Academia Mexicana de Medicina del Dormir A.C.

Difusión, intercambio científico e investigación en todas las áreas de la medicina del sueño

Artículos Científicos en texto completo


For their discoveries of molecular mechanisms controlling the circadian rhythm
The Nobel Assembly at Karolinska Institutet has today decided to award the 2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young.

Life on Earth is adapted to the rotation of our planet. For many years we have known that living organisms, including humans, have an internal, biological clock that helps them anticipate and adapt to the regular rhythm of the day. But how does this clock actually work? Jeffrey C. Hall, Michael Rosbash and Michael W. Young were able to peek inside our biological clock and elucidate its inner workings. Their discoveries explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions.
Using fruit flies as a model organism, this year’s Nobel laureates isolated a gene that controls the normal daily biological rhythm. They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. Subsequently, they identified additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell. We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.
With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day. The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism. Our wellbeing is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience “jet lag”. There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner timekeeper is associated with increased risk for various diseases.

 

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Fifty Years of Physiology in Obstructive Sleep Apnea. Magdy Younes, M.D., F.R.C.P.C., Ph.D.Department of Medicine University of Manitoba Winnipeg, Manitoba, Canada American Journal of Respiratory and Critical Care Medicine Volume 196 Number 8 | October 15 2017.

Before 1978, investigations focused on the obesity–hypoventilation syndrome, consisting of anecdotal reports of airway obstruction, with the most significant being a report by Gastaut and coworkers that described episodes of obstruction in one patient. Dramatic improvement after tracheostomy confirmed that obstruction was in the upper airway. In 1978, Remmers and colleagues published their landmark study about mechanisms of obstructive sleep apnea (OSA). Key observations were that the airway remained closed/narrowed even though tongue activity was increasing and that the airway opened with a disproportionate surge in tongue activity associated with arousal. This, along with concurrent increase in negative pharyngeal pressure, led them to propose the “balance of forces” theory; when the airway obstructs (i.e., narrows enough to impede normal flow demand), asphyxia develops and tongue activity increases, tending to pull the tongue forward, but, because of concurrent diaphragm activation, the negative pressure behind the tongue also increases, countering the forward tongue movement. This continues until there is arousal-mediated recruitment of the airway dilator muscles.

 

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Temple JL, Bernard C, Lipshultz SE, Czachor JD, Westphal JA and Mestre MA (2017) The Safety of Ingested Caffeine: A Comprehensive Review. Front. Psychiatry 8:80. doi: 10.3389/fpsyt.2017.00080

Caffeine is the most widely consumed psychoactive drug in the world. Natural sources of caffeine include coffee, tea, and chocolate. Synthetic caffeine is also added to products to promote arousal, alertness, energy, and elevated mood. Over the past decade, the introduction of new caffeine-containing food products, as well as changes in con-sumption patterns of the more traditional sources of caffeine, has increased scrutiny by health authorities and regulatory bodies about the overall consumption of caffeine and its potential cumulative effects on behavior and physiology. Of particular concernis therate of caffeine in take among populations potentially vulnerable to the negative effects of caffeine consumption: pregnant and lactating women, children and adolescents, young adults, and people with underlying heart or other health conditions, such as mental illness. Here, were view there search in to the safety and safe doses of ingested caffeine in healthy and in vulnerable populations. Were port that, for healthy adults, caffeine consumption is relatively safe, butthat for some vulnerable populations, caffeine con-sumption could be harmful, including impairments in cardiovascular function, sleep, and substance use. We also identified several gaps in the literature on which we based recommendations for the future of caffeine research.

 

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Vivien C Abad, Christian Guilleminault, New developments in the management of Narcolepsy, Nature and Science of Sleep 2017:9 39–57

Narcolepsyis a life-long, under recognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an auto immuneetiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities all eviate the main symptoms of excessive day time somnolence (EDS) and cataplexy and, to a lesserextent, reduce nocturnal sleep disruption, hypnagogich allucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyricacid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogich allucinations, and sleep paralysis. Various antidepressant medications including no repinephrine serotoninre up take inhibitors, selective serotonin reuptake inhibitors, and tricyclicanti depressants are second line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to preventhy pocretin neuronal death. Non hypocretin- based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinicaltrials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyricacid (GABA) modulationwith GABAA receptor agonists clarithromycin and flumazenil may help day time somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretinpeptide replacement administeredei ther through an intra cerebro ventricular routeor intra nasal route. Hypocretin neuronal transplant and transforming stemcells in to hypothalamic neurons are also discussed in this article. Immunotherapy to preventhy pocretin neuronal de a this reviewed.

 

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