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Aim: The characteristics of visual evoked potentials (VEP) have been studied in diabetic patients with and without diabetic retinopathy., Material and Methods: Magnetic impulses (2.0 T1 at the height of impulse) have been delivered to the cerebellar surface transcranially using the "Neuro-MS/D", (Russia Federation). Delta- sleep inducing peptide ("Deltalycyn", "Biopharma", Russia Federation) was intranasally delivered in 30 min before photostress. Afterwards VEP have been registered every 20 s from the moment of photo stress during one minute., Results: An increase of the latency period and a reduction of the VEP amplitude have been recorded in the period following photo stress exposure of the macular part of the retina. The VEP characteristics restored to the initial level in 73.5 +/- 3.3 s from the photo stress moment in the control group; while in diabetic patients with retinopathy this index was 137.2 +/- 11.3 s. In the. presence of cerebellar transcranial magnetic stimulations (2.0 T1, 20 impulses) the VEP amplitude depression was less pro- nounced, and the restoration period of the VEP characteristics shortened to 110.3+ 12.7 s, while in deltalycyn treated patients restoration was observed in 95.1+ 6.8 s. Under condition of combined usage of deltalycyn and TMS period of restoration of VEP was shortened up to 82.5 +/- 6.5 s., Conclusions: Retinopathy development is linked to prolonged VEP latency period (P100), lowering of the N75-P100 amplitude, as well as to enlargement of the recovery period of the retina's functional capacity in patients suffering from the diabetes mellitus in the presence of photo stress. Superlatively administered deltalycyn and cerebellar transcranial magnetic stimulation facilitates a faster recovery of the retina's functional capacity in response to photo stress in diabetic patients with retinopathy. 3. Combined usage of deltalycyn and cerebellar transcranial stimulation caused the potentiated shortening of post-photo stress recovering of VEP in patients with diabetic retinopathy.

The aim of the work was investigation of both humoral and cell-mediated immunity together with leukocytes functional stability indexes in rats with the experimental contact dermatitis (ECD) in conditions of complex pharmacological correction using deltaran and melatonin. Experimental trials were performed under conditions of chronic experiment on model chrome-induced ECD. Both deltaran and melatonin either alone or in combination were used for complex pharmacological correction of humoral and cell-mediated immunity and also for stability of leukocytes. The data obtained showed the expressed disturbances of humoral and cell-mediated immunity and neutrophils' functional stability damage under conditions of chrome-induced ECD in rats. The revealed alterations in functional activity of the immune system were successfully corrected using the combined administration of deltaran and melatonin. The activity of medical complex had exponential character.

The characteristics of visual evoked potential (VEP) have been investigated in a group of 15 healthy volunteers (aged 31.7 ± 3.6 years) and 30 insulin-dependent patients (aged 32.1 ± 4.0 years) with diabetes mellitus, among which 15 patients suffered from diabetic retinopathy and 15 patients had no retinopathy. An increase in the latent period along with reduction of the VEP amplitude after photostress action upon the macular part of retina have been observed in patients with diabetes, these effects were more pronounced in the subgroup with retinopathy. The restoration of VEP characteristics in 73.5 ± 3.3 s from the moment of photostress was observed in the control group, while this index in both subgroups of diabetic patients without and with retinopathy was 88.7 ± 5.9 and 137.2 ± 11.3 s, respectively. Treatment with deltalicin (daily dose of 0.0003 g of delta sleep-inducing peptide intranasally for two months) decreased the latent period and led to less pronounced depression of VEP amplitude in patients with diabetic retinopathy, and reduced the period of restoration of VEP characteristics to 95.1 ± 6.8 s.

The effect of delta sleep-inducing peptide (DSIP) on the lymphoid structures of small intestine, was investigated. Studies were conducted on 42 male Wistar rats, which were previously assessed in an "open field" test. According to the results of the test, rats were divided into behaviorally active animals (prognostically resistant to stress) and passive ones (resistant to the effects of stress). As a stress, immobilization of the animals in pens with an electrical stimulation of their back for 1 hour, was used. Intraperitoneal injection of DSIP resulted in a reduction of eosinophil number in rats of all the experimental groups. After DSIP injection to the active rats of the control group, the increase in small and medium lymphocyte numbers was detected that was more expressed than in the passive rats. After an acute exposure of behaviorally active rats to stress, the number of the cells of lymphoid series was increased,mainly due to the increase in small and medium lymphocytes. In the group of passive rats, stress exposure and DSIP injection resulted in the increase of plasma cell number in all the duodenal mucosa structures studied.

