Hinrich Cramer

Natural and melatonin-induced sleep in young chickens — A behavioral and electrographic study

Summary1.Natural sleep and waking states of young chickens were studied by polygraphic recording (EEG, EOG, EMG and ECG) together with behavioral observation. Effects of melatonin were observed.2.The sleep-wake periods of the chickens were analysed for three states: awake, slow wave sleep (SS) and paradoxical sleep (PS). Polygraphic characteristics of these 3 states were analogous to, though in several aspects different from, those in mammalians.3.The sleep states alternated irregularly at short intervals. SS usually did not last longer than 6 min without being interrupted by an episode of arousal or PS. PS appeared at irregular intervals usually lasting only 6–8 sec. Total duration of PS was 7.3±1.8% of total sleep time.4.Melatonin (0.01–0.06 mg/g) had a powerful sedative and hypnotic effect which appeared within 1–2 min after i. perit. injection and lasted for 30–60 min. Melatonin-induced sleep was characterized by slow EEG activity of high voltage similar to that in normal SS but with a higher incidence of 2–3 c/sec waves.5.Melatonin besides activating SS, delayed the appearence of the first PS episode and decreased total PS time.6.In melatonin sleep as in natural sleep the chickens were easily aroused by sensory stimuli both in behavior and electrographic pattern.7.Possible mechanisms related to sleep-inducing effects of melatonin are discussed.Zusammenfassung1.Das natürliche Schlaf und Wachverhalten von Küken wurde mit Verhaltensbeobachtung und polygraphischer Registrierung (EEG, EOG, EMG, ECG) untersucht und die Wirkung von Melatonin geprüft.2.Aufgrund des Verhaltens und polygraphischer Kriterien werden 3 Stadien unterschieden: Wachzustand, langsamer Wellen-Schlaf (SS) und paradoxer Schlaf (PS). Die polygraphischen Charakteristika der 3 Stadien entsprechen — mit Einschränkungen — denen der Säugetiere.3.Die Schlafstadien wechseln mit kurzen Intervallen. SS dauert in der Regel nicht länger als 6 min ohne durch Erwachen oder PS unterbrochen zu werden. PS-Phasen von nur 6–8 sec Dauer treten in unregelmäßigen Zeitabständen auf. Die Gesamtdauer des PS beträgt 7.3±1.8% der Gesamtschlafzeit.4.Melatonin (0.01–0.06 mg/g Körpergewicht) hat eine starke sedierende und hypnotische Wirkung, die 1–2 min nach intraperitonealer Injektion einsetzt und 30–60 min dauert. Der Melatonin-induzierte Schlaf ist ein Schlaf mit langsamen Wellen ähnlich dem normalen SS, jedoch mit einem höheren Anteil der 2–3/secWellen.5.Melatonin hat außer der schlafinduzierenden Wirkung einen hemmenden Effekt auf den PS mit verlängerter Latenz der 1. PS-Phase und Verminderung der Gesamt-PS-Zeit.6.Verhaltensmäßig und nach EEG-Kriterien sind die Hühnchen im Melatoninschlaf ebenso wie im natürlichen Schlaf durch sensorische Reize leicht erweckbar.7.Die der Schlafwirkung des Melatonins zu Grunde liegenden Mechanismen werden besprochen.

Huntington's chorea—Measurements of somatostatin, substance P and Cyclic nucleotides in the cerebrospinal fluid

SummarySomatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntingtons disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.ZusammenfassungBei 12 Patienten mit Chorea Huntington und 7 Nachkommen aus Chorea-Familien wurden im lumbalen Liquor die Konzentrationen von Somatostatin, Substanz P, zyklischem Adenosinmonophosphat und zyklischem Guanosinmonophosphat radioimmunologisch bestimmt und mit Werten neurologischer Kontrollpatienten verglichen. Während die Konzentration von Substanz P sich in allen Gruppen nicht signifikant voneinander unterschieden, waren die Konzentrationen von Somatostatin bei Patienten mit manifester Chorea und bei den Nachkommen hochsignifikant vermindert. Zyklisches Adenosinmonophosphat war nur bei weit fortgeschrittener Chorea signifikant herabgesetzt. Mögliche Beziehungen der Somatostatin-Verminderung zur Pathophysiologie der Chorea und der Verminderung des zyklischen Nukleotids zur Hirnatrophie werden diskutiert.

