Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 19 recordsLinked to original sources

PubMed1992

Time-dependent anticonvulsant activity of melatonin in hamsters.

The objective of the present study was to assess whether the anticonvulsant activity of melatonin displays diurnal variability in hamsters. Convulsions were induced by administering 3-mercaptopropionic acid (3-MP). There was a significant diurnal variation in 3-MP-induced convulsions, hamsters being more prone to exhibit seizures during the night than during the day. Melatonin (50 mg/kg i.p.) had a maximal anticonvulsive effect in the early evening (20:00 h). The administration at 20:00 h of the central-type benzodiazepine antagonist, Ro 15-1788, although unable by itself to modify seizure threshold, blunted the anticonvulsant response to melatonin. The results indicate that the time-dependent anticonvulsant activity of melatonin is sensitive to central-type benzodiazepine antagonism.

3-Mercaptopropionic Acid↗

PubMed1992

Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic superior cervical ganglion.

Some characteristics of gamma aminobutyric acid (GABA) uptake and release in rat superior cervical ganglion (SCG) were investigated. Kinetic analysis of GABA uptake indicated the existence of both high affinity (Km = 18.6 microM) and low affinity (Km = 485 microM) uptake systems. 3H-GABA influx was decreased by inhibitors of glial (beta-alanine), neuronal (2,4-diaminobutyric acid, DABA), or glial and neuronal GABA uptake (nipecotic acid). 3H-GABA efflux was elicited by K+ depolarization in a dose-dependent manner, an effect unaltered by severing the preganglionic nerve fibers. Superfusion of SCG explants with DABA or beta-alanine resulted in increased 3H-GABA efflux from tissue, an effect amplified by the absence of calcium in the superfusion medium. 3H-GABA loading in the presence of DABA, but not in the presence of beta-alanine, resulted in abolition of K(+)-elicited 3H release. At 20 mM, but not at 50 mM K+, the release of 3H-GABA was inhibited by replacing Ca2+ by Mg2+ and by adding EGTA, or by incubating SCG in the presence of the Ca(2+)-channel blocker verapamil. Veratrine evoked GABA release in Ca(2+)-independent manner. None of several putative SCG autacoids or agonists (nicotine, muscarine, norepinephrine, dopamine, serotonin, baclofen, muscimol) significantly modified GABA release.

Acetanilides↗

PubMed1992

Time-dependent anesthetic and anticonvulsant activities of alphaxalone in Syrian hamsters.

To assess whether the anesthetic and anticonvulsant activities of alphaxalone display diurnal variability, groups of Syrian hamsters were studied at 4 h-intervals during a 24 h-cycle. The administration of alphaxalone (5 mg/kg) brought about a greater anesthetic activity (loss of righting reflex) at the middle of the photophase. When assessed in hamsters injected with 3-mercaptopropionic acid, alphaxalone displayed maximal anticonvulsant activity at the 4th of darkness. Evaluation of the time needed for first convulsive response indicated that alphaxalone did not show time-dependent effects, while in control hamsters seizure threshold was low during daylight and attained maximal values at night, showing a peak in seizure threshold at light-dark transition.

3-Mercaptopropionic Acid↗

PubMed1992

Light exposure patterns in schizophrenia.

Spontaneous light exposure patterns were studied in 10 chronic schizophrenic patients. Half of our schizophrenic patients exposed themselves to bright light exceeding ordinary indoor illumination. There was a significant positive correlation between the percentage of exposure to bright light and the Brief Psychiatric Rating Scale subscore anergia and a significant negative correlation with depression.

Adult↗

PubMed1992

Binding sites for [3H]-melatonin in human platelets.

