Journal of internal medicine
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In line with increasing numbers of transgender (trans) and gender nonbinary people requesting hormone treatment, the body of available research is expanding. More clinical research groups are presenting data, and the numbers of participants in these studies are rising. Many previous review papers have focused on all available data, as these were scarce, but a more recent literature review is timely. ⋯ Existing epidemiological data suggest that the use of (certain) estrogens in trans women induces an increased risk of myocardial infarction and stroke, the reason that lifestyle management can be an integral part of trans health care. The observed cancer risk in trans people does not exceed the known cancer-risk differences between men and women. Now it is time to integrate the mostly reassuring data, to leave the overly cautious approach behind, to not copy the same research questions repeatedly, and to focus on longer follow-up data with larger cohorts.
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The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are widely distributed across the brain and involved in a myriad of neurophysiological functions that include sleep, arousal, feeding, reward, fear, anxiety and cognition. Hcrt cell loss in humans leads to narcolepsy with cataplexy (narcolepsy type 1), a disorder characterized by intrusions of sleep into wakefulness, demonstrating that the Hcrt system is nonredundant and essential for sleep/wake stability. ⋯ Circuit neuroscience findings suggest that the Hcrt system is a hub that integrates diverse inputs modulating arousal (e.g., circadian rhythms, metabolic status, positive and negative emotions) and conveys this information to multiple output regions. This neuronal architecture explains the wealth of physiological functions associated with Hcrts and highlights the potential of the Hcrt system as a therapeutic target for a number of disorders. We discuss present and future possible applications of drugs targeting the Hcrt system for the treatment of circuit-related neuropsychiatric and neurodegenerative conditions.
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Review
RNAi therapy with givosiran significantly reduces attack rates in acute intermittent porphyria.
Acute hepatic porphyria (AHP) is a group of inherited metabolic disorders that affect hepatic heme biosynthesis. They are associated with attacks of neurovisceral manifestations that can be life threatening and constitute what is considered an acute porphyria attack. Until recently, the sole specific treatment for acute porphyria attacks consisted of the intravenous administration of hemin. ⋯ The results of clinical trials have shown that givosiran treatment leads to a rapid and sustained reduction of ALAS1 mRNA, decreased heme precursor levels, and a decreased rate of acute attacks compared with placebo. The clinical trials (phases I, II, and III) were all randomized and placebo controlled. Many patients enrolled in the initial clinical trials have continued treatment in open label extension and extended/compassionate-use programs in countries where givosiran is not yet commercially available.
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Glucagon-like peptide-1 (GLP-1) is a peptide derived from differential processing of the precursor for the hormone glucagon. It is secreted predominantly by endocrine cells in the gut epithelium in response to nutrient stimulation. Studies from the last 35 years have given us an idea about its physiological functions. ⋯ In this review, I first discuss whether the processing of proglucagon may also result in GLP-1 formation in the pancreas and in glucagon in the gut. Next, I discuss the relationship between the physiological actions of GLP-1 and the therapeutic effects of the GLP-1 receptor agonists, which are far from being congruent and generally poorly understood. These relationships illustrate both the difficulties and the benefits of bridging results obtained in the laboratory with those emerging from the clinic.