Female SHR mice received 5-days long monthly courses of delta-sleep inducing peptide (DSIP) preparation "Deltaran" subcutaneously in dose 5 mkg/kg during all their lives. It was demonstrated, that last 10% (most aged) of mice which received Deltaran lived for 16% longer than the controls. They had significantly higher amount of vertical activity in the "open field" test, than the controls, starting from time when they were 6 months old and until their natural death. Mice of Deltaran group spent 73% more time in the open arms of elevated plus maze, and 9 times more often explored the extremities of this maze, than controls. Also Deltaran slowed the spontaneous carcinogenesis parameters. It's assumed that DSIP preparation "Deltaran" have geroprotective, anxiolytic and antitumor activity.

Introduction: We investigated the potential of delta sleep-inducing peptide (DSIP) and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DISP molecule substituted by beta-alanine) and tetrapeptide analogue DSIP1-4, to antagonize metaphit(1-1 (3-isothiocyanatophenl)-cvyclohexyl piperidine) induced generalized reflex audiogenic seizures in adult male Wistar albino rats., Material and Methods: Five groups of adult male Wistar rats were intraperitoneally treated with: (1) saline; (2) metaphit: (3) metaphit + DSIP, (4) metaphit + DSIPI-4 and (5) metaphit + DSIP-12. To examine the blocking effects of DSIP and its analogues on fully developed metaphit seizures, in the last three groups they were administered 8h after metaphit injection. The rats were stimulated using an electric bell (1003 dB, 5-8 kHz, 60 s) one hour after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recordings and power spectra three gold-plated screws were implanted into the skull., Results: In metaphit-treated animals EEGs appeared as polyspikes and spike-wave complexes, while power spectra were increasing. The incidence and severity of netaphit-induced audiogenic seizures reached a peak value at 7-12 h after injection. Both DSIP and DSIP analogues significantly increased power spectra of delta waves and decreased the incidence of seizures, as well as mean seizure grade and tonic component of metaphit-induced convulsions., Conclusion: Taken together, these results suggest that DSIP and its analogues should be considered as potential antiepileptic agents.

The medico-social significance of ischemic brain lesions, which are the most frequent cause of disablement and death in older people, stipulates the need for efficient means of prevention and correction of central nervous system disorders in case of ischemic brain lesions. The efficacy of Deltaran in the correction of disordered neuromediator balance in the brain of rats of different age groups was studied on the model of carotid arteries occlusion. Studies showed, that Deltaran exerts an anti-stress effect on old rats with left-side profile by altering the neuromediators' distribution in animals' brain under conditions of hypoxia. This enables to recommend Deltaran for further study as a neuroprotector.

An aim of the present study was a comparative investigation of a delta-sleep inducing peptide and the drug deltaran on the neural activity of the brain structures involved in emotional processing. Another goal was to analyze the possibility to prevent negative effects of emotional stress on brain ischemia using, along with deltaran, glycine and a delta-sleep inducing peptide. Deltaran and the delta-sleep inducing peptide exert in general similar effect on the burst activity of neurons in the dorsal hippocampus, hypothalamic paraventricular nucleus and ventral anterior thalamic nucleus, inducing amplification of the majority of recorded units. The activation of neuronal activity was seen mostly after the delta-sleep inducing peptide microiontophoresis in the dorsal hippocampus and after the deltaran application in the hypothalamic paraventricular nuclei. The index characterizing blood supply was significantly higher in all rats receiving deltaran as compared to the controls. Animals receiving deltaran survived experimental brain ischemia in 100% cases versus 38% in those not exposed to this drug.

The effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on metaphit-induced generalized, audiogenic seizure in adult rat males were compared. The animals were i.p. injected with: (1) Saline; (2) metaphit (mp, 10 mg kg(-1)); 3. metaphit (10 mg kg(-1)) and 8 h later with DSIP (0.1, 0.2, 0.4 or 1.0 mg kg(-1)), 4. metaphit (10 mg kg(-1)) and 8 h later with VPA (50, 75 or 100 mg kg(-1)); 5. DSIP alone (1.0 mg kg(-1)) and 6. VPA, alone (100 mg kg(-1)). The rats were exposed to sound stimulation at hourly intervals and the behavior and EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep-like pattern and spike-wave complexes with increased power spectra. Valproate and DSIP reduced the incidence of seizure and prolonged duration of latency in a dose-dependent manner. ED50 of valproate in the 1st hour after administration was 63.19 mg kg(-1) and that of DSIP 3.19 mg kg(-1) four hours after injection. This suggests that VPA, reached a peak of action immediately after the application, while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit seizure. None of the applied VPA and DSIP doses eliminated the metaphit-provoked EEG signs of epileptiform activity.

