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1.
Psychiatry Res ; 291: 113239, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593854

RESUMO

It has been established that 4.4 to 20% of the general population suffers from a major depressive disorder (MDD), which is frequently associated with a dysregulation of normal sleep-wake mechanisms. Disturbances of circadian rhythms are a cardinal feature of psychiatric dysfunctions, including MDD, which tends to indicate that biological clocks may play a role in their pathophysiology. Thus, episodes of depression and mania or hypomania can arise as a consequence of the disruption of zeitgebers (time cues). In addition, the habit of sleeping at a time that is out of phase with the body's other biological rhythms is a common finding in depressed patients. In this review, we have covered a vast area, emerging from human and animal studies, which supports the link between sleep and depression. In doing so, this paper covers a broad range of distinct mechanisms that may underlie the link between sleep and depression. This review further highlights the mechanisms that may underlie such link (e.g. circadian rhythm alterations, melatonin, and neuroinflammatory dysregulation), as well as evidence for a link between sleep and depression (e.g. objective findings of sleep during depressive episodes, effects of pharmacotherapy, chronotherapy, comorbidity of obstructive sleep apnea and depression), are presented.

2.
Int J Neurosci ; : 1-14, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31903819

RESUMO

Background: Several studies have established a positive relationship between sleep difficulties and symptomatology in ASD children. The rationale for this review is to describe and discuss the sleep difficulties, which are one of the significant complications associated with autism spectrum disorder (ASD).Purpose: Many types of sleep disorders have been reported in ASD individuals, but still lack a comprehensive study and in-depth analysis. Despite the contribution of sleep problems to the overall symptoms of ASD, the symptoms of disturbed sleep experienced by many affected patients have only recently started to receive attention from clinicians and family members.Materials and methods: This narrative overview has been prepared based on searching standard research databases with specific keywords; b. Additional search was made using the bibliographies of the retrieved articles; and c. author's collection of relevant peer-reviewed articles. Once selected, manuscripts are then compared and summarized based on the author's perspective. Results are based on a qualitative rather than a quantitative level.Results: This article highlights the role of sleep in the brain and neural development of children and emphasizes that the intensity of sleep problems is associated with an increased occurrence of ASD symptoms. It also suggests the significance of treating sleep problems in ASD individuals.Conclusions: The review provides broader perspectives and a better understanding of sleep problems in pathophysiology, mechanism, and management with respect to ASD individuals. Finally, the implications for clinical practice and future agendas have also been discussed.

3.
World J Biol Psychiatry ; 21(2): 80-90, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30058415

RESUMO

Background: Sleep disturbances are a common symptom of major depressive disorder (MDD). Sleep is highly regulated by circadian rhythms, controlled by circadian genes, that act through a series of feedback loops to regulate the sleep-wake cycle.Objectives: To the best of our knowledge, a systematic review regarding the core circadian genes and their role in MDD has not been published recently. Also, a review of these genes and their role in sleep disturbances in depressed individuals appears to have never been done. We decided to integrate both concepts into one comprehensive review.Method: The review was done using the appropriate search terms in the following search engines: OVID Medline, Embase, PsycINFO and Pubmed.Results: Based on the data reviewed, none of the circadian genes appear to be associated with MDD, but some are more promising than others. These genes are: CRY1, CRY2, PER2 and NPAS2. When investigating the role of circadian genes in sleep disturbances among individuals with MDD, the most promising candidate gene is TIMELESS. Although the results in this area are limited.Conclusion: Given the promising leads from this review, future studies should investigate circadian genes in sleep disturbances among the depressed population.

5.
J Circadian Rhythms ; 16: 4, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30210564

RESUMO

In recent years, there has been an increased prevalence of type 2 diabetes mellitus (T2DM) and depression across the world. This growing public health problem has produced an increasing socioeconomic burden to the populations of all affected countries. Despite an awareness by public health officials and medical researchers of the costs associated with these diseases, there still remain many aspects of how they develop that are not understood. In this article, we propose that the circadian clock could be a factor that coordinates both the neurobehavioral and metabolic processes that underlie depression and T2DM. We propose further that this perspective, one which emphasizes the regulatory effects of clock gene activity, may provide insights into how T2DM and depression interact with one another, and may thus open a new pathway for managing and treating these disorders.

