Biomedical subjects

I V Zhdanova

Publications and source records attributed to I V Zhdanova.

At least 19 recordsLinked to original sources

PubMed2005

Melatonin-evoked potentiation of the juvenile rat tail artery neurogenic reactivity depends on degree of the change in the reactivity.

AIM: Dependence of the melatonin-evoked potentiation of the rat tail artery neurogenic reactivity on degree of the change in the reactivity was studied. METHOD: Electrical field stimulation-evoked contractile response of the juvenile rat tail artery segment under isometric conditions was recorded. 0.1 mum melatonin was administered after the change in the response produced both spontaneously and by acidification (pH 6.6) or alkalinization (pH 7.8) of the solution. RESULTS: During the course of experiment, the contraction force continuously declined, being reduced by 12 +/- 5, 24 +/- 7 and 32 +/- 6% at 20, 70, and 170 min after beginning of experiment, respectively. Melatonin applied at these time points increased the contraction by 20 +/- 5, 41 +/- 10, and 48 +/- 8%, respectively, relative to control. This increase in potentiating effect of melatonin during the course of experiment was not because of sensitization of the segment to the hormone. Acidosis-induced considerable decline in neurogenic contraction was counteracted by melatonin, while after alkalosis-induced augmentation in the contraction the hormone was not effective. Melatonin increased the artery response to 0.1 mum noradrenaline. CONCLUSION: These data suggest that melatonin can restore an attenuated neurogenic reactivity of the juvenile rat tail artery. The effect is more pronounced with further decrease in reactivity and might be due to a change in sensitivity of the post-junctional membrane to noradrenaline.

Animals↗

PubMed2003

[Effect of melatonin on neurogenic vasoreactivity: formation and modulation of the vessel response].

The effect of melatonin (0.1 microM) on the contractile response to electrical field stimulation (EFS) of the juvenile rat tail artery segment was studied. The spontaneous decrease in reactivity of the segment observed in the course of our experiments was accompanied with a melatonin-evoked increase in the reactivity which was proportional to this decrease and was not connected with a sensitization of the segment to the substance. Perfusion of the segment with an acidic solution leads to a more pronounced inhibition of the response as well as to a greater melatonin-evoked protentiation of the response. Noradrenaline-evoked response was not augmented by melatonin. The results suggest that the potentiating effect of melatonin on the EFS-evoked response of the juvenile rat tail artery depends on degree of the change in the artery reactivity and was not due to change in sensitivity of postjunctional membrane to noradrenaline.

Animals↗

PubMed2002

[Effect of fluvastain and its combination with aspirin and trental on hemostasis and microcirculation in atherosclerosis].

AIM: To assess effects of fluvastatin monotherapy and combined therapy with aspirin and trental on hemostasis and microcirculation in atherosclerosis. MATERIAL AND METHODS: Hemostasis and microcirculation were studied in 68 patients with coronary atherosclerosis and aortic atherosclerosis on fluvastatin monotherapy and on combined therapy fluvastatin + aspirin + trental. RESULTS: Hypolipidemic treatment with fluvastatin reduced thrombogenic blood potential due to enhancement of plasmic fibrinolytic activity [the time of XII-a dependent fibrinolysis decreased by 33% (p < 0.05)], decreased thrombinemia [blood level of soluble fibrin-monomeric complexes fell by 44% (p < 0.05)] and reduced stimulated platelet aggregation: by 18.2% in response to ADP (p < 0.05) and by 11% in response to adrenalin (p < 0.05). CONCLUSION: Correction of lipid metabolism and blood hypercoagulation improved microrheology. Combination of fluvastatin with aspirin made platelet aggregation reduction in response to both inductors faster and more stable, while combination of fluvastatin with trental contributed to better results in microcirculation improvement.

Adult↗

PubMed2001

Melatonin promotes sleep-like state in zebrafish.

The sleep-promoting effect of the pineal hormone melatonin in humans is known for decades. However, the mechanisms of this phenomenon remain obscure, mainly due to lack of a simple, genetically tractable, animal model. We now report that melatonin promotes sleep-like state in a diurnal lower vertebrate, zebrafish (Danio rerio), and this effect is mediated through activation of specific melatonin membrane receptors. Furthermore, our data show that the sleep-like state in zebrafish has fundamental similarities with sleep in mammals, including characteristic postures, elevated arousal threshold to sensory stimulation and a compensatory rest rebound following rest deprivation, and can be induced by conventional hypnotics, diazepam and sodium pentobarbital. Collectively, these data indicate that melatonin is evolutionary conserved sleep-promoting agent in diurnal species and suggest that zebrafish provide an efficient animal model for studying the molecular mechanisms of sleep regulation and for screening new types of hypnotic medications.