Local cerebral blood flow in the left hemisphere decreased most significantly in low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively increased blood flow in the left hemisphere and improved blood supply to neuronal activity unit of the brain in these animals. This drug prevented progressive decrease in local cerebral blood flow in both hemispheres during the acute stage of ischemia. The effect of Deltaran was related to modulation of collateral blood flow and adequate blood supply to neuronal activity unit in the brain tissue. Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of cerebral ischemia. The positive effect of Deltaran was more pronounced in the left hemisphere.

Quantitative interferometry showed that chronic amphetamine administration to August rats (2.5 mg/kg/day for 3 weeks) increased the area of neuronal cytoplasm and nuclei and content and concentrations of proteins in hippocampal CA3 neurons. These changes persisted after single injection of delta sleep-inducing peptide (60 microg/kg). The reaction of the entire neuronal population of hippocampal CA3 neurons to amphetamine is similar.

The effect of delta-sleep-inducing peptide (DSIP) on the anticonvulsive activity of a nonprotective valproate (VPA) dose in a metaphit model of generalized, reflex audiogenic seizures in adult Wistar rats was studied. The animals that received metaphit (10 mg/kg) were exposed to audiogenic stimulation (100 +/- 3 dB, 60 s) at hourly intervals. Metaphit-treated rats displaying seizures in 8 previous tests were i.p. injected with VPA (50 mg/kg) or DSIP (1.0 mg/kg) or their combination. Latency to seizure was behaviorally assessed. The EEGs and power spectra were recorded and analyzed. Neurotoxicity was evaluated by the chimney test. DSIP or VPA alone expressed no significant effect on the latency duration, but their combination significantly prolonged latency to seizure during 6 h after injection, while inducing no significant motor impairment. Neither the applied drugs nor their combination abolished metaphit-provoked EEG epileptiform activity. The results show that DSIP potentiated anticonvulsive effects of a nonprotective VPA dose in a metaphit model of audiogenic seizures without influencing its neurotoxicity., (Copyright 2006 S. Karger AG, Basel.)

Problem: Previous studies have shown that humoral, endogenous and somnogenic, delta sleep-inducing peptide (DSIP) has influence on insomnia, pain, adaptation to stress, epilepsy, etc. We investigated the potential of DSIP and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DSIP molecule substituted by beta-alanine) to antagonize metaphit (1-[1(3-isothiocyanatophenyl)-cyclohexyl]piperidine) induced generalized, reflex audiogenic seizures in adult male Wistar albino rats., Methods: The rats divided in four groups received (i.p.): saline; metaphit; metaphit+DSIP; and metaphit+DSIP-12, respectively. Metaphit-treated animals displaying seizure in eight previous tests received DSIP or DSIP-12 and afterwards audiogenic stimuli were applied at hourly intervals for the next 30 h. The animals were exposed to sound stimulation 60 min after metaphit administration and further on at hourly intervals. Incidence and severity of seizures were behaviorally analyzed. Selected EEGs and power spectra were recorded and analyzed., Results and Conclusions: Metaphit led to hypersynchronous epileptiform activity (polyspikes and spike-wave complexes) and increased power spectra 0.5-30 h after the treatment. Severity of metaphit seizures increased with time to reach the peak 7-12 h after injection. DSIP and DSIP-12 significantly (*P<0.05 and **P<0.01) increased in delta and theta frequency bands and decreased the incidence, mean seizure grade and duration of metaphit convulsions. The results suggest that DSIP and DSIP-12 may be considered as potential antiepileptics in the animal model, DSIP-12 being more efficient than DSIP.

