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L Kapás

Publications and source records attributed to L Kapás.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of systemic GHRH on sleep in intact and hypophysectomized rats.

The role of pituitary growth hormone (GH) in the mediation of enhanced sleep elicited by GH-releasing hormone (GHRH) was studied in the rat. Intact and hypophysectomized (HYPOX) rats received systemic injections of GHRH or physiological saline. GHRH (0.5, 5.0, or 50 micrograms/kg in the intact rats and 0.5 or 50 micrograms/kg in HYPOX rats) was injected 6 h after light onset (P.M. injection) or just before light onset (A.M. injection, 0.5 microgram/kg in both A.M. groups). Sleep-wake activity and brain cortical temperature were recorded for 23 h (12 h light + 11 h dark). A.M. injection of GHRH did not alter sleep in normal or HYPOX rats. Each dose of P.M. GHRH increased rapid-eye-movement sleep (REMS) during 6 h postinjection in the intact rats. Hypophysectomy abolished the REMS-promoting activity of GHRH. P.M. injection of 0.5 microgram/kg GHRH increased non-REM sleep (NREMS) and enhanced electroencephalogram slow-wave activity during NREMS in both the intact and the HYPOX rats. The NREMS-promoting activity disappeared when the dose of GHRH was increased in the intact rats, whereas a tendency to enhanced NREMS was still observed after 50 micrograms/kg GHRH in the HYPOX rats. GHRH stimulated GH secretion dose dependently in the intact rats. A.M. injection of 0.5 microgram/kg GHRH tended to be less effective in stimulating GH release than the same dose administered P.M. The results confirm the time-of-day variations in the GHRH effects on sleep previously reported in human subjects. It is likely that pituitary GH is involved in the mediation of the REMS-promoting activity of GHRH but not in the NREMS-promoting activity of GHRH. Nevertheless, the results do not exclude the possibility that GH may modulate NREMS.

Animals↗
PubMed1996

An interleukin-1 receptor fragment inhibits spontaneous sleep and muramyl dipeptide-induced sleep in rabbits.

Interleukin-1 (IL-1) is hypothesized to be involved in physiological sleep regulation and in sleep responses occurring during infectious disease. If this hypothesis is correct, then inhibition of endogenous IL-1 should reduce both normal sleep and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-induced sleep. MDP is a somnogenic substance derived from bacterial cell walls. We report here the effects of a synthetic IL-1 receptor fragment corresponding to amino acid residues 86-95 of the human type I IL-1 receptor (IL-1RF) on spontaneous sleep and IL-1 beta- and MDP-induced sleep and fever in rabbits. Two doses of the IL-1RF (25 and 50 micrograms) were injected into normal rabbits intracerebroventricularly (icv). Both doses significantly decreased spontaneous non-rapid eye movement sleep (NREMS) across a 22-h recording period. Pretreatment of rabbits with 25 micrograms of IL-1RF blocked the somnogenic actions of 10 ng icv IL-1. Similarly, central pretreatment of animals with 25 micrograms IL-1RF significantly attenuated the NREMS-promoting and REMS-suppressive actions of 150 pmol MDP injected centrally. The increase in NREMS and decrease in REMS induced by systemic injection of 12.5 micrograms/kg MDP were also significantly suppressed by central administration of 50 micrograms IL-1RF. In contrast, the febrile response induced by either intracerebroventricularly or intravenously injected MDP were not significantly affected by IL-1RF. These results support the hypothesis that endogenous, brain-derived IL-1 contributes to the maintenance of normal sleep and may mediate sleep responses to systemic as well as central bacterial infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds.

Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial products, such as muramyl peptides, via their ability to enhance cytokine production. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia also had this capacity. Primary cultures of microglia were allowed to phagocytize and digest Staphylococcus aureus radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight substances released into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature after intracerebroventricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamental macrophage functions and further implicate microglia as resident immunocompetent cells.

Animals↗
PubMed1995

An anti-tumor necrosis factor antibody suppresses sleep in rats and rabbits.