Animals↗

PubMed2001

Melatonin treatment for age-related insomnia.

Older people typically exhibit poor sleep efficiency and reduced nocturnal plasma melatonin levels. The daytime administration of oral melatonin to younger people, in doses that raise their plasma melatonin levels to the nocturnal range, can accelerate sleep onset. We examined the ability of similar, physiological doses to restore nighttime melatonin levels and sleep efficiency in insomniac subjects over 50 yr old. In a double-blind, placebo-controlled study, subjects who slept normally (n = 15) or exhibited actigraphically confirmed decreases in sleep efficiency (n = 15) received, in randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3.0 mg) orally 30 min before bedtime for a week. Treatments were separated by 1-wk washout periods. Sleep data were obtained by polysomnography on the last three nights of each treatment period. The physiologic melatonin dose (0.3 mg) restored sleep efficiency (P < 0.0001), acting principally in the midthird of the night; it also elevated plasma melatonin levels (P < 0.0008) to normal. The pharmacologic dose (3.0 mg), like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia and caused plasma melatonin to remain elevated into the daylight hours. Although control subjects, like insomniacs, had low melatonin levels, their sleep was unaffected by any melatonin dose.

Age Factors↗

PubMed2000

Chronic cocaine treatment induces dysregulation in the circadian pattern of rats' feeding behavior.

The effects of protracted cocaine administration (15 mg/kg i.p., twice a day for 9 days) on the circadian pattern of feeding behavior was studied in individually housed male Sprague-Dawley rats, maintained under a 12:12 light:dark cycle. Water and food were available ad libitum and food intake was measured twice a day before, during and after withdrawal of cocaine (or saline) treatment. Neither total 24-h food intake, nor body mass at the end of the experiment, was significantly different between cocaine-treated and control animals. However, cocaine administration affected the temporal distribution of food consumption. During the dark (activity) phase, rats receiving cocaine injections consumed significantly less food than control animals, and this effect persisted for up to 3 days of cocaine withdrawal. During the light (rest) phase, cocaine administration promoted food consumption and a significantly higher food intake was also observed during the first five cocaine withdrawal days. Continuous monitoring of locomotor activity did not reveal significant changes in the circadian pattern of activity between the two experimental groups during different treatment periods, except for an acute increase in locomotion within an hour after daytime cocaine injection. The results of this study demonstrate that sub-chronic cocaine administration alters the circadian pattern of rats' feeding behavior.

Animals↗

PubMed2000

Melatonin treatment attenuates symptoms of acute nicotine withdrawal in humans.

Nicotine withdrawal is typically associated with negative changes in mood and performance, which often lead to relapse. We tested whether an oral 0.3-mg dose of melatonin administered 3.5 h after the nicotine withdrawal, and increasing circulating melatonin concentrations within the physiological range, affects the symptoms of acute 10-h (0800-1800 h) nicotine withdrawal in regular smokers. Self-reported ratings of mood, sleepiness, and cigarette craving were assessed hourly, using 17 visual analog scales (VAS). Computerized Four-Choice Reaction Time (FCRT) and Simple Auditory Reaction Time (SART) tests were used to assess performance every 2 h. Saliva samples were collected hourly, and salivary melatonin levels were measured using supersensitive radioimmunoassay. Compared with the placebo, melatonin treatment significantly reduced self-ratings of "anxious," "restless," "tense," "irritable," "angry," "depressed, " "impatient," and "craving for cigarettes." Melatonin treatment did not significantly change the responses on the performance tests used. These data suggest that melatonin can help to counteract the acute effects of smoking cessation on mood.

Adult↗

PubMed2000

Melatonin, sleep, and circadian rhythm disorders.