Unlabelled: Delta-sleep induced peptide (DSIP) has a wide range of positive regulator properties. It is known as antioxidant, immunomodulator, antistressor and other, that important as for diabetes, and for aging mechanisms. Aim of the study was to investigate effects of treatment by DSIP-containing drug "Deltaran" in elderly diabetic patients., Materials and Methods: As the pilot study we examined 11 elderly diabetic patients (mean age 66.3 yr, BMI--28.5 kg/m2, duration of diabetes 12.5 yr). All patients receive 20 doses of DSIP-containing drug "Deltaran" daily. Tests was before and after 60 days after beginning treatment. Blood samples took before and after 60 minutes after standard carbohydrates breakfast., Results: After treatment were observed improvement of the parameters of quality of life on SCAG scale as the impairment of recent memory (p=0.003), mood depression (p=0.019), emotional lability (p=0.002) and anxiety (p=0.000). Also were observed improvement of quality of sleep and felling between meals in treating patients (p=0.010). Another positive tendencies consist of decrease of BP (ns), increase of ABI (ns), increase of pallestesia (p=0.017), decrease of MAU frequency (p=0.011) and decrease of glycaemia levels after load (p=0.033). And also after treatment were observed decrease of basal and reactive levels in blood of growth hormone (p=0.034 and p=0.005 accord.), insulin (ns), cortisol (ns) and on the contrary increase of dehydroepiandrosterone sulfate levels (ns). Main positive change observed in patients received only diabetic diet, where was a decrease of insulin resistance and in patients with latent autoimmune diabetes (type LADA), where was a increase insulin secretion and decrease of daily dose of insulin requiring., Conclusions: The pilot trial indicate beneficial antidiabetic and geroprotective effects of DSIP-contaning drug "Deltaran" in elderly diabetic patients.

The effects of delta sleep-inducing peptide (DSIP) on metaphit- (1-(1(3-isothiocyanatophenyl)-cyclohexyl) (piperidine)-) induced audiogenic seizures in adult male Wistar rats were studied. The animals were divided into four experimental groups: 1. saline injected; 2. metaphit administered (10 mg x kg (-1)); 3. metaphit administered plus DSIP injected (dose range 0.1-1 mg x kg (-1)) and 4. DSIP injected (1 mg x kg (-1)). Upon treatment, the rats were exposed to sound stimulation ( 100 +/- 3 dB, 60 s) at hourly intervals and the incidence and severity (running, clonus and tonus) of seizures were analyzed. In most animals, metaphit led to EEG abnormalities and elicited epileptiform activity recorded as spikes, polyspikes and spike-wave complex and increased power spectra. Time-course studies revealed the peak of convulsive activity 7-12 h after the injection in metaphit-treated rats. DSIP acted as an anticonvulsant and the most potent anticonvulsive dose of 1 mg x kg (-1)significantly increased power spectra of deltawaves (2-11 h) in comparison with the saline-control group and decreased the incidence and duration of convulsive response, as well as mean seizure grade of metaphit-induced convulsions. These results suggest that DSIP should be considered as having potential anticonvulsant activity in this animal model., (Copyright 2002 Elsevier Science Ltd.)

Experimental studies were carried out to investigate the neuroprotective effects of delta sleep-inducing peptide in animals with cerebral ischemia induced by bilateral compression of both carotid arteries, and to compare the efficacy of this peptide with that of MK-801. These studies led to the conclusion that the peptide had pronounced anti-ischemic effects, which were evident within 24 h and consisted of reductions in the severity of postural abnormalities in rats with bilateral cerebral ischemia, along with a reduction in lethality. Comparison of the efficacies of peptide and MK-801 showed the peptide to have the greater neuroprotective effect. These results are regarded as providing an experimental basis for using the peptide as a therapeutic agent in patients with stroke.

The ED100 of the NMDA inducing clonic seizures (0.53 mcg) or tonic extension of forelimbs (5.02 mcg) increased their efficiency 2.3-fold and 4.46-fold, resp., due to the delta-sleep-inducing peptide administration in rats. The data obtained suggests a neuroprotective effect of the peptide on agonists of excitatory amino acid receptors action.

An anti-ischemic effect of the delta-sleep-inducing peptide (DSIP) was found in rats. The DSIP effect was more obvious than that of the MK-801. The data obtained is discussed considering a possible use of the DSIP for brain stroke prophylaxis.

