterodothiepin as an internal standard, extraction and measurement by chemical ionisation mass fragmentography. The minimum measurable concentration of 0.5 ng/ml enabled the pharmacokinetics of dothiepin in man to be studied after a single oral dose of 75 mg of dothiepin hydrochloride.Unlike other tricyclic antidepressants the apparent half-life of elimination (approximately 24 h) showed very little intersubject variation. However, the apparent volume of distribution was much more variable and could account for the wide range of steady state concentrations which have been found in patients taking dothiepin.     

Reproducibility of plasma catecholamine concentrations at rest and during exercise in man

The purpose of this study was to test the reproducibility of plasma norepinephrine (NE) and epinephrine (E) concentrations, at rest and during exercise, in man. Twelve young men were evaluated on two occasions (one week apart) at rest in supine and sitting positions and during dynamic exercise on bicycle ergometer: 5 min at a low intensity workload (heart rate = 131-133 bt min-1) and 5 and 20 min at a higher intensity (174-175 bt min-1). Mean plasma NE and E concentrations were not significantly different (p less than 0.05) on the two occasions in any of the experimental situations. However large within-subject variations were present, and the "standard errors of a single measurement" corrected for the variability of the catecholamine assay, ranged from 14 to 50% for NE and 14 to 37% for E. These results indicate that the mean plasma NE and E concentrations observed in a group of subjects are reproducible from one week to the other, but that individual plasma NE and E concentrations are not. This lack of reliability of a single determination of plasma catecholamine concentrations might be due to cyclic variations of plasma NE and E concentrations over time.     

Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain

The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guineapig brain. Guinea-pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxoneprecipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined.     

Effects of adrenergic blockade on plasma catecholamine levels during adrenaline infusion.

Alpha and beta adrenergic blocking drugs were administered, either singly or in combination, prior to a 3hr adrenaline infusion (2 microgram kg body wt-1 min-1)), Animals were premediated with either phenoxybenzamine (1 mg kg body wt-1 min-1). Phenoxybenzamine did not affect circulating adrenaline levels, but propranolol, either alone or in combination with phenoxybenzamine, resulted in a significant reduction in plasma adrenaline levels when compared with the control unblocked situation of adrenaline infusion without premedication. The results provide a possible explanation for the protective effect of combined adrenergic blockade in shock situations.     

The determination of the vitamin D metabolites on a single plasma sample: changes during parturition in dairy cows.

Methods have been developed for the precise measurement of the major known vitamin D metabolites in a single sample of cow plasma (~5 ml). The procedure involves initial extraction with methylene chloride-methanol followed by chromatography on Sephadex LH-20. 25-Hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined using high-pressure liquid chromatography and comparing ultraviolet absorption peak height with absorption peak heights of standards. The dihydroxylated metabolites were further purified and resolved by high-pressure liquid chromatography and determined by radioligand binding assays. The assays were employed to measure the total vitamin D metabolite levels in the plasma of paretic and normal dairy cows at parturition. Parturition had no effect on 25-hydroxyvitamin D levels in either group of cows (paretic, 37–44 ng/ml; normal, 35–38 ng/ml). However, normal cows did show lower mean 25-hydroxyvitamin D levels at every sampling period with the lowest levels in both groups occurring at 7 days postpartum. Plasma 25, 26-dihydroxyvitamin D was higher in paretic animals prepartum and at parturition (0.7–1.0 ng/ml) when compared to nonparetic animals (0.4–0.45 ng/ml). Similar levels (0.6 ng/ml) were observed in both groups postpartum. Cows developing parturient paresis showed a significant (P < 0.05) elevation of 1,25-dihydroxyvitamin D at parturition with a maximum level of 350 pg/ml attained at 1 day postpartum compared to prepartum levels of 60 pg/ml. Normal animals also showed a rise in plasma levels of 1,25-dihydroxyvitamin D with a maximum level of 185 pg/ml observed at 1 day postpartum. Plasma 24,25-dihydroxyvitamin D was initially higher in paretic cows (1.9 ng/ml) with a significant (P < 0.05) drop to 1.05 ng/ml occurring at parturition. This level was maintained for 7 days postpartum. The levels of this steroid were maintained at 1.3–1.4 ng/ml in the normal cows throughout the entire sampling period.     

Electrical stimulation of the median eminence in rats,changes in catecholamine content and in plasma prolactin and growth hormone concentrations

Effects of field stimulation of the medial basal hypothalamus (MBH) and coaxial stimulation of the median eminence was studied on the catecholamine and DOPAC levels of the median eminence and on the prolactin and growth hormone release. The field stimulation induced an increased prolactin and growth hormone secretion without altering the catecholamine and DOPAC level. The direct electrical stimulation of the median eminence reduced the noradrenaline and dopamine content without significant changes in DOPAC concentration and in hormone secretions. It is concluded that (1) variations of DOPAC content are inadequate indicators of neuronal activity in the median eminence; (2) the multiple interaction of the stimulated neurons in the median eminence may mask the expected biochemical and hormonal responses to electrical stimulation.     