6.
Eur Arch Psychiatry Clin Neurosci ; 268(2): 107-118, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28894915

RESUMO

Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: "chronobiology," "mood," "sleep," and "circadian rhythms." We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.


Assuntos
Transtornos Cronobiológicos/etiologia , Fenômenos Cronobiológicos/fisiologia , Transtornos do Humor/fisiopatologia , Antipsicóticos/uso terapêutico , Transtornos Cronobiológicos/tratamento farmacológico , Fenômenos Cronobiológicos/efeitos da radiação , Humanos , Transtornos do Humor/terapia , PubMed/estatística & dados numéricos
7.
Prog Neuropsychopharmacol Biol Psychiatry ; 80(Pt C): 189-204, 2018 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-28433459

RESUMO

Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/patologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/patologia , Terapia de Alvo Molecular/métodos , Degeneração Neural/patologia , Disfunção Cognitiva/complicações , Transtorno Depressivo/complicações , Humanos
8.
J Cardiovasc Pharmacol Ther ; 22(2): 122-132, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27450357

RESUMO

The possible therapeutic role of melatonin in the pathophysiology of coronary artery disorder (CAD) is increasingly being recognized. In humans, exogenous melatonin has been shown to decrease nocturnal hypertension, improve systolic and diastolic blood pressure, reduce the pulsatility index in the internal carotid artery, decrease platelet aggregation, and reduce serum catecholamine levels. Low circulating levels of melatonin are reported in individuals with CAD, arterial hypertension, and congestive heart failure. This review assesses current literature on the cardiovascular effects of melatonin in humans. It can be concluded that melatonin deserves to be considered in clinical trials evaluating novel therapeutic interventions for cardiovascular disorders.

9.
Eur J Pharmacol ; 762: 42-8, 2015 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-26004526

RESUMO

The last decade has witnessed the emergence of new chronopharmacological perspectives. In the case of sleep disorders, the accumulating evidence suggests that even a minor dysfunction in the biological clock can impact broadly upon body physiology causing increases in sleep onset latency, phase delays or advances in sleep initiation, frequent nocturnal awakenings, reduced sleep efficiency, delayed and shortened rapid eye movement sleep and increased periodic leg movements, among others. Thus, restoration of the adequate circadian pattern of proper sleep hygiene, targeted exposure to light and the use of chronobiotic drugs, such as melatonin, which affect the output phase of clock-controlled circadian rhythms, can help to recover the sleep-wake cycle. The optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms is known as chronotherapeutics. While chronotherapeutical approaches have been particularly successful in the treatment of hypertension, allergies and some forms of cancer, a time-dependent pharmacological approach can be also effective when dealing with sleep disruptions like insomnia. A large proportion of patients under benzodiazepine (BZD)/Z drug treatment fail to achieve a complete and sustained recovery and are left with residual symptoms, like tolerance or dependency, that make relapse or recurrence more likely, and poorer quality of life a reality. Thus the chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. This short review discusses available data on the efficacy of melatonin to reduce chronic BZD use in insomnia patients.