Accumulation of adenosine 3′,5′-monophosphate induced by catecholamines in the rat superior cervical ganglionin vitro

Abstract Levels of cyclic AMP are elevated rapidly in rat superior cervical ganglia incubated in medium containing low concentrations of isoprenaline, adrenaline and noradrenaline. Phenylephrine and dopamine increase cyclic AMP when used at higher concentrations. The moderate rise induced by dopamine has a slow onset and long duration; the peak accumulation induced by beta-adrenergic agents is rapid and short-lasting. Preincubation with propranolol completely suppresses the elevation of cyclic AMP levels induced by all the agents tested.

Somatostatin-like immunoreactivity and substance-P-like immunoreactivity in the CSF of patients with senile dementia of Alzheimer type, multi-infarct syndrome and communicating hydrocephalus.

SummaryThe concentrations of somatostatin-like immunoreactivity (SLI) and substance-P-like immunoreactivity (SPLI) in lumbar spinal fluid of patients with senile dementia of the Alzheimer type (SDAT), multi-infarct syndrome, communicating hydrocephalus and control patients were determined by specific radio-immunoassay. Mean SLI and SPLI levels were significantly lower in an aged control patient group (mean age 83.5±5.6 years) than in an adult control patient group (mean age 30.8±10 years). In the latter group SPLI levels correlated negatively with age. Mean SLI levels decreased with deterioration in SDAT patients by up to 33% in late dementia. SPLI correlated with SLI in SDAT patients but was decreased significantly only in late dementia patients. Moderate and insignificant decreases of SLI were observed in patients with multi-infarct syndrome or communicating hydrocephalus. Analysis of SLI by gel-permeation chromatography revealed molecular heterogeneity of SLI. At least four peaks of SLI were eluted, two of which had apparent molecular weights of about 10,000 and 15,500, possibly representing somatostatin precursors. The ratio of SRIF to SLI of higher molecular weight was increased in patients with dementia compared to control patients.

Formation, accumulation and release of adenosine 3′,5′-monophosphate induced by histamine in the superior cervical ganglion of the rat in vitro

Abstract 1. 1. Histamine increased endogeneous cyclic AMP levels and the conversion rate of 14 C-labeled adenine nucleotides to cyclic[ 14 C]AMP in rat superior ganglia in vitro in a dose-related manner, with half-maximal stimulation at a concentration of about 2·10 −4 M. 2. 2. The accumulation of cyclic AMP could be blocked by antihistamine drugs. The H 2 -blocker burimanide showed a strong stimulatory effect on adenylate cyclase in contrast to diphenhydramine. Practolol, a β-adrenergic antagonist, inhibited the accumulation of cyclic AMP induced by epinephrine, but not induced by histamine. 3. 3. Following stimulation of cyclic AMP formation in the ganglia, cyclic AMP concentrations also increased in the incubation medium, indicating overflow or release of the cyclic nucleotide from the ganglia. Marked release of cyclic[ 14 C]-adenine occured under control or stimulation conditions. 4. 4. Measurable amounts of cyclic AMP phosphodiesterase and lactate dehydrogenase activity were detected in the medium in the course of incubation of ganglia. Cyclic AMP phosphodiesterase activity slightly decreased initially on stimulation of adenylate cyclase by histamine. No efflux of ATP or [ 24 C]ATP was observed, except immediately after the transfer of ganglia from ice-cold to experimental (37°C) medium. 5. 5. p -(Di- n -popylsulfanoyl)-benzoic acid (10 −4 M) blocked the efflux of cyclic AMP by about 10%. It inhibited the accumulation by cyclic AMP induced by histamine, but not by epinephrine.

Effects of somatostatin on dopamine sensitive adenylate cyclase activity in the caudate-putamen of the rat.

SummaryThe effect of somatostatin-14 (SRIF) on dopamine-sensitive adenylate cyclase in caudateputamen pellets was studied in naive female rats, and in rats with chemical lesions of the nigrostriatal dopaminergic tract produced by injecion of 6-hydroxydopamine, or of the caudate-putamen itself produced by injection of kainic acid 3 week earlier. In unlesioned rats somatostatin at a concentration of 10−7 moles/1 inhibited adenylate cyclase activation by submaximal concentrations of dopamine, increasing the apparent Km but not altering Emax. In 6-hydroxydopamine lesioned rats somatostatin no longer influenced adenylate cyclase activity, whereas in kainic acid lesioned rats somatostatin still increased the apparent Km for dopamine activation. The effect of somatostatin in untreated and lesioned rats is compatible with a partial competitive antagonism to dopamine. Although the data from the lesioned rats present preliminary results, the dose response characteristics and the effects in lesioned animals suggest a more complex interaction, possibly by binding of somatostatin to an inhibitory subunit of regulatory adenylate cyclase components.