A number of in vitro effects of melatonin on human platelets were revealed in previous studies. In order to examine whether high affinity binding sites for [3H]-melatonin were present in membrane preparations of human platelets, a rapid filtration procedure through Whatman GFB paper was employed. Maximal melatonin binding was attained within 3 hr at 0 degree C. Scatchard analysis indicated a single population of binding sites with a dissociation constant (Kd) = 4.1 +/- 0.5 nM and maximal number of binding sites (Bmax) = 24.2 +/- 1.9 fmol/mg protein (mean +/- SEM of five experiments). When various indole analogs were tested for their ability to inhibit [3H]-melatonin binding, the following Ki (nM) were obtained: 6-chloromelatonin (11.4), 2-iodomelatonin (22.0), melatonin (24.7), 5-methoxytryptophol (49.9), N-acetylserotonin (68.9), 6-hydroxymelatonin (78.2), 5-methoxytryptamine (184). Serotonin was a potent inhibitor of [3H]-melatonin binding with a Ki = 20.6 nM. Except for 2-methylserotonin and alpha-methylserotonin, a number of serotonin agonists and antagonists tested did not affect melatonin binding to platelet membranes. Binding experiments carried out at either 0800 or 2000 did not reveal time-dependent differences in Kd or Bmax. The results suggest that high affinity melatonin acceptors are present in human platelets.

Adult↗

PubMed1992

Diurnal changes in cyclic nucleotide response to pineal indoles in murine mammary glands.

The aim of this study was to determine whether pineal indoles affect cyclic nucleotide levels in mammary gland slices of BALB/c adult mice. Melatonin at 0.1 nM-10 microM concentrations decreased cAMP and augmented cGMP concentration in murine mammary gland slices in the presence of a phosphodiesterase inhibitor (1 mM theophylline), an index of cyclic nucleotide synthesis. Melatonin-induced changes in cyclic nucleotide levels were significantly larger at the end of the light period (2000) than in the morning (at 1000). Indole-induced inhibition of cyclic AMP levels by mammary slices exhibited the following order of potency: 5-methoxytryptamine > melatonin > or = 6-hydroxymelatonin > serotonin, N-acetylserotonin > 5-hydroxytryptophol. The order of potency for indole-induced augmentation of cyclic GMP levels was: 5-methoxytryptamine > melatonin > 6-hydroxymelatonin > serotonin, N-acetylserotonin, 5-hydroxytryptophol. When melatonin or 5-methoxytryptamine (10 nM) were examined for their effects on cAMP and cGMP levels in mammary glands of mice killed at six different time intervals during the 24-hr cycle, the activity was maximal during night. The data demonstrate that 5-methoxytryptamine and melatonin decreased cAMP and increased cGMP levels in mammary gland slices. Methoxyindole-induced changes in cyclic nucleotide synthesis in murine mammary glands exhibit the time-dependency known to occur in several other melatonin-influenced responses.

Animals↗

PubMed1992

Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism.

We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical actometer, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scotophase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist flumazenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing gamma-aminobutyric acid (GABA) as an inhibitory transmitter.

Animals↗

PubMed1992

Effect of zeitgeber intensity reduction on a simulated dual-oscillator human circadian system: classical and dynamic analysis.

The two-oscillator model of human circadian rhythmicity was analyzed when a zeitgeber relative intensity of 1, 0.5, or 0.1 was introduced into the equations. Fourier analysis was compared with dynamic analysis such as attractor reconstruction or Liapunov exponent calculation. After a 50 or 90% reduction in zeitgeber intensity, the dynamics of the system became equivalent and differed significantly from those of a system with maximal zeitgeber intensity. When 10% aleatory noise was added to the data, the analysis was still applicable, and the results obtained were essentially the same as in the absence of noise. Dynamic analysis could thus provide a distinct classification for periodic data, based on the type of analysis.

Biometry↗

PubMed1992

Time-dependency for the effect of different stressors on rat pineal melatonin content.