In the 1970s and early 1980s, neuroendocrinology was viewed by many neuroscientists as a ""window to the brain" to an understanding of brain function." In psychiatry, many have viewed sleep physiology as a window in biological psychiatry. This is, in part, because sleep is one of the few easily quantifiable functions of interest to psychiatrists. Melatonin is a hormone with powerful effects on behavior particularly circadian and sleep behavior. In contrast with other hormones, the pathophysiology and pathology of abnormal melatonin secretion is poorly understood. In this article, we document the well-established phase-shifting and sleep-promoting effects of melatonin and discuss some implications for neuropsychiatrists when the neurophysiology of melatonin goes array. It is both striking and in some ways not surprising that the majority of patients with phase delay syndrome described in our research studies have been misdiagnosed as having depression. The reason for this is elucidated in this article and the information concerning this condition may be helpful to many who are relatively unfamiliar with this particular sleep disorder. We can anticipate that patients with specific neurological disorders may have changes in their melatonin secretion and future research, for example in patients with head injury and conditions such as retinitis pigmentosa may be the basis for reviews a few years hence.

Brain↗

PubMed1999

Nocturnal increase in plasma cGMP levels in humans.

The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels.

Area Under Curve↗

PubMed1999

Effects of melatonin ingestion on cAMP and cGMP levels in human plasma.

The effects of daytime melatonin treatment (0.3 mg) on cAMP and cGMP levels in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were investigated in 14 normal human subjects (age+/-s.e.m. 26.2+/-3. 2 years). Plasma levels of cAMP, cGMP and melatonin were measured before and at intervals for 3 h after the treatment was administered at 1300 h. Plasma melatonin concentrations reached peak levels 1 h after the treatment (mean+/-s.d. 182.3+/-43.5 pg/ml). The mean areas under the curve (AUC) for the time-cGMP concentration curves in PPP and in PRP were significantly increased after melatonin treatment compared with those observed after placebo treatment (P=0.001). No significant difference in cGMP levels was observed between PPP and PRP. Increase in self-reported sleepiness after melatonin treatment positively correlated with increase in plasma cGMP levels (r=0.92). The mean AUC for the time-cAMP concentration in PRP, but not in PPP, was increased 1 h after melatonin treatment compared with that observed after placebo treatment, but not thereafter. No correlation between individual PRP or PPP cAMP levels and subjective sleepiness was observed. These results demonstrate a stimulating effect of melatonin treatment on plasma cGMP levels in humans and suggest a correlation between the increase in circulating cGMP levels and the sleep-promoting effect of the pineal hormone.

Administration, Oral↗

PubMed1998

Behavioral effects of melatonin treatment in non-human primates.

Melatonin treatment has been shown to induce sleepiness and promote sleep in humans. In order to understand the mechanisms by which melatonin acts on human sleep and behavior, it would be useful to have an animal model in which the physiological nocturnal increase in melatonin secretion correlated with nocturnal sleep, i.e., a diurnal species. In this pilot study the oral administration of melatonin to two Pigtail macaques (Macaca Nemestrina) at different times of the day significantly decreased motor activity and promoted earlier sleep onset, as measured actigraphically. The decline in the animals' motor activity occurred within 25-40 min after melatonin ingestion. The duration of motor inhibition was dose dependent. Administration of a 0.05 mg dose induced serum melatonin levels comparable to the peak physiologic concentrations reported in untreated humans and the non-human primates. These data suggest that melatonin may modulate motor activity and sleep pattern in certain diurnally-active primates.

Administration, Oral↗

PubMed1997

Efficacy of melatonin as a sleep-promoting agent.

Numerous studies have demonstrated sleep-promoting effects of melatonin treatment in humans, as evidenced by subjects' self-reports, polysomnographic recordings, and continuous actigraphic registration of motor activity. The sleep-promoting effects of either physiological or pharmacological doses of melatonin typically are observed within 1 h following treatment regardless of the time of melatonin administration. This fact indicates the acute nature of this effect of melatonin on sleep, independent of any effect of the melatonin treatment on circadian organization. This article considers a dose dependency of melatonin effects on sleep, interindividual variability, and age-related differences in circulating melatonin levels produced in response to a given dose of the hormone. Possible side effects of melatonin treatment, and the use of an animal model to serve as a guide in the development of therapeutic applications, also are considered.

Animals↗

PubMed1997

Melatonin: a sleep-promoting hormone.

This review discusses the issue of a dual effect of melatonin on sleep: acute sleep promotion that typically occurs within one hour of administration, and the ability to alter the phase of an underlying circadian pacemaker after a repeated melatonin treatment. The authors suggest that both mechanisms are at work, that they are complementary, and that they may manifest jointly or separately. The review provides some basic information on melatonin, an overview of the literature, and the authors' experience in studying the acute effects of melatonin treatment in humans of different age groups. This review also illustrates the authors' cautious attitude toward melatonin treatment that induces supraphysiologic circulating levels of the hormone.