Assuntos
Cronoterapia Farmacológica , Melatonina/farmacologia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Animais , Humanos , Melatonina/uso terapêutico , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos
10.
Prog Neurobiol ; 127-128: 46-63, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25697044

RESUMO

Melatonin is known to possess several properties of value for healthy aging, as a direct and indirect antioxidant, protectant and modulator of mitochondrial function, antiexcitotoxic agent, enhancer of circadian amplitudes, immune modulator and neuroprotectant. It is levels tend to decrease in the course of senescence and are more strongly reduced in several neurodegenerative disorders, especially Alzheimer's disease, and in diseases related to insulin resistance such as diabetes type 2. Although the role of melatonin in aging and age-related diseases has been repeatedly discussed, the newly emerged concept of inflammaging, that is, the contribution of low-grade inflammation to senescence progression has not yet been the focus of melatonin research. This review addresses the multiple protective actions of melatonin and its kynuramine metabolites that are relevant to the attenuation of inflammatory responses and progression of inflammaging in the brain, i.e. avoidance of excitotoxicity, reduction of free radical formation by support of mitochondrial electron flux, prevention of NADPH oxidase activation and suppression of inducible nitric oxide synthase, as well as downregulation of proinflammatory cytokines. The experimental evidence is primarily discussed on the basis of aging and senescence-accelerated animals, actions in the immune system, and the relationship between melatonin and sirtuins, having properties of aging suppressors. Sirtuins act either as accessory components or downstream factors of circadian oscillators, which are also under control by melatonin. Inflammaging is assumed to strongly contribute to neurodegeneration of the circadian master clock observed in advanced senescence and, even more, in Alzheimer's disease, a change that affects countless physiological functions.


Assuntos
Encéfalo/imunologia , Melatonina/metabolismo , Envelhecimento/fisiologia , Animais , Humanos , Imunossenescência/fisiologia , Doenças Neurodegenerativas/metabolismo , Neuroimunomodulação/fisiologia
11.
Neuropsychiatr Dis Treat ; 10: 2325-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25525361

RESUMO

BACKGROUND: Sleep-wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of Per3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India. METHODS: Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. Per3 genotyping was performed on DNA by polymerase chain reaction using specific primers. RESULTS: An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08-2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (χ (2)=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls. CONCLUSION: The occurrence of the five repeat allele of Per3 may be a risk factor for BD-I onset in this ethnic group.

12.
Horm Mol Biol Clin Investig ; 18(3): 145-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25390010

RESUMO

BACKGROUND: A number of observations support the involvement of circadian clock genes in the regulation of metabolic processes. One of these circadian genes, Per3, exhibits a variable number tandem repeat length polymorphism, consisting of two alleles, namely four and five repeat alleles, in its exon 18. The objective of this study was to examine the existence of Per3 variants in patients with type 2 diabetes mellitus (T2DM) as compared to a non T2DM control group. METHODS: Intravenous blood samples were collected to obtain white blood cells from 302 T2DM patients and 330 non-diabetic, age- and sex-matched, individuals. Per3 genotyping was performed on DNA by polymerase chain reaction. RESULTS: Frequency of five repeat allele was higher, and that of four repeat allele lower, in T2DM patients as compared to non-diabetic controls (χ2=6.977, p=0.0082) CONCLUSIONS: The results indicate an association of Per3 five repeat allele with T2DM occurrence and suggest that individuals with five repeat allele may be at a greater risk for T2DM as compared to those carrying the four repeat allele.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteínas Circadianas Period/genética , Polimorfismo Genético , Adulto , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Circadianas Period/sangue
13.
Diabetes Res Clin Pract ; 106(2): 182-90, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25172521

RESUMO

The circadian clock drives a number of metabolic processes including energy intake, storage and utilization coupled with the sleep/wake cycles. Globally, the increasing prevalence of type 2 diabetes (T2DM) has become a significant international public health concern. In view of the heavy societal burden caused by diabetes, and further, to reduce its growing incidence, it is clearly essential to understand the causes of this disease and to devise more effective strategies for its treatment. Although many factors cause T2DM, this article centers on the role of circadian regulation of metabolism. The correlation between the increased occurrence of T2DM and the ubiquity of modern social pressures such as 24/7 lifestyles as well as nocturnal lighting conditions point strongly to the hypothesis that malfunctioning of circadian controls may be involved in the etiology of the illness. Nocturnal light exposure, unusual timing of food, irregular sleep/wake schedules and traveling between different time zones are some of the factors responsible for improper entrainment of the clock. Recent reports have proposed that strengthening of circadian clock functioning and proper timing of food intake could stabilize glucose homeostasis. This strategy thus represents a chronotherapeutic option for non-pharmaceutical intervention in treating T2DM patients.