This study describes the effects of two stressors, swimming for 15 min or i.p. beta-carboline (beta-CCE) injection, on rat pineal melatonin levels when applied either at the end of the light period of daily photoperiod (1800 h) or at the expected melatonin maximum (at 2200 h). Neither procedure affected melatonin levels at 1800 h. In contrast, both stressors were effective to augment pineal melatonin content when applied at 2200 h. When applied at light-dark transition, only beta-CCE injection increased pineal melatonin levels at the middle of the night. Neither procedure was effective to counteract the inhibition of pineal melatonin content caused by prolonging the light phase for 4 h. Deprivation for two days of water, but not of food, augmented pineal melatonin levels in rats killed at the end of the light period, up to levels that were undistinguishable from those found at 2200 h. No differences were found between the two stressors and controls when tested at 2200 h. The present results further support the concept that stressful stimuli can influence differentially pineal melatonin production.

Animals↗

PubMed1992

Some neurovegetative correlates of Minnesota Multiphasic Personality Inventory (MMPI)

In 57 patients with psicovegetative disorders and abnormal MMPI, abnormality in MMPI scales indicating hypochondriasis, hysteria, gender deviant, paranoia, psychastenia, schizophrenia, hypomania or introversion was accompanied by increased plasma catecholamine levels and/or responses to hypoglycemia or by an increased cardiovascular reactivity. A high depression scale was associated with lower plasma catecholamine levels. Blunted plasma growth hormone responses to hypoglycemia were found in abnormal hypomania scale, and augmented responses of plasma cortisol in abnormal hysteria or schizophrenia scales. Paranoia and hypomania traits correlated with absence of morning-evening differences in blood cortisol levels. Electrodermal responses compatible with increased sympathetic activity correlated with high hysteria, gender, paranoia, schizophrenia or hypomania MMPI scales. This study indicates that most psychopathological traits in MMPI are accompanied by humoral and/or electrophysiological signs of abnormality of the autonomic nervous system.

Adolescent↗

PubMed1991

Effect of cyclosporine on ornithine decarboxylase activity in rat submaxillary lymph nodes: modulation by sympathetic nerves.

In order to examine whether cyclosporine activity in submaxillary lymph nodes is dependent on sympathetic modulation, rats received a unilateral superior cervical ganglionectomy together with a contralateral sham-operation. Two weeks later, cyclosporine (5 or 20 mg/kg per day s.c.) was injected for five days. Freund's complete adjuvant was injected 1 h before the third injection of cyclosporine and the rats were killed 2 h after the last injection of cyclosporine. A significant increase in ornithine decarboxylase activity in submaxillary lymph nodes was observed two weeks after sympathetic denervation. Cyclosporine decreased enzyme activity in submaxillary lymph nodes on the sham-operated side by 67-77% and by 21-41% on the denervated side (P less than 0.01). The incorporation of [35S]methionine into proteins in ipsilateral submaxillary lymph nodes was increased by unilateral superior cervical ganglionectomy and decreased by cyclosporine to a similar extent in denervated and innervated lymph nodes. Superior cervical ganglionectomy decreased by about 93-95% the norepinephrine content of submaxillary lymph nodes regardless of cyclosporine treatment. The results indicate that an appropriate sympathetic neural environment is needed for cyclosporine to have an effect on ornithine decarboxylase activity in lymphoid tissue.

Animals↗

PubMed1991

Time-dependent melatonin analgesia in mice: inhibition by opiate or benzodiazepine antagonism.

The aim of this study was to determine whether melatonin-induced analgesia in mice exhibits the time dependency known to occur for several other effects of the hormone, and to analyze to what extent the activity of melatonin can be inhibited by the opiate antagonist naloxone or the central-type benzodiazepine (BZP) antagonist Ro 15-1788. Analgesia was assessed with the hot plate procedure. There was a significant diurnal variation in the pain threshold, with an increase in latency during the dark phase of the daily photo period. Melatonin (20-40 mg/kg i.p.) exhibited maximal analgesic effects at late evening (20:00 h). The administration of naloxone or Ro 15-1788 at 20:00 h, although unable by themselves to modify pain threshold, blunted the analgesic response to melatonin. Significant increases in the latency of the hot plate response were found after diazepam injection, an effect blocked by Ro 15-1788 or naloxone. These results indicate that time-dependent melatonin analgesia is sensitive to opioid or central-type BZP antagonism.