The GABAergic system was adequate altered after simultaneous use of delta-sleeping peptide and piracetam in intact animals: gamma-butyric acid was accumulated unidirectionally by inhibiting brain glutamate decarboxylase activity. Administration of the peptide caused a slight decrease in the levels of aspartic acid, while piracetam contributed to a marked accumulation of the amino acid. The antistressor and adaptive effects of each drug were augmented if they were given simultaneously before acute emotional stress developed in the animals during one-hour hypokinesia; these effects were expressed as stabilized balance of inhibitory and excitatory neurotransmitter amino acids.

Differences have been found in responses of the brain formations studied by some protein metabolic parameters. They manifest themselves both between the neurons of cortical and subcortical structures and between those of various morphofunctional types and affect the corrective action of delta-sleep peptide.

Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides.

Antiedematic effects of the drugs are connected with their action on the mediator systems. DSIP has a wide range of modulatory effects on the brain mediator systems. DSIP antiedematic effect was studied on the toxic brain edema-swelling (BES) model. Physical characteristics of the nervous tissue such as thickness and wetness were used as evaluation criteria. According to the findings, the doses of 75-100 micrograms/kg DSIP were optimal. It is suggested that DSIP effect on BES is multicomponent and rather complicated. Inhibition of serotonin, noradrenaline and histamine systems and activation of GABA-ergic system by DSIP act as a possible antiedematic mechanism.

The delta-sleep-inducing peptide (DSIP) suppressed seizure activity in the cat cortical strychnine-induced seizure foci. The DSIP delayed development of corazol kindling in rats, prevented seizure induced with bicucullin and other agents in mice. The DSIP effect was shown to be realised through the action upon reticular black substance. The DSIP seems to take part in endogenous control of the brain excitability.

The influence of delta sleep-inducing peptide (DSIP) on sleep was studied in 16 chronic insomniac patients according to a double-blind matched-pairs parallel-groups design. Subjects slept for 5 consecutive nights in the laboratory. Night 1 was used for adaptation, night 2 for baseline measurements. In the afternoon before the 3rd, 4th and 5th night, half of the patients received intravenously 25 nmol/kg body weight DSIP, and half of the patients a glucose solution (placebo). Measures for sleep structure, objective (polysomnography) and subjective sleep quality and for subjective tiredness were assessed. The results for objective sleep quality indicated higher sleep efficiency and shorter sleep latency with DSIP as compared to placebo. One measure of subjectively estimated tiredness decreased within the DSIP group. Data analysis suggested, however, that the statistically significant effects were weak and in part could be due to an incidental change in the placebo group. As none of the other measures, including subjective sleep quality, showed any change, it was concluded that short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit.

The influence of the delta-sleep inducing peptide (DSIP, 60 and 120 nmol/kg, intraperitoneally) on the content of substance P (SP) in rats hypothalamus was studied on males of August line. DSIP administration significantly increased the mean SP content in the hypothalamus and also its content in animals, stable and predisposed to emotional stress. Daily DSIP administration before putting the rats in conditions of stress increased the SP content in the hypothalamus decreased at the emotional stress. Preliminary single DSIP administration to the animals subjected to stress also increased the SP content. Single DSIP administration in a dose of 60 nmol/kg sharply reduced classical stress manifestations, such as hypertrophy of adrenals and thymus involution.

In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.

In acute and chronic animal (rabbits, rats) experiments it has been shown that delta-sleep producing peptide (DSPP) exerts a noticeable effect on the cardiac function and regulation. DSPP at a dose of 60 nm/kg can prolong the effects of vagus and inhibit those of sympathetic nerves on the cardiac function and, consequently, can influence the function of choline- and adrenergic transmitters. DSPP blocks pressor vascular reactions in response to direct electrical stimulation of ventromedian hypothalamus and thus increases the survival of animals exposed to an acute emotional stress. DSPP normalizes the electrical stability of the heart and produces an antiarrhythmic effect on ventricular ectopic beats that occur in response to emotional stresses. In view of this, DSPP can be recommended for clinical trials as a drug preventing cardiac arrhythmias in stressful situations.

In chronic experiments on rabbits, a delta-sleeping inducing peptide was tested for effects on the cardiac electric stability and onset of ventricular premature beats during experimental emotional stress. The peptide in a dose of 60 nm/kg was found to normalize the thresholds of ventricular fibrillation and its predictors and to decrease or abolish spontaneous ventricular premature beats occurring during the stress. This suggests that the delta-sleep-inducing peptide may be used to prevent cardiac arrhythmias during stresses.

