Complementary and alternative medicine use in narcolepsy.

BACKGROUND: Management of narcolepsy includes behavior strategies and symptomatic pharmacological treatment. In the general population, complementary and alternative medicine (CAM) use is common in Europe (30%), also in chronic neurological disorders (10-20%). The aim of our study was to evaluate frequency and characteristics of CAM use in German narcolepsy patients. METHODS: Demographic, disease-related data frequency and impact of CAM use were assessed in an online survey. Commonly used CAM treatments were predetermined in a questionnaire based on the National Center for Complementary and Alternative Medicine and included the domains: (1) alternative medical systems; (2) biologically based therapies; (3) energy therapies; (4) mind-body interventions, and (5) manipulative and body-based therapies. RESULTS: We analyzed data from 254 questionnaires. Fifteen percent of participants were at the time of survey administration using CAM for narcolepsy, and an additional 18% of participants reported past use. Among the 33% of CAM users, vitamins/trace elements (54%), homoeopathy (48%) and meditation (39%) were used most frequently. 54% of the users described CAM as helpful. CAM users more frequently described having side effects from their previous medication (p = 0.001), and stated more frequently not to comply with pharmacological treatment than non-CAM users (21% vs. 8%; p = 0.024). DISCUSSION: The use of CAM in narcolepsy patients is common. Our results indicate that many patients still feel the need to improve their symptoms, sleepiness and psychological well-being in particular. Frequent medication change, the experience of adverse events and low adherence to physician-recommended medication appears more frequent in CAM users. The impact of CAM however seems to be limited.

Real-world treatment of pediatric narcolepsy with pitolisant: A retrospective, multicenter study.

BACKGROUND: First symptoms of narcolepsy mostly present during childhood. Pharmacological management options in children are limited, also due to approval status. Pitolisant is an inverse histamine 3 receptor agonist and has been approved for the treatment of adult narcolepsy with or without cataplexy by EMA and FDA. Clinical experience indicates for a beneficial use also in children and adolescents. Our goal was to evaluate the effects and tolerability of pitolisant in narcolepsy children/adolescents in a real-world setting. METHODS: This multicentre retrospective observational study included 55 patients with narcolepsy from three international narcolepsy centers (Germany, France and Italy) who were treated with pitolisant. Patients were eligible if they were at least 6 years old and diagnosed with narcolepsy type 1 or 2. Demographic and clinical characteristics, questionnaires, sleep medicine and laboratory data were collected. RESULTS: 55 children/adolescents (25 girls, 45.45%, 30 boys, 54.55%) aged 6-18 years, with narcolepsy (type 1 = 92.7%, type 2 = 7.3%), were treated with pitolisant. The mean pitolisant dose was 34.1 mg/d. Treatment was effective for excessive daytime sleepiness (EDS) and cataplexy: the pediatric Epworth Sleepiness Scale (ESS) score decreased from 19 to 13.5 (p < 0.001) and the weekly cataplexy frequency improved from 7.9 at baseline to 5.2 (p < 0.001). Treatment with pitolisant was well tolerated. Side effects were mild and mostly short-term. Insomnia was reported most frequently (5.5%). CONCLUSION: First real-world results suggest that pitolisant treatment is effective in improving EDS and cataplexy in children with narcolepsy, and also is well tolerated.

[Narcolepsy in adults: Definition, etiology and treatment]. / Narkolepsie im Erwachsenenalter: Definition, Ätiologie und Behandlung.

Narcolepsy is a hypersomnolence disorder of central origin that presents with a disturbance of the wake-sleep regulation. Lead symptoms consist of excessive daytime sleepiness and cataplexy. Nowadays, two types of narcolepsy are distinguished. Type 1 narcolepsy, formerly known as narcolepsy with cataplexy, is based on hypocretin deficiency. The cause of type 2 narcolepsy, formerly known as narcolepsy without cataplexy, remains mainly unknown. A multimodal approach is necessary for diagnosis. The mean latency between the onset of disease and diagnosis in Europe ranges 14 years. Narcolepsy has a major impact on workability and quality of life. The management of narcolepsy is usually life-long and includes non-pharmacological approaches and a symptomatic pharmacological treatment.