Analgesics↗

PubMed1991

Hypothalamic luteinizing hormone-releasing hormone content and serum luteinizing hormone levels in male rats during wallerian degeneration of sympathetic nerve terminals after superior cervical ganglionectomy.

The main hypothesis of this study was that sympathetic neurons located at the superior cervical ganglia (SCG) control luteinizing hormone (LH) releasing mechanisms by acting at a hypothalamic site. To test this, medial basal hypothalamus (MBH) luteinizing hormone-releasing hormone (LHRH) content and serum LH levels were measured in male rats subjected to superior cervical ganglionectomy (SCGx) or sham-operation 14 or 38 h earlier, at the time of degeneration of nerve endings post-SCGx. Significantly augmented MBH LHRH levels and decreased circulating LH were found in SCGx rats. In animals subjected to SCGx 14 h earlier and receiving a single injection of the alpha 1-adrenergic blocker prazosin, the beta-adrenergic blocker propranolol or a mixture of both drugs 45 min before sacrifice, only the injection of prazosin prevented the decrease of plasma LH levels. Neither treatment prevented the increase in MBH LHRH content. When prazosin was given every hour starting from the 10th to the 13th h after surgery, it was effective to prevent both the increase of MBH LHRH content and the decrease of serum LH found during sympathetic nerve degeneration. Similar repetitive injections of propranolol resulted in the greatest depression of serum LH, and in the greatest increase of MBH LHRH observed. Serum LH response to LHRH injection was similar in SCGx and sham-operated rats. The data indicate that SCG neurons exert, through inhibitory alpha 1-, and weaker, stimulatory beta-adrenoceptors, a significant influence on LHRH release at a supra-hypophysial site.

Animals↗

PubMed1991

Time-dependency for the bimodal effect of melatonin on calcium uptake in rat hypothalamus. Short communication.

The activity of 0.01-1 microM of melatonin on depolarization-induced 45Ca2+ influx by hypothalamic synaptosomes of rats killed at late evening (2000 h) depended on melatonin preincubation time, exhibiting an early (10 min) stimulation of uptake and an inhibition after 30 min of incubation. Both stimulatory and inhibitory effects were maximal at 2000 h and tended to a minimum at 2400 h, exhibiting intermediate values at 400 h. At 1000 h, only inhibitory effects of melatonin (1 microM) on Ca2+ uptake were found.

Animals↗

PubMed1991

Compensatory parathyroid hypertrophy after hemiparathyroidectomy in rats feeding a low calcium diet.

The functional and anatomic compensatory response of the parathyroid gland was examined in hemiparathyroidectomized (HPTx) rats whose parathyroid hormone (PTH) secretion was stimulated by a low calcium diet. These responses were compared with those observed in the thyroid gland of hemithyroidectomized (HTx) rats. Rats kept on a low calcium diet for 10 days were subjected to HPTx, HTx, or sham operations. Throughout the experiment (up to 28 days after surgery), serum calcium levels of HPTx rats were lower than the basal, with delta values (mg/dl, mean +/- SEM) of -0.66 +/- 0.17 and -0.84 +/- 0.17, (P less than 0.05) 3 and 28 days after surgery, respectively. Serum PTH decreased significantly from 7 to 21 days after HPTx, reaching normality at day 28 after surgery. In HTx rats, serum thyroxine (T4) levels diminished significantly 7 days after surgery, and attained normality thereafter. The mitotic index (number of metaphases/1,000 cells) in parathyroid glands of colchicine-treated HPTx rats increased significantly in comparison to sham-operated controls, when examined 2 or 40 days after surgery. The mitotic index of thyroid follicular cells was significantly higher than that of their respective controls, 2 but not 40 days after HTx. These results indicate that after HPTx, a delayed compensatory response is found when the animals are kept under a low calcium diet. Parathyroid response is both delayed and of a minor degree compared to that found in the thyroid gland after HTx.