Immunoreactive Substance P and Somatostatin in the Cerebrospinal Fluid of Senile Parkinsonian Patients

The concentration of substance-P-like immunoreactivity (SPLI) and somatostatin-like immunoreactivity (SLI) in the lumbar spinal fluid of senile parkinsonian patients (mean age 77.6 +/- 6.7 years) and senile control patients (mean age 83.5 +/- 5.6 years) were determined by specific radioimmunoassays. Mean SPLI and SLI levels in the control group were 8.1 +/- 2.0 (SD) and 32.5 +/- 12.0 fmol/ml, respectively. The mean SPLI levels were not significantly different in the groups. The mean SLI level was significantly lower in the group of patients with Parkinsons disease (19.8 +/- 9.0 fmol/ml). A comparison with results in patients with senile dementia of Alzheimer type (SDAT) shows that, in addition to clinical and pathological correlations, Parkinsons disease of late onset may share a deficit in somatostatinergic neuromodulation with SDAT.

Somatostatin-like immunoreactivity in the cerebrospinal fluid of neurological patients

Using a specific radioimmunoassay we have measured somatostatinlike immunoreactivity (SLIR) of CSF in patients with brain atrophy, spinal spasticity, seizures, brain tumors and inflammatory disorders.Patients with marked brain atrophy had significantly decreased somatostatin levels in CSF. In patients with spinal spasticity significantly higher levels were observed. Seizure patients had reduced levels but the difference was not significant. In patients with inflammatory disorders and malignant brain tumors SLIR levels were significantly elevated but not in patients with benign brain tumors. A possible pathophysiologic meaning of SLIR in spasticity and seizures is discussed. The altered levels in brain atrophy, tumors and inflammatory disorders are probably indirect signs of altered somatostatin turnover or increased somatostatin leakage from damaged CNS.ZusammenfassungBei neurologischen Patienten wurde die Immunreaktivität für Somatostatin (SLIR) im Liquor cerebrospinalis mit einem spezifischen Radioimmuntest gemessen. Patienten mit Hirnatrophie hatten signifikant verminderte, Patienten mit spinaler Spastik signifikant erhöhte SLIR-Werte. Auch bei Patienten mit malignen Hirntumoren und mit entzündlichen Prozessen fanden sich erhöhte Werte, während Patienten mit Epilepsie gering und nicht signifikant erniedrigte SLIR-Spiegel hatten. Die mögliche pathophysiologische Bedeutung einer erhöhten Aktivität spinaler somatostatinerger Neurone bei Spastik und Ursachen der Änderungen bei cerebralen Prozessen werden diskutiert.

Effects of haloperidol on somatostatin-like immuno-reactivity in the CSF of schizophrenic patients

The levels of somatostatin-like immunoreactivity (SLI) were determined in the cerebrospinal fluid (CSF) of 14 schizophrenic patients before and after 3 weeks on haloperidol treatment. Baseline levels of SLI correlated negatively with psychopathological items on the Brief Psychiatric Rating Scale related to psychotic productivity. SLI levels increased after haloperidol treatment, but this increase did not correlate with psychopathological improvement. A difference in the ratio of larger and smaller molecular forms of the peptide was found before and after treatment. The drug-free samples showed a preponderance of the larger molecular forms, resulting in a ratio of 4:1, whereas the haloperidol-treated samples showed an equal distribution of both species.

Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease.

SummaryThe concentrations of somatostatin-like immunoreactivity (SLI) in lateral ventricular fluid of patients with extrapyramidal motor disease were determined by specific radio-immunoassay. Mean SLI levels were significantly lower in patients with Parkinsons disease (mean ± SEM); 42.9±2.9 fmol/ml) and in patients with dystonic syndromes (39.4±3.2) than in patients with benign essential tremor (65.3±9.7). The lowest levels were found in patients with athetosis (34.7±5.4). In parkinsonian patients somatostatin levels correlated with the degree of akinesia, rigidity and autonomic disturbances.