Adult↗

PubMed1996

Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans.

Low oral doses of melatonin raise serum melatonin concentrations to those normally occurring nocturnally and facilitate polysomnographically assessed sleep onset when given at different time points throughout the day, without altering mood or performance on the morning following treatment. In the present study, 12 young healthy volunteers, free of sleep disturbances, received 0.3 or 1.0 mg of melatonin or placebo at 2100 hours, 2-4 hours prior to their habitual bedtime. Polysomnographic recording of overnight sleep began at 2200 hours and continued until 0700 hours the following morning, when subjects were awakened. Sleep onset latency and latency to stage 2 sleep were significantly decreased as a result of melatonin treatment. Neither dose of melatonin significantly altered sleep architecture. Administration of the lower dose of melatonin (0.3 mg) at 2100 hours elevated serum melatonin to levels within the normal nocturnal range (113 +/- 13.5 pg/ml) at the time the sleep test was initiated. Neither melatonin dose caused "hangover effects", as assessed by self-reports or by mood and performance tests administered on the morning following treatment. These observations provide additional evidence that nocturnal melatonin secretion has a sleep-promoting function. They also indicate that an increase in serum melatonin concentrations, within the normal physiologic range, does not significantly alter sleep architecture in subjects with normal sleep who receive the treatment several hours prior to their habitual bedtime.

Administration, Oral↗

PubMed1995

Sleep-inducing effects of low doses of melatonin ingested in the evening.

We previously observed tht low oral doses of melatonin given at noon increase blood melatonin concentrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using and involuntary muscle relaxation test. In this study we examined the induction of polysomnographically recorded sleep by similar doses given later in the evening, close to the times of endogenous melatonin release and habitual sleep onset. Volunteers received the hormone (oral doses of 0.3 or 1.0 mg) or placebo at 6, 8, or 9 PM. Latencies to sleep onset, to stage 2 sleep, and to rapid eye movement (REM) sleep were measured polysomnographically. Either dose given at any of the three time points decreased sleep onset latency and latency to stage 2 sleep. Melatonin did not suppress REM sleep or delay its onset. Most volunteers could clearly distinguish between the effects of melatonin and those of placebo when the hormone was tested at 6 or 8 PM. Neither melatonin dose induced "hangover" effects, as assessed with mood and performance tests administered on the morning after treatment. These data provide new evidence that nocturnal melatonin secretion may be involved in physiologic sleep onset and that exogenous melatonin may be useful in treating insomnia.

Administration, Oral↗

PubMed1994

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

Adolescent↗

PubMed1991

[Changes in the emotionally conditioned behavior of rats under the influence of the hexapeptide fragment GLLDLK of the protein inhibitor of diazepam binding].

It is shown that suboccipital injection of 100 micrograms of the gexapeptide GLLDLK (the fragment of endogenous peptide--the inhibitor of diazepam binding) modified (for 1-3 days) the emotionally conditioned behaviour of the rats (the test of "emotional resonance"). This modification was realized in some reinforcement of different behavioural patterns and had signs of anxiety and depression. In the test "social hierarchy" the injection of GLLDLK didn't change significantly the hierarchy in the whole rat society, but in the recipient behaviour the exploratory activity has been changed, the time of grooming increased and the quantity of social contacts decreased.

Animals↗

PubMed1986

[Type of behavior and superoxide dismutase activity in the brain of rats (a comparison of 2 Tryon strains)].

Differences in the type of behaviour in capable ("maze-bright") and incapable ("maze-dull") Tryon rats have been demonstrated in the situation with pain-irritated partner by the method of "emotional resonance". Most "bright" rats belonged to the type not avoiding the signals of another pain-irritated rat, they revealed a persistent ecologically defensive reaction of preferring a small closed space. The type of anxiety behaviour prevailed in the group of "dull" rats. In the open field test "bright" rats were characterized by low locomotor activity and high level of defecation and "dull" rats by high activity and low defecation. Increased levels of superoxide dismutase activity and high content of thiobarbituric acid-reactive material were observed in brains of dull rats. The interrelations between behavioural and molecular levels of defensive response to stress is discussed.

Animals↗