The influence of delta-sleep inducing peptide (DSIP) upon seizures induced by corazol, bicuculline, picrotoxin, strychnine, thiosemicarbazide were investigated in experiments on F1(CBA X C57 BL/6) mice. It was shown that DSIP increased the latency of first seizure manifestation which were induced by corazol, bicuculline and picrotoxin and also resulted in a suppression of seizure severity of corazol and bicuculline induced seizures. Anticonvulsant action of DSIP was evident under the condition of the mild severity seizures development. The effect of DSIP was mostly pronounced in range of its doses from 10 to 100 mcg/kg. DSIP when combined with phenobarbital, carbamazepine, diphenylhydantoin or nicotinamide enhanced the antiepileptic effects of these anticonvulsant drugs.

A 47-year old woman patient suffering from chronic delayed sleep phase insomnia and low-dose benzodiazepine dependence was treated as an inpatient under close polygraphic control using DSIP (delta sleep inducing peptide) on an intensive-care basis for one week. This treatment resulted in advancing the main sleep phase by 5 hours, in an abrupt and complete withdrawal of flunitrazepam and restitution of a normal sleep profile. Actographic control during an after treatment week confirmed that the success was maintained.

In free behaviour experiments on rats it has been shown that the intraperitoneal injection of delta sleep-inducing peptide (DSIP) (100 micrograms/kg) suppressed penicillin-induced relatively moderate epileptic foci which generated spike potentials as well as severe foci with ictal epileptic discharges. In the experiments on cats it was shown that intravenous DSIP injection (100 micrograms/kg) suppressed strychnine-induced epileptic focus and complexes of epileptic foci.

The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue.

The effects of delta sleep-inducing peptide (DSIP), on the sleep cycle of insomniac patients were assessed by means of polysomnographic recordings. DSIP in a dose of 25 nmol/kg or a placebo was administered i.v. during four nights using a double-blind crossover design. The number of nocturnal awakenings, non-rapid-eye-movement (NREM) sleep latency, total waking time and waking time after sleep onset were decreased under DSIP treatment, but no significant differences were found in comparison to baseline or to double-blind placebo nights. Total sleep time and NREM sleep time were increased by the peptide. Their increase was related to increases in stage 2, while stage 1, slow wave sleep (stages 3 and 4) and rapid-eye-movement sleep were not modified. For NREM sleep time and stage 2 sleep differences between DSIP and a placebo were significant, but the same differences existed already for the baseline values. It can be concluded that sleep improvement under DSIP treatment is of little clinical significance.

Impaired daytime functions are a significant part of chronic insomnia besides sleep disturbance. Therefore, the effects of intermediate-term delta-sleep-inducing peptide (DSIP) administration on sleep and daytime performance were investigated in 14 middle-aged chronic insomniacs. DSIP was administered under placebo-controlled, double-blind conditions for 7 successive nights. Polysomnograms were obtained for placebo baseline, beginning and end of DSIP treatment, and one placebo posttreatment night; daytime psychological state and mental performance were extensively tested before and after 6 DSIP injections. The treatment substantially improved night sleep with the first and additionally with repeated doses. These effects were maintained for the first posttreatment (placebo) night. Efficiency of night sleep and daytime rest reached the levels of normal controls. Alertness and performance at daytime increased significantly. The study demonstrates the efficacy of DSIP for the treatment of impaired sleep and daytime functions as well.

The effects of DSIP on night sleep and on waking functions are demonstrated in double-blind studies in insomniacs, presenting influences of single dose treatments as well as of repeated injections. Moreover, a single case study describes the efficiency of DSIP on narcolepsy.

The immediate effects of one week of Delta Sleep-Inducing Peptide (DSIP) administration (6 X 30 nmol/kg b.w., i.v.) and late effects after a follow-up period of one week were investigated in a sleep laboratory study. The population of 18 chronic psychophysiological insomniacs was subdivided into two groups of middle-aged (29-59) and older (60-83) insomniacs. In the middle-aged insomniacs, improvement of sleep to normal values occurred by the end of DSIP administration and was maintained during the follow-up week. In the elderly insomniacs, who showed an initial sleep disturbance double as severe as the middle-aged group, the immediate effect was larger, but full normalization of sleep was only obtained by the end of the follow-up period. Although there was an interaction of sleep pathology and age, a regression analysis yielded clear evidence that the effects of DSIP were correlated to the degree of sleep disturbance. The whole sample of insomniacs showed normal sleep patterns at the end of the investigation.