ChronoPhysiology and Therapy最新文献

{"title":"New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin","authors":"D. Cardinali, M. F. Vidal, D. Vigo","doi":"10.2147/CPT.S15514","DOIUrl":"https://doi.org/10.2147/CPT.S15514","url":null,"abstract":"A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT 1 and MT 2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used). 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. A prolonged-release preparation of mela- tonin 2 mg (Circadin ® ) has been approved for the treatment of primary insomnia in patients aged $55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo, and was associated with significantly less impairment on many of these tasks relative to zolpidem alone or in combination with prolonged-release melatonin. In 3-week and 6-month randomized, double-blind, clinical trials in patients with primary insomnia aged $55 years, prolonged-release melatonin was associated with improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness, and quality of life. Prolonged-release melatonin was very well tolerated in clinical trials in older patients, with a tolerability profile similar to that of placebo. Short-term or longer- term treatment with prolonged-release melatonin was not associated with dependence, tolerance, rebound insomnia, or withdrawal symptoms.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78024133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature biofeedback and sleep: limited findings and methodological challenges","authors":"G. Forest, C. Heuvel, K. Lushington, J. Koninck","doi":"10.2147/CPT.S33147","DOIUrl":"https://doi.org/10.2147/CPT.S33147","url":null,"abstract":"Given the close link between body temperature and sleep, the perspective of manipu- lating core and peripheral temperature by self-regulation techniques is very appealing. We report here on a series of attempts conducted independently in two laboratories to use self-regulation (biofeedback) of oral (central) and hand (peripheral) temperature, and measured the impact on sleep-onset latency, sleep architecture, and circadian phase. We found that hand temperature was more successful than oral temperature biofeedback. Moreover, an increase in hand tem- perature was associated with reduced sleep-onset latency. However, most participants found the procedure difficult to implement. The temperature response to biofeedback was reduced in the aged and weakest at the time of sleep onset, and there was not a systematic relationship between the change in temperature and change in sleep latency. Methodological limitations and individual differences may account for these results. Recommendations for future research are presented.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91156812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute myocardial infarction and infarct size: do circadian variations play a role?","authors":"Aida Suárez-Barrientos, B. Ibáñez","doi":"10.2147/CPT.S22581","DOIUrl":"https://doi.org/10.2147/CPT.S22581","url":null,"abstract":"The circadian rhythm influences cardiovascular system physiology, inducing diurnal variations in blood pressure, heart rate, cardiac output, endothelial functions, platelet aggregation, and coronary arterial flow, among other physiological parameters. Indeed, an internal circadian network modulates cardiovascular physiology by regulating heart rate, metabolism, and even myocyte growth and repair ability. Consequently, cardiovascular pathology is also controlled by circadian oscillations, with increased morning incidence of cardiovascular events. The potential circadian influence on the human tolerance to ischemia/reperfusion has not been systematically scrutinized until recently. It has since been proven, in both animals and humans, that infarct size varies during the day depending on the symptom onset time, while circadian fluctuations in spontaneous cardioprotection in humans with ST-segment elevation myocardial infarction (STEMI) have also been demonstrated. Furthermore, several studies have proposed that the time of day at which revascularization occurs in patients with STEMI may also influence infarct size and reperfusion outcomes. The potential association of the circadian clock with infarct size advocates the acknowledgment of time of day as a new prognostic factor in patients suffering acute myocardial infarction, which would open up a new field for chronotherapeutic targets and lead to the inclusion of time of day as a variable in clinical trials that test novel","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75810622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and optimization of chronomodulated press-coated tablet of carvedilol by Box–Behnken statistical design","authors":"Rohan S Satwara, P. Patel","doi":"10.2147/CPT.S34930","DOIUrl":"https://doi.org/10.2147/CPT.S34930","url":null,"abstract":"Objective: The primary objective of the present investigation was to formulate and optimize chronomodulated press-coated tablets to deliver the antihypertensive carvedilol at an effective quantity predawn, when a blood pressure spike is typically observed in most hypertensive patients. Experimental work: Preformulation studies and drug excipient compatibility studies were carried out for carvedilol and excipients. Core tablets (6 mm) containing carvedilol and 10-mm press-coated tablets were prepared by direct compression. The Box–Behnken experimental design was applied to these press-coated tablets (F1–F15 formula) with differing concentrations of rate-controlling polymers. Hydroxypropyl methyl cellulose K4M, ethyl cellulose, and K-carrageenan were used as rate-controlling polymers in the outer layer. These tablets were subjected to various precompression and postcompression tests. The optimized batch was derived both by statistically (using desirability function) and graphically (using Design Expert ® 8; Stat-Ease Inc). Tablets formulated using the optimized formulas were then evaluated for lag time and in vitro dissolution. Results and discussion: Results of preformulation studies were satisfactory. No interaction was observed between carvedilol and excipients by ultraviolet, Fourier transform infrared spectroscopy, and dynamic light scattering analysis. The results of precompression studies and postcompression studies were within limits. The varying lag time and percent cumulative carvedilol release after 8 h was optimized to obtain a formulation that offered a release profile with 6 h lag time, followed by complete carvedilol release after 8 h. The results showed no significant bias between predicted response and actual response for the optimized formula. Conclusion: Bedtime dosing of chronomodulated press-coated tablets may offer a promising alternative to control early morning hypertensive increase. swelling and erosion of the outer coat until the desired lag time has been achieved. 