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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol and caffeine are two of the oldest human drugs. Their pervasive integration into the modern human diet may reflect behavioral attempts to correct maladaptations induced by evolutionary displacement of the autonomic system. The dietary adoption of caffeine may parallel the emergence of cognition as an independent basis of competition. Enhancement of the cognitive ability to gather and process information likely evolved as a valuable adjunct to physical behavior in prehistoric fight-or-flight encounters. Caffeine effectively exploits this pre-existing association between adrenergic activity and cognitive readiness, leading to its use in the modern environment where success in competition increasingly depends on cognitive, rather than physical, prowess. Ethanol may have emerged as a dietary means to buffer the maladaptive chronic sympathetic activation and fear response associated with stressful lifestyles and the social phobias associated with the dissolution of kin networks. We explore the health implications of ethanol and caffeine use, with particular attention to their acute and chronic effects on the autonomic axis. The putative protective effects of ethanol in surviving major trauma or reducing inflammation and heart disease may relate to tempering the behavioral and cardiovascular consequences of catastrophic or chronic sympathetic activation. Acute or chronic abuse of ethanol manifests paradoxical pro-adrenergic effects such as tremors and insomnia that may partly represent compensatory responses. Compensatory remodeling may also explain why confirmation of detrimental effects related to caffeine-induced sympathetic activation has proven elusive; indeed, paradoxical pro-vagal benefits may eventually be recognized. Ethanol and caffeine are potential agents that may beneficially expand the dynamic range of the autonomic system. In an environment where the Darwinian value of knowledge has increasingly supplanted that of physical traits, the consumption of caffeine and alcohol may represent both a cause and an effect of modern human evolution.
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PMID:Brewing controversies: Darwinian perspective on the adaptive and maladaptive effects of caffeine and ethanol as dietary autonomic modulators. 1719 16

It is imperative that primary care clinicians have a thorough understanding of insomnia, because they are often the first point of contact for patients who seek assistance when they have difficulty sleeping. Insomnia may appear with different presentations: sleep onset, sleep maintenances, sleep offset, nonrestorative sleep, or a combination of these symptoms. Untreated symptoms result in clinically significant distress or impairment in social, occupational, or other important areas of following-day functionality. Physicians, pharmacists, and other clinicians should be aware of the conditions that contribute to, are antecedent to, and associated with insomnia. These pathophysiological conditions include advanced age; female gender; respiratory, gastrointestinal, vascular, and rheumatologic pain syndromes; and other conditions such as depression and/or anxiety. Additional health factors contributing to insomnia include chronic pain, stressors, grief reaction, pharmacotherapeutic side effects, lifestyle contributors such as social/recreational drugs, phytopharmaceuticals, and ethanol use. The pharmacotherapy focus in this article is a modified-release formulation of the BZ1 (omega1) receptor agonist zolpidem, zolpidem extended-release. Pharmacokinetic, pharmacodynamic, and safety studies that compare 12.5 mg zolpidem extended-release (Ambien CRtrade markCIV) and 10 mg original zolpidem were initially conducted in healthy volunteers to assess the potential for an improved clinical profile. Zolpidem extended-release (12.5 mg and 6.25 mg extended-release dosage forms) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Zolpidem extended-release is devoid of any short-term use limitation and can be prescribed for the duration of medical necessity. The modified-release zolpidem is a two-layer tablet with a biphasic release profile, releasing the first layer immediately, whereas the second layer is released at a slower rate. Plasma concentrations are maintained for a longer period of time versus the immediate-release zolpidem formulation. Pharmacokinetic analysis has also demonstrated that the time to maximum concentration (tmax) and terminal elimination half-life (t1/2) of 12.5 mg zolpidem extended-release are similar to those of 10 mg zolpidem indicating a similar rapid onset of action and an elimination profile that reduced the risk of next-day decrements in performance. Zolpidem's CYP 450 hepatic metabolism uses as a substrate CYP3A4 (major) and 1A2, 2C9, 2C19, and 2D6 as minor pathways. Zolpidem extended-release dosage forms diminish sleep latency, number of awakenings, and wakefulness after sleep onset and augments total time asleep.
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PMID:Zolpidem extended-release: a single insomnia treatment option for sleep induction and sleep maintenance symptoms. 1751 7

Armillariella mellea (AM), also known as Mi-Huan-Ku, a popular medicinal fungus used in the traditional Chinese medicine for treating headache, neurasthenia and insomnia. In the present study, our aim was to determine the effects of aqueous (AAM) and ethanol (EAM) extracts of A. mellea on lipopolysaccharide (LPS)-induced inflammatory response by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1 and -2 (COX-1 and COX-2) protein expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin (PGE(2)) production in human monocytic (THP-1) cells. At concentration of 100 microg/ml, EAM, but not AAM, effectively protected against LPS-induced cell death in THP-1 cells. At concentrations of 10 approximately 100 microg/ml, EAM showed a potent anti-inflammatory activity as demonstrated by a dose-dependent inhibition of LPS (1 microg/ml)-induced release of NO and PGE(2), and significantly decreased the transcription of proinflammatory cytokines. EAM at 100 mug/ml significantly blocked the LPS induction of iNOS and COX-2 expression, but not COX-1. Therefore, the protective effect of EAM against LPS-induced inflammatory mediators release could explain, at least in part, its effectiveness in alleviating certain inflammatory related diseases.
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PMID:Armillariella mellea shows anti-inflammatory activity by inhibiting the expression of NO, iNOS, COX-2 and cytokines in THP-1 cells. 1759 9