Cyclic changes of plasma spermine concentrations in women

Based on previous studies which suggest that blood polyamines fluctuate during the menstrual cycle, the present study was set to determine whether plasma concentrations of the polyamine spermine show menstrual cycle-associated changes and if so, how these changes relate to phasic variations in other female hormones. Blood samples were collected from a group of 9 healthy women of various ages at 5 defined periods during their menstrual cycle including 1 woman on oral contraceptives. Spermine concentrations were determined in plasma acid extracts by reversed-phase high performance liquid chromatography method. Plasma estradiol, LH and FSH were measured by microparticle enzyme immunoassay using an automatic analyzer. Spermine concentrations, 104.4 +/- 12.2 nmol/ml at 1-3 day of the cycle, were increased transiently with a peak (263.8 +/- 22.1 nmol/ml) at 8-10 day and declined to 85.4 +/- 29.8 nmol/ml by 21-23 day of the cycle. The peak spermine concentrations coincided with the first increase in plasma estrogen levels. The individual variations in the temporal profile of spermine concentrations were of similar magnitude as individual differences in other female hormones. We conclude that: a) Plasma spermine concentrations undergo distinct cyclic alterations during the menstrual cycle with peak concentrations coinciding with the first estradiol increase, and b) Peak plasma spermine concentrations occur during the follicular phase, just prior to ovulation, during the period of rapid endometrial growth.     

Tissue glycogen concentrations in hypophysectomized pig fetuses following infusion with cortisol

The role of cortisol as a factor controlling the deposition of glycogen in the pig fetus was examined by infusing either a low dose (1 mg/day) or a high dose (3 mg/day) of cortisol into chronically-catheterized hypophysectomized fetal pigs for five days beginning on day 100-104 of gestation. After infusion, liver glycogen was significantly higher (P less than 0.05) and lung glycogen significantly lower (P less than 0.05) than in uninfused hypophysectomized litter mates although concentrations were significantly different from intact litter mates (P less than 0.05). Although skeletal and cardiac muscle content increased after infusion this difference was not significant. Changes in tissue glycogen content were similar for both the low and high rates of infusion. These observations indicate that exogenous cortisol alone is able to stimulate liver glycogen deposition and reverse the effect of hypophysectomy. Although other factors may be necessary for maximal response this suggests that cortisol is an important stimulant for liver glycogen deposition in the fetal pig. The effect of cortisol on muscle glycogen was equivocal suggesting that other hormones may play a more important role in this tissue.     

Urinary excretion of MPTP and its primary metabolites in mice

Mice were injected with single doses of MPTP (15 mg/kg, s.c.) containing one microCi of [3H]methyl-MPTP. Approximately 42% of the total injected [3H] was detected in the urine within 3 hours after drug administration. The early urine samples were analyzed using high pressure liquid chromatography. MPTP N-oxide was identified as a major metabolite, with trace amounts of MPP+ and MPTP also detected. The urinary volume and excretion of MPTP metabolites were inhibited by pretreating the animals with probenecid (250 mg/kg, i.p.). These results indicate that large amounts of injected MPTP are rapidly metabolized in the periphery by liver enzymes to form MPTP N-oxide.     

The effect of a six-day ski-hike on plasma catecholamine concentrations and on their response to submaximal exercise

Plasma catecholamine concentrations and dopamine-beta-hydroxylase activities were studied in 29 participants of a six-day cross-country ski-hike (260 km) to elucidate the adaptive responses of the sympatho-adrenal system to prolonged heavy exercise. Immediately after skiing on the first skiing day plasma noradrenaline concentrations appeared to be over twice as high as in the morning. On the morning of the fourth day noradrenaline levels had increased significantly when compared to those of the first morning. Concentrations after skiing on the fourth day were, however, about the same as in the first evening. After a submaximal ergometer test performed immediately after the skiing concentrations were still raised and the relative enhancement by this short-term exercise was about the same magnitude (40--60 %) on every test day. On the sixth day noradrenaline concentrations were about the same level as on the fourth day. Eleven days after the hike the basal noradrenaline levels were still about 25 % higher than before it. The changes of plasma adrenaline concentrations were in the same direction although not as striking as those of noradrenaline. Dopamine alterations were negligible. A significant but reversible decrease in plasma dopamine-beta-hydroxylase activities and cholesterol concentrations was found during the hike. The present results show that the sympatho-adrenal system is activated during the first few days of a ski-hike type prolonged exercise. A plateau developed in about four days. There were no signs of a decreased sympatho-adrenal response to a short-term heavy load.     