It is hypothesized that tumor necrosis factor (TNF) is an endogenous sleep-promoting substance. In the present experiments we studied the effects of a monoclonal anti-TNF antibody in rats and rabbits. Seven rats and 14 rabbits were implanted with electroencephalographic electrodes, a brain thermistor and an intracerebroventricular guide cannula. The animals were injected with saline, control IgG, and monoclonal hamster anti-murine-TNF antibodies (TNFab) on 3 separate days. Ten micrograms TNFab suppressed non-rapid-eye-movement sleep (NREMS) in rats. In rabbits, 2.5 micrograms TNFab did not affect sleep but decreased brain temperature; in contrast, 25 micrograms TNFab suppressed NREMS without affecting brain temperature. These results are consistent with the hypothesis that endogenous TNF plays an important role in sleep regulation.

Analysis of Variance↗
PubMed1995

Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep.

Tumor necrosis factor (TNF) is a cytokine that possesses many biological activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF is involved in sleep regulation, then reduction of endogenous TNF should suppress spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic fragment of TNF-BP I, TNF-R-(159-178), that contains the biologically active region of TNF-BP I, were used. These substances bind TNF and possess TNF-inhibitory activity; their effects on rabbit sleep after intracerebroventricular injection were determined across a 6-h recording period. Two doses of TNF-BP I (0.05 micrograms and 0.5 micrograms) were administered; the higher dose of TNF-BP I significantly decreased NREMS. Four doses of TNF-R-(159-178) (0.25 micrograms, 2.5 micrograms, 25 micrograms and 50 micrograms) were used. The 25 micrograms and 50 micrograms doses significantly suppressed NREMS. The highest dose (50 micrograms) also decreased REM sleep. These results are consistent with the hypothesis that endogenous brain TNF is involved in the regulation of normal sleep.

Animals↗
PubMed1995

Cytokines in sleep regulation.

The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process results from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects neurons and glia. Evidence in support of these postulates is reviewed in this essay.

Acute-Phase Reaction↗
PubMed1995

Acidic fibroblast growth factor (FGF) but not basic FGF induces sleep and fever in rabbits.

Acidic fibroblast growth factor (FGF) and basic FGF belong to a growth factor family. Interleukin-1, another member of that family, is involved in sleep regulation. FGFs and interleukin-1 share structural and functional features. We therefore determined whether acidic FGF and basic FGF were somnogenic. Male New Zealand White rabbits were provided with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular (icv) cannula. The animals were injected icv with isotonic NaCl (control) and on separate days with one of three doses of acidic or basic FGF (0.01, 0.1, or 1.0 micrograms) or with heat-treated acidic FGF (1.0 micrograms). The EEG, brain temperature, and motor activity were recorded for 23 h. The biological activity of basic FGF was determined in vitro by its ability to induce DNA synthesis in rat aortic smooth muscle cells. Acidic FGF induced prolonged dose-related increases in non-rapid eye movement sleep beginning in the 1st postinjection h and continuing for 12-23 h after the treatment. Acidic FGF also induced fevers of approximately 1 degree C after the 1.0 micrograms dose. Both activities of acidic FGF were lost after heat treatment. In contrast, basic FGF lacked somnogenic and pyrogenic activity, although it did induce DNA synthesis. Current results suggest that acidic FGF is part of the complex cytokine network in brain involved in sleep regulation.

Animals↗
PubMed1994

Inhibition of nitric oxide synthesis inhibits rat sleep.