15–18 The ratio of hydrophilic polymers that affects the lag time, ie, the amount of HPMC K4M, EC, and K-carrageenan in the outer layer, were selected based on screening experiments. This ratio was confirmed using computer-aided optimization using a three factors, three-level, Box–Behnken experiment design (BBD) with constraints on lag time and percent cumulative carvedilol release after 8 h.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82071651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of biological rhythms in drug treatment of hypertension and sex-dependent modifications","authors":"B. Lemmer","doi":"10.2147/CPT.S21861","DOIUrl":"https://doi.org/10.2147/CPT.S21861","url":null,"abstract":"The cardiovascular system is highly organized in time. Blood pressure, heart rate, peripheral resistance, pressure, and vasodilating hormones display pronounced circadian variations. New data presented here demonstrate also sex-dependent differences in vasodilating hormones, with higher NO χ excretion in females than males and a steeper early morning rise in norepinephrine in males, whereas the 24-hour blood pressure and heart-rate profiles were not different. Various antihypertensive drugs were investigated in crossover studies - morning versus evening dosing - in hypertensive patients; however, consistent data were only described for angiotensin-converting-enzyme (ACE) inhibitors, calcium channel blockers, and angiotensin II type 1 (AT 1 ) receptor blockers. Whereas in dippers ACE inhibitors had a superdipping effect when dosed at night, no difference in the blood pressure lowering effect or on the 24-hour blood pressure profile was found with calcium channel blockers after morning and evening dosing. In nondippers, the calcium channel blockers isradipine and amlodipine transformed nondippers into dippers, similar after evening dosing. The effects of AT 1 -receptor blockers are similar to those of ACE inhibitors. Also, diuretics are able to normalize non dipping behavior. Moreover, a circadian phase dependency in their pharmacokinetics has been demonstrated for various cardiovascular-active drugs, such as beta blockers, calcium channel blockers, oral nitrates, and ACE inhibitors, modified by the galenic formulation. There is evidence that in hyperten- sive dippers, antihypertensive drugs should be given during early morning hours, whereas in non dippers it can be necessary to add an evening dose or even to apply a single evening dose in order not only to reduce high blood pressure, but also to normalize a disturbed non dipping 24-hour blood pressure profile.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84793740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular clock: a focus on chronopharmacological strategies for a possible control of aminoglycoside renal toxicity","authors":"M. Rebuelto","doi":"10.2147/CPT.S21855","DOIUrl":"https://doi.org/10.2147/CPT.S21855","url":null,"abstract":"Chronotherapy applies biological rhythmicity in order to optimize clinical treatments, relating the dosing time of the drugs to the daily variations of their therapeutic and unwanted side effects due to the fluctuations in physiological processes involved in their pharmacokinetics and/or pharmacodynamics. The goal of chronotherapy is to administer treatments at the time of day that enhances both their effectiveness and tolerance. This review intends to (1) provide the theoretical rationale behind the use of aminoglycosides during extended interval schedule chronotherapy in clinical practice and (2) target the underlying molecular mechanisms of renal toxicity, the main unwanted side effect. Previous reports suggest that aminoglycoside therapy may benefit from a chronopharmacological approach. Temporal variations in the renal blood flow and glomerular filtration rate and several clock-dependent molecular mechanisms contributing to the daily changes in electrolyte and water urinary excretion have been reported. Daily differences in aminoglycoside toxicity and kinetic disposition have been found in laboratory animals and human patients. Nephrotoxicity and renal cortical accumulation are higher when drugs are administered during the rest phase than during the active phase. Active translocation of aminoglycosides into renal cells is mediated by the megalin/cubilin receptor complex located at the luminal epithelial cell membrane. The complex regulation of this endocytic mechanism deserves further study, in order to dilucidate the molecular bases that may be involved in chrono- therapeutic strategies developed for minimizing aminoglycoside accumulation in the renal cells, and thus, increasing their tolerance.