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Sleep deprivation therapy: A rapid-acting antidepressant
Published in S.R. Pandi-Perumal, Meera Narasimhan, Milton Kramer, Sleep and Psychosomatic Medicine, 2017
We hypothesize that a subgroup of depressed patients with abnormal circadian rhythms may have a state-related defect in clock gene machinery. With remission, many of the dysregulated rhythms normalize. Figure 20.2 illustrates that chronotherapeutic interventions such as SDT, bright light therapy, and sleep phase advance may act, in part, by resetting and stabilizing circadian function. Clinical relapse may reflect a desynchronization in circadian function associated with the reactivation of abnormal clock gene expression.
The Pineal Gland Energy Transducer
Published in Len Wisneski, The Scientific Basis of Integrative Health, 2017
Similarly, the progression of disease and the intensity of side effects for patients with colorectal cancer are enormously influenced by the time of day that chemotherapeutic drugs are administered and their correlation to concurrent radiation therapy (Bressolle et al., 1999; Hrushesky, 1985, 2001; Peters et al., 1987; Thrall et al., 2000). Regrettably, these factors have been brought to the attention of few physicians in the United States. Research stemming from a laboratory in Villejuif, France, has actually shown that lack of a distinct circadian rest–activity rhythm in cancer patients is a novel independent prognostic factor for survival (Levi, 2000; Mormont et al., 2000). The researchers encourage chronotherapeutic adjustments as part of these patients' overall cancer treatment (i.e., protocols designed to adjust their circadian rhythms more in line with usual patterns and with normal levels of melatonin expression).
Modified-Release Delivery Systems
Published in Larry L. Augsburger, Stephen W. Hoag, Pharmaceutical Dosage Forms, 2017
Multiple delivery systems with potential use in chronotherapeutics in concord with the circadian rhythms of the disease have been developed with specific time-dependent “trigger” mechanisms for delivery of drug at a particular rate to a specific region of the GI tract. One such delivery system is Pulsincap,40,41 which consists of an insoluble and impermeable capsule body and a water-soluble cap with possibility for pH-sensitive coating as graphically shown in Figure 12.23. The capsule cap is soluble in water or a desired pH environment while the capsule body is impermeable to water. Drug and swelling polymer can be used as part of drug formulation together or independent of each other and filled into the body of the capsule. A swelling and eroding hydrogel plug or an eroding compressed tablet is used to seal the content. Upon oral administration, the cap will dissolve in the specific pH environment followed by gradual but controlled hydration, swelling, and erosion of the plug. Compositionally, the plug is made of a swellable, erodible (e.g., HPMC, soluble polymethacrylate, polyvinyl alcohol), or congealed melted excipient (e.g., glyceryl monooleate), or an enzymatically degradable polysaccharide like pectin. Once the plug is dissolved, fluid gradually enters the capsule body from the open end. For rapid release of insoluble drugs, a disintegrant or an effervescent agent may be added to the formulation. The expulsion agent also swells and expands and the drug formulation is expelled for complete dissolution. The second-generation Pulsincap has been further optimized for a more predictable and accurate plug ejection and composition of the expulsion agent to rapidly and completely expel the contents. The system has been used in several human studies demonstrating that the system was well tolerated in the volunteers as well as in the clinic, and its performance and location within the GI tract are monitored using scintigraphy studies.
Exploration of polymethacrylate and Hypromellose for the development of a non-sulfhydryl ACE inhibitor mucoadhesive system using Box-Behnken design: in-vitro and ex-vivo evaluation
Published in Drug Development and Industrial Pharmacy, 2023
According to the World Health Organization, hypertension, often known as high blood pressure, is a serious medical condition that raises the risk of heart, kidney, and other ailments as well as brain and other diseases [1]. In 2021, a total of 1.28 billion adults (30–79 years) equal to 46% of the world population estimated to have hypertension, mostly from developing or underdeveloped countries [2]. As per WHO, out of total high blood pressure individuals, approximately 42% of them were diagnosed and treated [3–5]. Additionally, most anti-hypertensive drugs have been administered in the morning but the intensity of symptoms varies with an individual’s circadian rhythm and the drug should be present within the therapeutic level during that duration[6]. The chronotherapeutic approach to drug administration increases patient compliance and minimizes side effects [7]. As per the US FDA trough-peak ratio between 50-100% is a prerequisite for a once-a-day drug delivery system and Perindopril Erbumine (PER) has a 75% trough-peak ratio which makes it suitable for a once-a-day drug delivery system [8–11]. It is a non-sulfhydryl ACE inhibitor and prevents the transformation of angiotensin I into angiotensin II [12]. Among all ACE inhibitors, PER causes minimum first-dose hypotension [13].
Circadian rhythms of risk factors and management in atherosclerotic and hypertensive vascular disease: Modern chronobiological perspectives of an ancient disease
Published in Chronobiology International, 2023
Yong-Jian Geng, Michael H. Smolensky, Oliver Sum-Ping, Ramon Hermida, Richard J. Castriotta
Many molecular oscillators or clock gene products or proteins have been identified in the mammalian circadian system that play a critical role in the generation and maintenance of cell-autonomous rhythms (Dibner et al. 2010). For instance, the Circadian Locomotor Output Cycle Kaput (CLOCK) and Brain Muscle Aryl Hydrocarbon Receptor Nuclear Translocator-Like 1 (BMAL1, encoded by the ARNTL gene) are two clock proteins that act as primary regulators of circadian rhythms. In this review, we will update the progress of circadian gene research related to atherosclerosis, hypertension and other metabolic disorders. Finally, we will summarize recent data from several clinical studies using chronotherapeutic approaches that demonstrate progress in the mitigation of risk for morbid and mortal cardiac and vascular outcomes.
Valsartan-mediated chronotherapy in spontaneously hypertensive rats via targeting clock gene expression in vascular smooth muscle cells
Published in Archives of Physiology and Biochemistry, 2022
Jiajie Luan, Kui Yang, Yanyun Ding, Xiaotong Zhang, Yaqin Wang, Haiju Cui, Deixi Zhou, Lu Chen, Zhangqing Ma, Wusan Wang, Wen Zhang, Xiaoyun Liu
Chronotherapeutic strategies represent an emerging therapeutic approach that has been developed and validated to be beneficial (through clinical experience and/or trials) for modulating/correcting circadian disruptions and/or associated symptoms of several diseases, including hypertension (Smolensky et al. 2016). Numerous studies suggest that direct and/or indirect targeting of circadian clock components may counteract the disruptive effects of some drugs via resetting circadian rhythms to a specific phase and/or by enhancing their amplitudes (Smolensky et al. 2016, Sulli et al. 2018). Therefore, an improved mechanistic understanding of the cell-autonomous molecular circadian oscillator and the entire circadian timing system has enabled new conceptual and methodological lines of investigation to better understand the impact of this system and its components on a specific drug’s daily variations or the effects/side effects of environmental substances (Dallmann et al. 2016).