Previous findings indicate that nitric oxide (NO) may play a role in the regulation of sleep-wake activity. In rabbits, blocking the production of endogenous NO by a nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NAME) suppresses spontaneous sleep and interferes the somnogenic actions of interleukin 1. In the present experiments we extended our earlier work by studying the long-term effects of L-NAME treatment on sleep-wake activity including power spectra analyses of the electroencephalogram (EEG) in rats. Rats implanted with EEG electrodes, brain thermistor, and intracerebroventricular (i.c.v.) guide cannula were injected i.c.v. with vehicle or 0.2, 1, or 5 mg L-NAME at light onset. In separate experiments, rats were injected intraperitoneally (i.p.) with L-NAME three times (50, 50, 100 mg/kg), 12-12 h apart. Both i.c.v. and i.p. injections of L-NAME elicited decreases in time spent in NREMS and REMS. After i.c.v. injection of 5 mg L-NAME the sleep responses were long-lasting; NREMS did not return to baseline even 72 h after injection. EEG delta-wave activity during NREMS (slow wave activity) was also suppressed after 0.2 and 5 mg L-NAME. Brain temperature was slightly increased after the two lower doses of L-NAME, whereas there was a transient decrease in Tbr after 5 mg L-NAME. Acute i.p. injection of 50 mg/kg L-NAME elicited an immediate decrease in NREMS which lasted for approximately 2 h. The second injection of 50 mg/kg L-NAME and the following injection of 100 mg/kg L-NAME induced biphasic decreases in NREMS but not REMS.

Amino Acid Oxidoreductases↗
PubMed1994

Involvement of prolactin in the REM sleep-promoting activity of systemic vasoactive intestinal peptide (VIP).

The involvement of pituitary prolactin (PRL) in systemic vasoactive intestinal peptide (VIP)-induced sleep was studied. Male rats were implanted with electrodes for EEG-recording, with brain thermistors to record cortical temperature (Tcrt) and with chronic intracardial catheters to obtain blood samples and to deliver substances. One group of rats (n = 8) received normal rabbit serum (NS)+physiological saline (SAL) on the baseline day and was injected with NS+VIP on the experimental day. In the other group of rats (n = 6), the baseline day was followed by administration of PRL-antiserum (PRL-AS) + VIP on the experimental day. The sera and VIP or SAL were injected 30 min before and at light onset, respectively. Sleep-wake activity was then recorded for the next 12-h light period. Systemic VIP-stimulated PRL secretion as measured by RIA in serial samples obtained hour 1 postinjection. VIP also elicited selective increases in REM sleep (REMS) in the rats pretreated with NS. Tcrt was not affected by VIP. Administration of PRL-AS blocked the increase in circulating levels of free (non-IgG-bound) PRL and prevented VIP-enhanced REMS. Comparisons of the sleep effects of PRL-AS+VIP with the previously reported changes in sleep after PRL-AS alone indicate that PRL has a major role in the mediation of the REMS-promoting activity of systemic VIP. The results suggest that an increased release of endogenous pituitary PRL modulates REMS.

Animals↗
PubMed1994

Somnogenic activity of muramyl peptide-derived immune adjuvants.

Muramyl peptides (MPs) possess immunostimulatory, pyrogenic and somnogenic activities. The structural requirements of MPs for each of these activities are different though certain MPs, e.g. muramyl dipeptide (NAM-L-ala-D-isogln) possess all three activities. Several MPs are proposed for use as immune adjuvants; somnogenic and pyrogenic activities would be considered adverse side effects of such compounds. We report here that some of the putative adjuvants, GIF101, WG209 and MDP-threonine lack somnogenic and pyrogenic activities. Current results also expand our understanding of the structural requirements for these activities. Major findings are that the addition of the dipeptide L-ala-D-isogln to NAG-NAM-L-ala-D-isogln blocks the activity of the latter compound and that the amino sugar moiety of MPs, NAM, is unnecessary for somnogenic and pyrogenic activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Inhibition of nitric oxide synthesis suppresses sleep in rabbits.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, on spontaneous and interleukin-1 (IL-1)-induced sleep were examined in rabbits. Animals were injected intracerebroventricularly or intravenously during the light phase with vehicle, L-NAME, IL-1, or the combination of L-NAME and IL-1. Injection of L-NAME (5 mg icv and 100 mg/kg iv) suppressed both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) for 4-6 h. The sleep-suppressive effects are unlikely due to pressor responses to L-NAME because administration of L-NAME (5 mg icv) produced only a transient (3-4 min) slight increase in systemic blood pressure. Injection of IL-1 (20 ng icv) elicited fever, suppressed REMS, and increased NREMS for 6 h. NREMS was suppressed for 3 h after the combined intracerebroventricular injections of 5 mg L-NAME and 20 ng IL-1 and was elevated during postinjection hours 4-6. Administration of IL-1 (30 ng/kg iv) increased NREMS and brain temperature for 2 h. After the combined injection of IL-1 and L-NAME (100 mg/kg), NREMS was significantly suppressed during postinjection hours 1-5. It is not known whether the interactions between the sleep-suppressive effects of L-NAME and the NREMS-promoting effects of IL-1 are specific, being mediated via a common mechanism, or whether they are additive, being mediated via independent mechanisms. The pyrogenic and REMS-suppressive actions of either intracerebroventricularly or intravenously injected IL-1 were not affected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Prostaglandins E2 and D2 have little effect on rabbit sleep.