Assuntos
Ritmo Circadiano , Diabetes Mellitus Tipo 2 , Metabolismo Energético , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/prevenção & controle , Homeostase , Humanos
14.
Adv Pharmacol Sci ; 2014: 532969, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24790596

RESUMO

Several experimental and clinical reports indicated the oxidative stress-mediated adverse changes in vital organs of human and animal in fluoride (F) toxicity. Therefore, the present study was undertaken to evaluate the therapeutic effect of buffalo (Bubalus bubalis) epiphyseal (pineal) proteins (BEP) and melatonin (MEL) against F-induced oxidative stress in heart, liver, and kidney of experimental adult female rats. To accomplish this experimental objective, twenty-four adult female Wistar rats (123-143 g body weights) were divided into four groups, namely, control, F, F + BEP, and F + MEL and were administered sodium fluoride (NaF, 150 ppm elemental F in drinking water), MEL (10 mg/kg BW, i.p.), and BEP (100 µg/kg BW, i.p.) for 28 days. There were significantly (P < 0.05) high levels of lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase, glutathione reductase, and glutathione peroxidase in cardiac, hepatic, and renal tissues of F-treated rats. Administration of BEP and MEL in F-treated rats, however, significantly (P < 0.05) attenuated these adverse changes in all the target components of antioxidant defense system of cardiac, hepatic, and renal tissues. The present data suggest that F can induce oxidative stress in liver, heart, and kidney of female rats which may be a mechanism in F toxicity and these adverse effects can be ameliorated by buffalo (Bubalus bubalis) epiphyseal proteins and melatonin by upregulation of antioxidant defense system of heart, liver, and kidney of rats.

15.
Artigo em Inglês | MEDLINE | ID: mdl-23318689

RESUMO

Sleep-onset and maintenance insomnia is a common symptom in schizophrenic patients regardless of either their medication status (drug-naive or previously treated) or the phase of the clinical course (acute or chronic). Regarding sleep architecture, the majority of studies indicate that non-rapid eye movement (NREM), N3 sleep and REM sleep onset latency are reduced in schizophrenia, whereas REM sleep duration tends to remain unchanged. Many of these sleep disturbances in schizophrenia appear to be caused by abnormalities of the circadian system as indicated by misalignments of the endogenous circadian cycle and the sleep-wake cycle. Circadian disruption, sleep onset insomnia and difficulties in maintaining sleep in schizophrenic patients could be partly related to a presumed hyperactivity of the dopaminergic system and dysfunction of the GABAergic system, both associated with core features of schizophrenia and with signaling in sleep and wake promoting brain regions. Since multiple neurotransmitter systems within the CNS can be implicated in sleep disturbances in schizophrenia, the characterization of the neurotransmitter systems involved remains a challenging dilemma.


Assuntos
Ritmo Circadiano/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Transtornos do Sono-Vigília/etiologia , Sono/fisiologia , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Doença Crônica , Humanos , Melatonina/análogos & derivados , Melatonina/uso terapêutico , Esquizofrenia/complicações , Transtornos do Sono-Vigília/tratamento farmacológico
16.
Neurotox Res ; 23(3): 267-300, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22739839

