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Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Evidence suggesting that the sympathetic nervous system mediates thyroidal depression in turpentine-induced nonthyroidal illness syndrome.

Acute superior cervical ganglionectomy (SCGx) induces in the rat a supraliminal release of neurotransmitter in the innervated tissues (i.e., thyroid gland). This temporary adrenergic hyperactivity is correlated with a significant depression of the thyroid economy resembling the nonthyroidal illness (NTI) syndrome in the rat, and suggest that the sympathetic nervous system may mediate thyroidal changes in NTI. In order to gain further insight into the thyroidal depression in the NTI syndrome, we studied the thyroidal norepinephrine (NE) turnover in turpentine oil (TURP)-induced NTI syndrome and the role of the cervical ganglia (SCG) in the development of NTI in the rat. TURP administration to sham operated rats induced a rapid and significant fall in plasma T4 and TSH levels, in the thyroidal response to exogenous TSH (TIU) and in the thyroidal NE content compared to controls (sham + saline) (T4: 3.1 +/- 0.3 vs. 5.1 +/- 0.6 micrograms/dl, respectively, mean +/- SE, p less than 0.02; TSH: 1.4 +/- 0.4 vs. 4.7 +/- 1.4 ng/ml, respectively, p less than 0.05; TIU: 92 +/- 14 vs. 201 +/- 20 cpm.microliter thyroid/cpm.mg plasma (T/P ratio), respectively, p less than 0.01; thyroidal NE: 680 +/- 20 vs. 761 +/- 29 pg/mg thyroid, respectively, p less than 0.05). The thyroidal turnover rate of NE, however, was significantly increased in TURP-injected rats compared to controls (122 +/- 13 vs. 86 +/- 10 pg/mg/h, respectively, p less than 0.05). TURP injection to chronic SCGx rats induced a similar fall in plasma TSH compared to controls (SCGx + saline) (1.3 +/- 0.2 vs. 4.3 +/- 1.1 ng/ml, respectively, p less than 0.02); plasma T4 and TIU, however, did not change significantly (T4: 3.4 +/- 0.4 vs. 3.7 +/- 0.3 micrograms/dl, respectively, NS; TIU: 172 +/- 8 vs. 226 +/- 27 T/P ratio, respectively, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anterograde nerve degeneration after superior cervical ganglionectomy coexists with a decrease in arginine vasopressin release in rats.

After bilateral superior cervical ganglionectomy (SCGx) in adult male rats, norepinephrine content of the pituitary neurointermediate lobe (NIL) decreased at 12-24 h after surgery to attain concentrations 40-60% of controls between 24 and 60 h after surgery. To assess arginine vasopressin (AVP) secretion during this time, plasma and NIL-AVP levels were measured by radioimmunoassay. In sham SCGx controls, plasma AVP increased about 2-fold within 6 h after surgery and decreased thereafter, to attain presurgical values by 60 h after surgery. In SCGx rats, a significant increase in plasma AVP concentration was observed at the 6th h after surgery, as compared to presurgical concentrations, with a decrease to values significantly lower than those of presurgical controls at 16-18 h after SCGx. As compared to sham-operated rats, significantly higher plasma AVP levels 6 h after surgery and significantly lower plasma AVP levels 16-24 h after surgery were found. NIL-AVP concentration in SCGx and sham-operated ras were significantly lower than presurgical levels at 6 h after surgery. SCGx rats had significantly higher amounts of AVP in NIL at 16-24 h after surgery. The changes in plasma and NIL-AVP levels found 6 or 16 h after SCGx or sham SCGx were unaffected by a prior pinealectomy. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta-blocker propranolol, prevented the increase in plasma AVP found in SCGx rats 6 h after surgery, and the decrease in plasma AVP and the increase of NIL-AVP found 16 h after SCGx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro effect of thyroxine on cholinergic neurotransmission in rat sympathetic superior cervical ganglion.

This study aimed at examining the effect of thyroid hormones on cholinergic transmission in isolated rat superior cervical ganglia (SCG). In SCG explants incubated with 3H-choline, thyroxine (T4) and 3,3',5-triiodothyronine (T3) added to the medium before a second depolarization stimulus of 60 mM K+ resulted in a dose-dependent increase of S2/S1 ratio for 3H release. The concentration of hormone that produced 50% of maximal increase in K(+)-induced radioactivity release was 8 x 10(-9) M for T4 and 1.6 x 10(-8) M for T3 while 3,3',5,5'-tetraiodothyroacetic acid was almost ineffective. Preincubation of SCG with 10(-7) M iopanoic acid for 30 min before S2, although not affecting by itself S2/S1 ratio, effectively prevented the increase given by T4 or T3. 3H-acetylcholine release by SCG was augmented in a high K+, and the effect was amplified by T4 to a similar extent as that for total 3H release. When added to the incubation medium together with 60 mM K+ for 30 min, T4 (10(-7) M) increased significantly the activity of choline acetyltransferase (ChAT). T4 did not affect ChAT activity in SCG exposed to 4.7 mM K+, nor in SCG homogenates. 3H-choline uptake measured immediately after exposure of SCG to 60 mM K+ decreased by 25%, whereas it increased by 71% after a subsequent 30-min incubation with 4.7 mM K+. Addition of 10(-7) M T4 prevented the changes in choline uptake observed in a high K+ medium. These results indicate that T4 increases SCG cholinergic transmission.

Animals↗

Effect of a melatonin implant on the circadian variation of plasma prolactin and rectal temperature in newborn sheep.