Adaptation, Physiological↗

PubMed1991

Melatonin-induced depression of locomotor activity in hamsters: time-dependency and inhibition by the central-type benzodiazepine antagonist Ro 15-1788.

The aim of the present study was to determine whether melatonin-induced depression of locomotor activity in hamsters is time-dependent and to analyze the inhibitory effects of the central-type benzodiazepine (BZP) antagonist Ro 15-1788 on melatonin-induced depression of locomotor behavior. Activity was monitored and registered by means of an optical actometer. Two phases of locomotor behavior were found. The initial phase, found both at noon and during the evening, exhibited an absence of diurnal variability, while a second long-lasting phase of activity exhibited a peak at early night. The IP injection of melatonin (minimal effective dose: 100 micrograms/kg) inhibited the early phase of activity at 1200 or 2000 h. Inhibition of the late phase of activity was found at 2000 or 0400 h, but not at midnight. When assessed at 2000 h, melatonin depression of the early phase of locomotor activity attained significance after 5 days of injection, while its effect on the late phase of activity attained significance during the second day of injection. The administration of Ro 15-1788, although unable by itself to modify locomotor activity, significantly attenuated the inhibitory effects of melatonin. These results indicate the existence of a time-dependency for melatonin activity on locomotor behavior similar to that known to occur for other effects of the hormone, and further support a link between melatonin and the activity of central type BZP receptors.

Animals↗

PubMed1991

Slower growth of tumours in sympathetically denervated murine skin.

In order to examine tumour growth in sympathetically denervated murine skin, two breast cancer tumour lines were employed, i.e. M3 tumours, of a relatively high local growth and low metastatic capacity, and MM3-LN tumours, that grew locally at a slower rate but disseminated early to the lung. Mice subjected to unilateral superior cervical ganglionectomy or sham-operation 2 weeks earlier were used. M3 or MM3-LN tumours were implanted in the ipsilateral ear to the surgical procedure. Tumour size was assessed every 2-6 days, starting from the 7th day after tumour implantation. Growth of M3 and MM3-LN tumours was significantly slowed by a previous sympathetic denervation of the skin territory. There were no significant differences in the number or size of pulmonary metastases at autopsy between mice subjected to ganglionectomy or to sham-operation. Ganglionectomy increased significantly ipsilateral submaxillary lymph node ornithine decarboxylase activity by 62% and decreased noradrenaline content to 8% of the innervated contralateral lymph node. The present results indicate a local inhibitory modulation of tumour growth by the sympathetic nervous system.

Adenocarcinoma↗

PubMed1991

Presynaptic effects of melatonin on norepinephrine release and uptake in rat pineal gland.

The effect of melatonin injection on norepinephrine (NE) turnover rate in rat pineal gland was estimated from the decline of tissue NE levels after the injection of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine. The administration of a single injection of 300 micrograms/Kg of melatonin at the beginning of the scotophase induced, 3 hr later, a significant decrease of pineal NE turnover. The possible direct effect of melatonin on pineal NE release was examined in vitro. Exposure of rat pineal explants previously loaded with 3H-NE to 10(-8)-10(-6) M melatonin decreased significantly 3H-NE release triggered by 60 mM K+. This activity of melatonin was revealed only in pineals excised at night (0000 and 0400, i.e., at the fourth or eighth hours of darkness) and not in those excised in the middle (1400) or late light phase of the daily photoperiod (2000). Melatonin did not modify the spontaneous pineal 3H-NE efflux. Melatonin decreased 3H-NE uptake at a low NE concentration (0.5 microM) in a dose-dependent manner (IC50 identical to 10(-10) M). A kinetic analysis of the pineal NE uptake process indicated that melatonin augmented both Vmax and Km of transmitter uptake. These results suggest that endogenously released melatonin may be a regulatory signal for rat pineal sympathetic synapses.

Analysis of Variance↗