Valerian (Valeriana Officinallis) is a perennial plant used as a mild sedative for anxiety and for insomnia. It is also used in the treatment of gastrointestinal cramps and as a diuretic. It is traditionally contraindicated in pregnancy; however, there are no studies to warrant this warning. This study was performed to provide some information to fill this knowledge gap. Female rats were orally dosed with a valerian extract in 45% ethanol (supplied by MediHerb) daily on either gestation days (GD) 1-8 or 8-15. On GD 20, rats were sacrificed and fetuses, placentae and ovaries collected. The fetuses were weighed and examined for external malformations. No signs of maternal toxicity were evident. Results indicated that valerian had no adverse effects on fertility or fetal development. Valerian induced toxicity when GD 10.5 embryos were cultured for 26h in rat serum to which 6 microl/ml of the extract was added. The results of the present preliminary study showed that consumption of up to 65 times the human dose of the valerian extract supplied by Mediherb did not have an adverse reproductive outcome in rats. This may be a result of low pH of the extract removing the potentially cytotoxic epoxide moieties. However, consumption of other preparations of valerian, particularly if they contained considerable levels of valepotriates could have a very different outcome.
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PMID:A developmental toxicity-screening test of valerian. 1761 Oct 59

(1) Circadian clocks have been localized to discrete sites within the nervous system of several organisms and in mammals to the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN controls and regulates the production and discharge of melatonin (hormonal message of darkness) from the pineal gland via a multisynaptic efferent pathway. The nocturnal rise in melatonin production from serotonin results due to an increased activity of serotonin N-acetyl transferase (NAT). (2) The complex interaction between alcohol and biological clock need to be understood as alcoholism results in various clock linked neuronal disorders especially loss of memory and amnesia like state of consciousness, sleep disorders, insomnia, dementia etc. (3) Serotonin, 5-Hydroxy-tryptamine (5-HT) plays an important role in mediating alcohol's effects on the brain. Understanding the impact of alcohol consumption on circadian system is a pre-requisite to help in treatment of alcohol induced neurological disorders. We, therefore, studied the effect of ethanol drinking and ethanol withdrawal on daily rhythms of serotonin and its metabolite, 5-hydroxy-indole acetic acid (5-HIAA) in SCN and Pineal of adult male Wistar rats maintained under light-dark (LD, 12:12) conditions. (4) Curcumin is well known for its protective properties such as antioxidant, anti-carcinogenic, anti-viral and anti-infectious etc. Hence, we studied the effect of curcumin on ethanol induced changes on 5-HT and 5-HIAA levels and rhythms in SCN and Pineal. (5) Ethanol withdrawal could not restore either rhythmicity or phases or levels of 5-HT and 5-HIAA. Curcumin administration resulted in partial restoration of daily 5-HT/5-HIAA ratio, with phase shifts in SCN and in Pineal. Understanding the impact of alcohol consumption on circadian system and the role of herbal medication on alcohol withdrawal will help in treatment of alcohol induced neurological disorders.
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PMID:The effect of curcumin on ethanol induced changes in suprachiasmatic nucleus (SCN) and pineal. 1784 84

The frequency of sleep disruption and the degree to which insomnia significantly affects daytime function determine the need for evaluation and treatment. Physicians may initiate treatment of insomnia at an initial visit; for patients with a clear acute stressor such as grief, no further evaluation may be indicated. However, if insomnia is severe or long-lasting, a thorough evaluation to uncover coexisting medical, neurologic, or psychiatric illness is warranted. Treatment should begin with nonpharmacologic therapy, addressing sleep hygiene issues and exercise. There is good evidence supporting the effectiveness of cognitive behavior therapy. Exercise improves sleep as effectively as benzodiazepines in some studies and, given its other health benefits, is recommended for patients with insomnia. Hypnotics generally should be prescribed for short periods only, with the frequency and duration of use customized to each patient's circumstances. Routine use of over-the-counter drugs containing antihistamines should be discouraged. Alcohol has the potential for abuse and should not be used as a sleep aid. Opiates are valuable in pain-associated insomnia. Benzodiazepines are most useful for short-term treatment; however, long-term use may lead to adverse effects and withdrawal phenomena. The better safety profile of the newer-generation nonbenzodiazepines (i.e., zolpidem, zaleplon, eszopidone, and ramelteon) makes them better first-line choices for long-term treatment of chronic insomnia.
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PMID:Treatment options for insomnia. 1785 25