Plasma prolactin and rectal temperature show a circadian rhythm in newborn sheep raised under continuous light. Melatonin lowers the concentration of plasma prolactin but it is not known if it affects its circadian rhythm. To detect whether melatonin acts on the circadian system we studied the effect of a subcutaneous melatonin implant in the circadian rhythms of prolactin and rectal temperature in newborn lambs raised under continuous light. We placed catheters in the pedal artery and vein in 9 newborn lambs (2-5 days of age). A subcutaneous melatonin implant was placed in 4 of the lambs at 9-12 days of age. Blood samples and rectal temperature measurements were obtained hourly for a period of 24 h, 11-15 days after the implant, at 20-27 days of age. To avoid interferences of heparin in our melatonin assay, serum melatonin concentration was measured before and during the implant in three additional newborns. Prolactin and melatonin were measured by RIA. Melatonin concentrations were 52.8 +/- 45.9 pg/ml (day) and 315.5 +/- 77.0 pg/ml (night) before treatment (SEM, P less than 0.001), and increased to 594.1 +/- 54.5 pg/ml after placing the implant (there was no difference in melatonin concentration between day and night during the time that the implant was in place). Melatonin had no effect on rectal temperature or its rhythm, but decreased basal plasma prolactin concentration (control: 97.5 +/- 11.3 ng/ml; treated: 25.1 +/- 2.4 ng/ml, P less than 0.001) and abolished the prolactin circadian rhythm, (Cosinor analysis): control: log prolactin (ng/ml) = 1.8 + 0.26 cos 15 (t - 11.16), p = 0.05; treated: log prolactin (ng/ml) = 1.2 + 0.14 cos 15 (t - 9.43), P = 0.36.

Animals↗

Autonomic peripheral evoked potential (APEP): a non-invasive procedure to assess sympathetic responses in humans.

The present study describes skin potential responses during a sequence of extero-, intero- and proprioceptive stimuli in 73 normal human subjects. By plotting the first derivative of skin potential vs. skin potential changes for every stimulus (phase plane) a generally opposite behavior of positive and negative deflections (indicating sympathetic inhibition and activation, respectively) was found. By area subtraction in phase plane analysis, only olfactory stimulation or nasal hyperventilation exhibited a significantly negative (sympathetic activating) skin potential response. Frequency of positive (sympathetic inhibitory) fluctuations of first derivative of skin potential was significantly lower than basal after explosive sound, tactile discrimination, photomotor reflex, and nasal and oral hyperventilation. Frequency of negative (sympathetic activating) fluctuations augmented significantly (as compared to basal) after explosive sound, tactile discrimination, nasal or oral hyperventilation, upright position or trot. These results suggest that activation of the sympathetic nervous system involves a coordinated motor program comprising activation of certain areas, and inhibition (or lack of changes) in others, with different patterns of interrelated activation and inhibition depending upon stimulus.

Adolescent↗

Diurnal changes in actin mRNA levels and incorporation of 35S-methionine into actin in the rat hypothalamus.

1. The in vitro incorporation of 35S-methionine into actin and total soluble proteins, as well as the levels of actin mRNA, were studied in the hypothalamus and frontal cerebral cortex of adult male rats killed at six different time intervals during a 24-hr cycle. 2. The specific activity of total soluble proteins after labeled methionine incubations did not vary as a function of time of day in any of the examined brain regions. 3. The incorporation of 35S-methionine into a 43-kDa protein, corresponding to the electrophoretic mobility of actin, varied diurnally in the hypothalamus, exhibiting a maximum at 1200 hr. Such a diurnal variation was not found in frontal cerebral cortex. 4. Similar results were obtained when labeled methionine incorporation into actin was assessed in hypothalamus and cerebral cortex by an immunoprecipitation procedure. 5. An increase in actin hypothalamic mRNA levels, quantitated by dot-blot analysis, was found at 0800, 4 hr in advance to the maximum in 35S-methionine incorporation to actin. 6. The levels of actin mRNA did not vary significantly as a function of time of day in the frontal cerebral cortex.

Actins↗

Presynaptic effects of gamma-aminobutyric acid on norepinephrine release and uptake in rat pineal gland.

The effect of tau-aminobutyric acid (GABA) on pineal norepinephrine (NE) release was examined in vitro in the rat pineal gland. Exposure of pineal explants previously loaded with 3H-NE to 1-100 microM GABA caused a dose-dependent decrease of 3H-NE release triggered by 60 mM K+, with a threshold GABA concentration of 1 microM and IC50 of about 10 microM. The inhibitory effect of GABA was mimicked by the type B GABA agonist baclofen, displaying a similar dose-response relationship as GABA. The type A GABA agonist muscimol increased depolarization-induced 3H-NE release, while the co-incubation with GABA and the type A receptor antagonist bicuculline augmented significantly GABA's depressive effect on 3H-NE release. Bicuculline alone brought about a significant decrease of 3H-NE release. Neither GABA, nor baclofen, muscimol or bicuculline, modified the spontaneous pineal 3H-NE efflux. Assessment of 3H-NE uptake at a low NE concentration (0.5 microM) indicated that GABA decreased it in a dose-dependent manner (IC50 = 100 microM) through an effect blocked by bicuculline and mimicked by muscimol but not by baclofen; at a 5 microM-3H-NE concentration a bicuculline-sensitive GABA augmentation of uptake was found. A kinetic analysis study of the pineal NE uptake process indicated that GABA augmented both Vmax and Km of transmitter uptake. These results indicate that GABA may be a significant regulatory signal for rat pineal sympathetic synapses.

Animals↗