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89025766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The melatonergic system: effects on sleep and implications for the treatment of psychiatric disorders","authors":"D. D. Berardis, T. Acciavatti, G. Iorio, M. Corbo, N. Serroni, D. Campanella, Fabiola Di Emidio, M. Piersanti, M. Cavuto, G. Martinotti, Francesco Saverio, Moschetta, M. Giannantonio","doi":"10.2147/CPT.S16972","DOIUrl":"https://doi.org/10.2147/CPT.S16972","url":null,"abstract":"Correspondence: Domenico De Berardis National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, “G. Mazzini” Hospital, p.zza Aldo Moro 1, 64100 Teramo, italy Tel +39 0861429708 Fax +39 0861429706 email dodebera@aliceposta.it Abstract: The circadian pacemaker or biological clock, located in the hypothalamic suprachiasmatic nucleus, is the generation site of circadian rhythms. The light/dark cycle is the circadian pacemaker’s dominant synchronizing agent, though it is also influenced by neurotransmitters and the phase-shifting effects of various chemical and pharmacological components, of which melatonin (N-acetyl-5-methoxytryptamine) is the most well established. In recent years, melatonin and melatonin analogs have been commercialized in many countries, mainly with hypnotic purposes. A new compound, agomelatine, has been recently synthesized and studied. Among melatonin analogs, this drug possesses unique pharmacological and clinical features; it is an antagonist at 5-HT2B and 5-HT2C receptors and has well established antidepressant and anxiolytic properties. Agomelatine opens new perspectives in the chronobiotic treatment of depression. The purpose of the present review was to elucidate the effects of the melatonergic system on sleep and the implications for the treatment of psychiatric disorders.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89968889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OSA – a risk factor for stroke","authors":"C. Ryan","doi":"10.2147/CPT.S16490","DOIUrl":"https://doi.org/10.2147/CPT.S16490","url":null,"abstract":"Obstructive sleep apnea is a sleep breathing disorder characterized by recurrent and intermittent hypoxia with continued respiratory effort against a closed glottis. The result of this is a cascade of acute and chronic systemic pathophysiological responses that cause endothelial dysfunction, atherosclerosis and lead to cardiovascular and cerebrovascular disease. This article focuses on the clinical evidence linking obstructive sleep apnea and stroke and on the specific mechanisms perpetuating stroke risk in this population.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86216675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of obstructive sleep apnea on blood pressure in patients with hypertension","authors":"Barry G. Fields, I. Gurubhagavatula","doi":"10.2147/CPT.S16487","DOIUrl":"https://doi.org/10.2147/CPT.S16487","url":null,"abstract":"Correspondence: Barry Fields Division of Sleep Medicine, 3624 Market Street, Suite 205, Philadelphia, PA 19104, USA Tel +1 215-615-4875 Fax +1 215-615-4874 email barry.fields@uphs.upenn.edu Abstract: Hypertension is the most significant risk factor for death worldwide. Approximately 30%–40% of affected individuals have coexisting obstructive sleep apnea (OSA), a disorder resulting from the upper airway’s inability to remain patent during sleep. A causal relationship between OSA and hypertension has been demonstrated. Blunting or elimination of normal blood pressure (BP) dipping during sleep is commonly seen in OSA patients, with corresponding increases in daytime BP. This dipping is clinically salient, because it is associated with the endorgan damage seen with chronic hypertension, such as cardiovascular, renal, and cerebrovascular disease. African-Americans are at greatest risk for non-dipping and end-organ damage. Rapidly fluctuating changes in sympathetic tone, intrathoracic pressure, oxyhemoglobin saturation, and carbon dioxide levels are all thought to play a role in acute and chronic BP elevation. Individuals with preexisting hypertension are most susceptible to OSA’s BP-raising effects. First-line therapy for OSA includes continuous positive airway pressure (CPAP) delivered via a mask interface. Patients who show the greatest BP declines while using CPAP are more likely to be those who have at least moderate OSA, adhere to therapy, have preexisting hypertension, and whose blood vessels retain reversibility in disease-related remodeling. Given the heavy burden OSA-related hypertension places on the healthcare system, prevention, early detection, and prompt intervention should be the goals for all affected individuals.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84172522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian variations in blood pressure in health and disease: implications for patient management","authors":"A. Chugh, J. Loughran, M. Slaughter","doi":"10.2147/CPT.S15597","DOIUrl":"https://doi.org/10.2147/CPT.S15597","url":null,"abstract":"Traditionally, blood pressure measurements have been performed in office settings and have provided the basis for all diagnostic and therapeutic decisions. However, the develop- ment of a clinically relevant 24-hour blood pressure monitoring system has added greatly to the ability of blood pressure values to confer additional clinical information, including prognostic value. Mechanistically, the circadian rhythm of blood pressure is mediated by a complex pro- cess as a part of the neurohormonal cascade. Pattern recognition of blood pressure peaks and troughs over a 24-hour period has led to categorization into specific subsets namely, ie, dip- pers, nondippers, extreme dippers, and reverse dippers. Cardiovascular risk is associated with certain pattern types, as has been demonstrated in large observational and prospective studies. The development of therapies for the purpose of restoring more pathological patterns to normal ones continues to grow. These include both pharmaceutical and device therapy. This article describes the development of 24-hour blood pressure monitoring systems, the identification of circadian blood pressure patterns, and the treatment strategies studied thus far which affect these newer blood pressure parameters.","PeriodicalId":10315,"journal":{"name":"ChronoPhysiology and Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90655917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}