Serological changes following a single intravenous Corynebacterium parvum injection in the rat

Summary Changes in circulating levels of immunoglobulins (IgM and IgG), C3, acute-phase reactants, total protein, albumin, iron, and indicators of hepatic and renal function were monitored for up to 3 weeks after a single IV Corynebacterium parvum (C. parvum) injection. In addition to a marked increase in immunoglobulins, there was also evidence of complement activation and of tissue injury typified by a classic acute phase response in levels of ₂-macroglobulin and fibrinogen.A fall in total protein and albumin levels was observed during the first 2 days after C. parvum administration, and significant decreases in serum iron also occurred within the first 4 days. In contrast, increases in serum transaminase and alkaline phosphatase activity were consistent with hepatic injury. Furthermore, raised levels of urea and creatinine suggested mild impairment of renal function.These results indicate the need for serial, serological monitoring of immunological, hepatic and renal function during systemic immunotherapy with C. parvum.     

Temporal changes in metabolites of prostanoids in milk of heifers after intramammary infusion of organisms

A study was conducted to characterize the changes in the concentrations of three metabolites of prostanoids in the milk of a) heifers (n=14; control) inoculated with ( ) organisms into the udder and b) in heifers (n=10; treatment) vaccinated heifers. Milk samples were obtained from the challenged quarter and analyzed for the concentrations of stable metabolites of thromboxane A₂ (TXB₂), concentrations were significantly higher (P=0.03)bar compared to treated heifers. Milk PCM concentrations increased significantly (P=0.02) in control and treated heifers after the respective treatments, however, differences between the two groups were not significant. Milk PGEM concentrations also increased significantly (P=0.02) in control and treated heifers after the respective treatments, and there were no differences between the two groups. Results of the present study suggest that, the prostanoids have a role in the pathophysiologic process of coliform mastitis     

Acute changes in plasma renin activity, plasma aldosterone concentration and plasma electrolyte concentrations following furosemide administration in patients with congestive heart failure--interrelationships and diuretic response

We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling.     

Identification of lipoprotein X-like particles in rat plasma following Intralipid infusion.

Fasting rats were infused with 10% Intralipid for 24 h (0.33 mL/h per 100 g body weight) and the plasma lipoproteins isolated and compared with those of fed animals and animals with bile duct ligatures as controls. There was a 6- to 10-fold increase in the free cholesterol and phospholipid content of total plasma in animals infused with Intralipid or with ligated bile ducts. The changes were largely restricted to the low density lipoproteins (d=1.019--1.063 g/mL) where free cholesterol and phospholipid increased 30- to 60-fold compared with fed control animals. Hydroxylapatite chromatography of the low density lipoprotein fractions of both Intralipid-infused and bile duct ligated animals yielded a subfraction which was rich in free cholesterol (27%), phosphatidylcholine (66%), and protein (6%); the latter was composed primarily of albumin and apo C proteins. The electrophoretic mobility and polyanionic precipitation properties of the abnormal lipoprotein were indistinguishable from those of lipoprotein X isolated from the animals with bile duct ligatures. The albumin in the abnormal lipoprotein from both groups of experimental animals was detected immunochemically only after delipidation of the lipoprotein. Twice as much of the lipoprotein X accumulated in Intralipid-infused than in the bile duct ligated animals. On rechromatography of the residual low density lipoprotein other subfractions could be isolated which possessed lipid and protein proportions intermediate between those of the lipoprotein X and of normal rat plasma low density lipoprotein. The activity of lecithin cholesterol acyl transferase was increased twofold in the Intralipid-infused animals when compared with control animals, but it decreased by 50% in the animals with bile duct ligatures. It is concluded that the unusual lipoprotein X accumulates in the plasma of Intralipid-infused animals owing to incomplete clearance of the exogenous phospholipid, which mobilized tissue cholesterol and in the form of vesicular particles serves as a lipid phase for apo C proteins. A comparable mechanism is suggested for the formation of lipoprotein X in the animals with bile duct ligature.     

Seasonal variation in blood concentrations of interleukin-6, adrenocorticotrophic hormone,metabolites of catecholamine and cortisol in healthy volunteers

We investigated seasonal changes in blood concentrations of interleukin-6 (IL-6), adrenocorticotrophic hormone (ACTH), metabolites of catecholamine (VMA, HVA, and 5-HIAA) and cortisol in humans. Eight volunteers were investigated at four times during the year (February, May, August and October) at latitude 35° N. The mean ambient temperature at the collection periods was higher in the order of summer > autumn ≈ spring > winter. Changes in mood were also monitored by a profile of mood states (POMS) questionnaire. The concentration of IL-6 was significantly higher in winter and summer than in spring and autumn. The concentrations of ACTH, HVA and VMA were significantly higher in summer. No seasonal variation was detected in cortisol. There were significant differences among the seasons in subscale tension and anger in the POMS questionnaire; the tension subscale showed significant differences between spring and autumn, with a higher score in spring. The results demonstrate that Il-6, ACTH, HVA and VMA exhibit statistically significant seasonal rhythms, which might have important diagnostic and therapeutic implications.