Prostaglandins (PGs) are hypothesized to be involved in sleep regulation; PGE2 and PGD2 are major PGs in the hypothalamus of many species and are proposed to reciprocally promote wakefulness and sleep respectively. PGD2 and PGE2 are also major PGs in rabbit cerebrospinal fluid, yet their effects on rabbit sleep have not heretofore been systematically investigated. We report here that a bolus injection of PGE2 into a lateral cerebral ventricle induces dose-dependent fevers and transient sleep responses in rabbits. PGE2 induces a suppression of sleep of 24 min duration. In contrast, PGD2, across a wide range of doses (0.25-500 nmol) failed to alter sleep; however, at the highest dose it induced fever. We conclude that if PGs are involved in sleep regulation, a chronic stimulation of their production by other sleep factors is necessary.

Animals↗
PubMed1992

Tumor necrosis factor-beta induces sleep, fever, and anorexia.

The enhanced sleep, fever, and anorexia experienced during general infections are attributed to the increased production of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have characteristic somnogenic, pyrogenic, and anorectic effects. TNF-beta is closely related to TNF-alpha, and they share common receptors. The effects of TNF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were, however, heretofore unknown. We injected 0.5-200 ng TNF-beta into rabbits intracerebroventricularly (icv) in the light period, and the electroencephalogram, movement, and Tbr were recorded for 6 h from rabbits. The highest dose, 200 ng TNF-beta, induced increases in non-rapid-eye-movement sleep and decreases in rapid-eye-movement sleep accompanied with biphasic febrile responses. Icv injection of 100 ng TNF-beta at dark onset suppressed 12-h and 24-h food intake in rats. These data suggest to us that TNF-beta may belong to the group of endogenous pyrogens/sleep factors.

Animals↗
PubMed1992

Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments.

Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.

Animals↗
PubMed1992

Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation.

Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (Tbr), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 micrograms) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and Tbr were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 micrograms) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and Tbr of rats were recorded for 24 h in three experimental conditions: base-line with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 micrograms). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat.

To study the possible involvement of hypothalamic growth hormone-releasing factor (GRF) in sleep regulation, a competitive GRF-antagonist, the peptide (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2, was intracerebroventricularly injected into rats (0.003, 0.3, and 14 nmol), and the EEG and brain temperature were recorded for 12 h during the light cycle of the day. Growth hormone (GH) concentrations were determined from plasma samples taken at 20-min intervals for 3 h after 14 nmol GRF-antagonist. The onset of non-rapid eye movement sleep (NREMS) was delayed in response to 0.3 and 14 nmol GRF-antagonist, the duration of NREMS was decreased for one or more hours and after 14 nmol EEG slow wave amplitudes were decreased during NREMS in postinjection hour 1. The high dose of GRF-antagonist also suppressed REMS for 4 h, inhibited GH secretion, and elicited a slight biphasic variation in brain temperature. These findings, together with previous observations indicating a sleep-promoting effect for GRF, support the hypothesis that hypothalamic GRF is involved in sleep regulation and might be responsible for the correlation between NREMS and GH secretion reported in various species.

Animals↗