RESUMO

The pineal product melatonin has remarkable antioxidant properties. It is secreted during darkness and plays a key role in various physiological responses including regulation of circadian rhythms, sleep homeostasis, retinal neuromodulation, and vasomotor responses. It scavenges hydroxyl, carbonate, and various organic radicals as well as a number of reactive nitrogen species. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and glutathione reductase, and by augmenting glutathione levels. Melatonin preserves mitochondrial homeostasis, reduces free radical generation and protects mitochondrial ATP synthesis by stimulating Complexes I and IV activities. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases. The efficacy of melatonin in preventing oxidative damage in either cultured neuronal cells or in the brains of animals treated with various neurotoxic agents, suggests that melatonin has a potential therapeutic value as a neuroprotective drug in treatment of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and brain trauma. Therapeutic trials with melatonin indicate that it has a potential therapeutic value as a neuroprotective drug in treatment of AD, ALS, and HD. In the case of other neurological conditions, like PD, the evidence is less compelling. Melatonin's efficacy in combating free radical damage in the brain suggests that it can be a valuable therapeutic agent in the treatment of cerebral edema following traumatic brain injury or stroke. Clinical trials employing melatonin doses in the range of 50-100 mg/day are warranted before its relative merits as a neuroprotective agent is definitively established.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/uso terapêutico , Melatonina/fisiologia , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Ritmo Circadiano/fisiologia , Ensaios Clínicos como Assunto , Método Duplo-Cego , Avaliação Pré-Clínica de Medicamentos , Radicais Livres/metabolismo , Homeostase/fisiologia , Humanos , Luz , Melatonina/agonistas , Melatonina/farmacologia , Melatonina/uso terapêutico , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Estudos Multicêntricos como Assunto , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/fisiologia , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Glândula Pineal/metabolismo , Glândula Pineal/efeitos da radiação , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Triptofano/metabolismo
17.
J. physiol. biochem ; 68(2): 237-245, jun. 2012.
Artigo em Espanhol | IBECS | ID: ibc-122343

RESUMO

In view of the significant health impact of oxidative stress and apoptosis dysfunction, and further, because of suggestions that administration of antioxidants might reduce apoptosis rate through up-regulation of body antioxidant defense systems, therefore the purpose of this study was to compare the effect of buffalo (Bubalus bubalis) pineal proteins (PP at 100 ìg/kg BW, i.p.) with melatonin (MEL at 10 mg/kg BW, i.p.) on blood (erythrocytes) antioxidant defense system and apoptosis in isolated peripheral blood lymphocytes of female Wistar albino rats. The cell viability index (%) and apoptosis index (%), which are directly related to the apoptosis rate of the cells, were used as dependent measures for inferring PP and MEL activity. The total cell viability index did not differ between rats treated with MEL and PP from control animals. The percentage of apoptotic cell death through fluorescence microscopy also did not change in MEL and PP groups as compared with control. DNA fragmentation as an index of apoptosis was detected with propidium iodide staining and assessed by flow cytometry. Pineal proteins and MEL administration caused significant (p < 0.05) reduction in lipid peroxidation and increased level of catalase, superoxide dismutase, glutathione peroxidase, and glutathione in erythrocytes as compared with control. Interestingly, we did not observe increase in the non-viable cells and percentage of apoptotic cell death in PP-treated group, controls or in animals in which MEL had been administered. Therefore, the present study confirmed the up-regulation of erythrocytes (blood) antioxidant defense systems and absence of adverse effect on rate of apoptosis in PP and MEL-administered rats under absence of stress or toxicant exposure. Hence, these test agents can be tested for further therapeutic values against adverse apoptosis rate under stress or toxicants exposures (AU)


Assuntos
Animais , Ratos , Melatonina/farmacocinética , Apoptose/fisiologia , Antioxidantes/fisiologia , Hormônios Neuro-Hipofisários/farmacocinética , Elementos de Resposta Antioxidante/fisiologia , Substâncias Protetoras/farmacocinética , Modelos Animais de Doenças , 5-Metoxitriptamina/farmacocinética
18.
CNS Neurol Disord Drug Targets ; 11(2): 180-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22483286