Sperm-Activating Odorous Substances in Human Follicular Fluid and Vaginal Secretion: Identification by Gas Chromatography-Olfactometry and Ca2+ Imaging.

Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography-olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor-ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α-androst-16-en-3-one and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, are shown.

Chemosensory Ca2+ dynamics correlate with diverse behavioral phenotypes in human sperm.

In the female reproductive tract, mammalian sperm undergo a regulated sequence of prefusion changes that "prime" sperm for fertilization. Among the least understood of these complex processes are the molecular mechanisms that underlie sperm guidance by environmental chemical cues. A "hard-wired" Ca(2+) signaling strategy that orchestrates specific motility patterns according to given functional requirements is an emerging concept for regulation of sperm swimming behavior. The molecular players involved, the spatiotemporal characteristics of such motility-associated Ca(2+) dynamics, and the relation between a distinct Ca(2+) signaling pattern and a behavioral sperm phenotype, however, remain largely unclear. Here, we report the functional characterization of two human sperm chemoreceptors. Using complementary molecular, physiological, and behavioral approaches, we comparatively describe sperm Ca(2+) responses to specific agonists of these novel receptors and bourgeonal, a known sperm chemoattractant. We further show that individual receptor activation induces specific Ca(2+) signaling patterns with unique spatiotemporal dynamics. These distinct Ca(2+) dynamics are correlated to a set of stimulus-specific stereotyped behavioral responses that could play vital roles during various stages of prefusion sperm-egg chemical communication.

Cell-selective, apoptosis-inducing rhodium(III) crown thiaether complexes.

Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF-7 and HT-29 and immortalized HEK-293 cells indicate that the dicationic kappa(2)N(imino) complexes [([9]aneS(3))RhCl(pp)](2+) are much more active than monocationic complexes [([9]aneS(3))RhCl(2)(L)](+) (L=imidazole, CH(3)CN). Whereas the kappa(2)N(amino) complex [([9]aneS(3))RhCl(piperazine)](2+) is inactive, replacing piperazine with the structurally analogous kappa(2)S (thiaether) ligand 1,4-dithiane restores cytotoxicity as evidenced by IC(50) values in the range 8.1-11.6 microM. Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC(50) values: 4.7-8.9 microM) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC(50) values: 0.6-1.9 microM) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7. A comparative annexin V-propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.

Odorant-receptor interactions and odor percept: a chemical perspective.

Receptor-ligand interaction models are generally based on a 'lock and key' concept. How far this holds true for olfactory receptors and odor molecules is currently uncertain. Here, we have investigated the response of a human olfactory receptor, OR1D2, to a broad array of odorants and found that there is no simple, direct correlation between a molecule's ability to activate this receptor and the odor impression elicited in the brain. In a parallel study on specific anosmia, we have found no evidence for odor-specific anosmia to either musk or amber, but rather to specific molecules within these categories. Cluster analysis confirmed that there is no simple correlation between molecular structure and impaired perception in either odor type. There are some differences in patterns of impairment between the two odor types and some evidence to suggest that subjects with specific anosmia to a given substance can identify its presence in a mixture. Taken together, our results show that simplistic 'lock and key' models of olfaction based on a concept of odor-quality-tuned receptors are inadequate, irrespective of the nature of the lock-key interaction. Receptor activation is only one step in a long chain of events leading from inhalation of odorants to perception of odor in the higher brain, and, therefore, although structure-odor correlations are useful tools for the design of novel odorants, caution should be exercised when extrapolating them to models of olfactory perception. Those seeking to understand the odorant-receptor interaction should use receptor activation rather than odor as input data.