Drinking alcohol is associated with the disturbance of normal sleep rhythms, and insomnia is a major factor in alcoholic relapse. The thalamus is a brain structure that plays a pivotal role in sleep regulation and rhythmicity. A number of studies have implicated GABA(A) receptors (GABA(A)-Rs) in the anxiolytic, amnestic, sedative, and anesthetic effects of ethanol. In the present study, we examined the effects of ethanol on both synaptic and extrasynaptic GABA(A)-Rs of relay neurons in the thalamus. We found that ethanol (> or =50 mM) elicits a sustained current in thalamocortical relay neurons from the mouse ventrobasal thalamus, and this current is associated with a decrease in neuronal excitability and firing rate in response to depolarization. The steady current induced by ethanol was totally abolished by gabazine and was absent in relay neurons from GABA(A)-R alpha(4) subunit knockout mice, indicating that the effect of ethanol is to enhance tonic GABA-mediated inhibition. Ethanol (50 mM) enhanced the amplitude of tonic inhibition by nearly 50%. On the other hand, ethanol had no effect on spontaneous or evoked inhibitory postsynaptic currents (IPSCs) at 50 mM but did prolong IPSCs at 100 mM. Ethanol had no effect on the paired-pulse depression ratio, suggesting that the release of GABA from presynaptic terminals is insensitive to ethanol. We conclude that ethanol, at moderate (50 mM) but not low (10 mM) concentrations, can inhibit thalamocortical relay neurons and that this occurs mainly via the actions of ethanol at extrasynaptic GABA(A)-Rs containing GABA(A)-R alpha(4) subunits.
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PMID:Ethanol modulates synaptic and extrasynaptic GABAA receptors in the thalamus. 1847 66

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.
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PMID:Anti-acetylcholinesterase activities of traditional Chinese medicine for treating Alzheimer's disease. 1857 42

Alcohol dependence and alcohol abuse or harmful use cause substantial morbidity and mortality. Alcohol-use disorders are associated with depressive episodes, severe anxiety, insomnia, suicide, and abuse of other drugs. Continued heavy alcohol use also shortens the onset of heart disease, stroke, cancers, and liver cirrhosis, by affecting the cardiovascular, gastrointestinal, and immune systems. Heavy drinking can also cause mild anterograde amnesias, temporary cognitive deficits, sleep problems, and peripheral neuropathy; cause gastrointestinal problems; decrease bone density and production of blood cells; and cause fetal alcohol syndrome. Alcohol-use disorders complicate assessment and treatment of other medical and psychiatric problems. Standard criteria for alcohol dependence-the more severe disorder-can be used to reliably identify people for whom drinking causes major physiological consequences and persistent impairment of quality of life and ability to function. Clinicians should routinely screen for alcohol disorders, using clinical interviews, questionnaires, blood tests, or a combination of these methods. Causes include environmental factors and specific genes that affect the risk of alcohol-use disorders, including genes for enzymes that metabolise alcohol, such as alcohol dehydrogenase and aldehyde dehydrogenase; those associated with disinhibition; and those that confer a low sensitivity to alcohol. Treatment can include motivational interviewing to help people to evaluate their situations, brief interventions to facilitate more healthy behaviours, detoxification to address withdrawal symptoms, cognitive-behavioural therapies to avoid relapses, and judicious use of drugs to diminish cravings or discourage relapses.
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PMID:Alcohol-use disorders. 1941 Jul 5

Insomnia afflicts many individuals, but particularly those in chronic methadone treatment. Studies examining sleep deprivation (SD) have begun to identify sleep restoration processes involving brain bioenergetics. The technique ([31])P magnetic resonance spectroscopy (MRS) can measure brain changes in the high-energy phosphates: alpha-, beta-, and gamma-nucleoside triphosphate (NTP). In the present study, 21 methadone-maintained (MM) and 16 control participants underwent baseline (BL), SD (40 wakeful hours), recovery1 (RE1), and recovery2 (RE2) study nights. Polysomnographic sleep was recorded each night and ([31])P MRS brain scanning conducted each morning using a 4T MR scanner (dual-tuned proton/phosphorus head-coil). Interestingly, increases in total sleep time (TST) and sleep efficiency index (SEI) commonly associated with RE sleep were not apparent in MM participants. Analysis of methadone treatment duration revealed that the lack of RE sleep increases in TST and SEI was primarily exhibited by short-term MM participants (methadone <12 months), while RE sleep in long-term MM (methadone >12 months) participants was more comparable to control participants. Slow wave sleep increased during RE1, but there was no difference between MM and control participants. Spectral power analysis revealed that compared to control participants; MM participants had greater delta, theta, and alpha spectral power during BL and RE sleep. ([31])P MRS revealed that elevations in brain beta-NTP (a direct measure of ATP) following RE sleep were greater in MM compared to control participants. Results suggest that differences in sleep and brain chemistry during RE in MM participants may be reflective of a disruption in homeostatic sleep function.
Drug Alcohol Depend 2010 Jan 15
PMID:Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: a [31]P MRS brain imaging study. 1977 35


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