RESUMO

Insomnia is common among elderly people and nearly 30 to 40% of the adult population also suffer from insomnia. Pharmacological treatment of insomnia include the use of benzodiazepine and non-benzodiazepine drugs like zolpidem, zaleplon, Zopiclone. Although these drugs improve sleep, their usage is also associated with number of adverse effects, Melatonin, the hormone secreted by the pineal gland of all animals and human beings has been used for treatment of insomnias, since the timing of its secretion in humans as well as in most of the animals coincides with the increase of nocturnal sleep propensity. Because of its short half life, melatonin slow release preparations were introduced for treatment of insomnia. Recently ramelteon, a selective MT1, MT2 receptor agonist with greater efficacy of action in treating insomnia has been used clinically and has been found effective in improving sleep quality, sleep efficacy and also in reducing the sleep onset time when compared to melatonin or slow melatonin preparations. The mechanism of action of ramelteon in improving sleep is discussed in the paper. Another melatonergic drug agomelatine besides acting on MT1/MT2 receptors also displays 5-HT2c antagonism and this drug has been found effective as a novel antidepressant for treating major depressive disorders. Agomelatine besides causing remission of depressive symptoms also improves sleep quality and efficiency. Other antidepressants depressants that are in clinical use today do not improve sleep. There are other melatonergic drugs like tasimelteon, 6-chloromelatonin. But ramelteon and agomelatine deserve special attention for treatment of insomnia and sleep disturbances associated with depressive disorders and have promising role for treatment of sleep disorders.


Assuntos
Melatonina/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Animais , Depressores do Sistema Nervoso Central/uso terapêutico , Humanos , Indenos/química , Indenos/uso terapêutico , Melatonina/efeitos adversos , Melatonina/química
19.
J Physiol Biochem ; 68(2): 237-45, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22205582

RESUMO

In view of the significant health impact of oxidative stress and apoptosis dysfunction, and further, because of suggestions that administration of antioxidants might reduce apoptosis rate through up-regulation of body antioxidant defense systems, therefore the purpose of this study was to compare the effect of buffalo (Bubalus bubalis) pineal proteins (PP at 100 µg/kg BW, i.p.) with melatonin (MEL at 10 mg/kg BW, i.p.) on blood (erythrocytes) antioxidant defense system and apoptosis in isolated peripheral blood lymphocytes of female Wistar albino rats. The cell viability index (%) and apoptosis index (%), which are directly related to the apoptosis rate of the cells, were used as dependent measures for inferring PP and MEL activity. The total cell viability index did not differ between rats treated with MEL and PP from control animals. The percentage of apoptotic cell death through fluorescence microscopy also did not change in MEL and PP groups as compared with control. DNA fragmentation as an index of apoptosis was detected with propidium iodide staining and assessed by flow cytometry. Pineal proteins and MEL administration caused significant (p < 0.05) reduction in lipid peroxidation and increased level of catalase, superoxide dismutase, glutathione peroxidase, and glutathione in erythrocytes as compared with control. Interestingly, we did not observe increase in the non-viable cells and percentage of apoptotic cell death in PP-treated group, controls or in animals in which MEL had been administered. Therefore, the present study confirmed the up-regulation of erythrocytes (blood) antioxidant defense systems and absence of adverse effect on rate of apoptosis in PP and MEL-administered rats under absence of stress or toxicant exposure. Hence, these test agents can be tested for further therapeutic values against adverse apoptosis rate under stress or toxicants exposures.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linfócitos/metabolismo , Melatonina/farmacologia , Neuropeptídeos/farmacologia , Glândula Pineal/química , Animais , Antioxidantes/fisiologia , Búfalos , Catalase/sangue , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/enzimologia , Eritrócitos/metabolismo , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Peroxidação de Lipídeos , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Melatonina/fisiologia , Neuropeptídeos/fisiologia , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/sangue
20.
J Pineal Res ; 52(4): 365-75, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21951153

RESUMO

Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.


Assuntos
Depressão/tratamento farmacológico , Melatonina/análogos & derivados , Melatonina/agonistas , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Acetamidas/farmacologia , Animais , Depressão/metabolismo , Humanos , Hipnóticos e Sedativos/farmacologia , Indenos/farmacologia , Camundongos , Distúrbios do Início e da Manutenção do Sono/metabolismo
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