Sublingual zolpidem is more effective than oral zolpidem in initiating early onset of sleep in the post-nap model of transient insomnia: a polysomnographic study

ObjectiveOX22 is zolpidem formulated for sublingual administration. The primary objective of the present study was to evaluate the efficacy of single doses of sublingual zolpidem (5 and 10 mg) versus oral zolpidem (10 mg), with regard to latency to persistent sleep (LPS), in a post-nap model of insomnia.MethodsTwenty-one healthy volunteers included in this study were recorded by polysomnography during 2 consecutive nights and, on the day in between, during a 2 h nap. Eighteen out of these 21 subjects were finally analyzed. Treatment was randomly administered before the second recording night to subjects demonstrating at least 30 min of sleep during the nap recording.ResultsContrast analyses show that 10 mg OX22 significantly shortened LPS compared to oral zolpidem administration of 10 mg (12.8 ± 9.9 and 18.4 ± 11.3 min, respectively; p < .05). No treatment effects could be evidenced on total sleep time, time awake after sleep onset and sleep architecture parameters for OX22 compared to oral zolpidem. All treatments were well tolerated and did not induce next-day residual effects.ConclusionThe present results show that OX22, a sublingual formulation of zolpidem, has a significant earlier sleep initiation as compared to an equivalent dose of oral zolpidem in healthy volunteers in a post-nap model of insomnia.     

Bestrophin 2: An anion channel associated with neurogenesis in chemosensory systems

The chemosensory neuroepithelia of the vertebrate olfactory system share a life‐long ability to regenerate. Novel neurons proliferate from basal stem cells that continuously replace old or damaged sensory neurons. The sensory neurons of the mouse and rat olfactory system specifically express bestrophin 2, a member of the bestrophin family of calcium‐activated chloride channels. This channel was recently proposed to operate as a transduction channel in olfactory sensory cilia. We raised a polyclonal antibody against bestrophin 2 and characterized the expression pattern of this protein in the mouse main olfactory epithelium, septal organ of Masera, and vomeronasal organ. Comparison with the maturation markers growth‐associated protein 43 and olfactory marker protein revealed that bestrophin 2 was expressed in developing sensory neurons of all chemosensory neuroepithelia, but was restricted to proximal cilia in mature sensory neurons. Our results suggest that bestrophin 2 plays a critical role during differentiation and growth of axons and cilia. In mature olfactory receptor neurons, it appears to support growth and function of sensory cilia. J. Comp. Neurol. 515:585–599, 2009. © 2009 Wiley‐Liss, Inc.     

Receptor screening technologies in the evaluation of Amazonian ethnomedicines with potential applications to cognitive deficits

Ethnopharmacological relevance

Amazonian peoples utilize a variety of psychoactive plants that may contain novel biologically active compounds. Efforts to investigate such remedies in terms of neuropharmacology have been limited.

Aim of this study

This study identified Amazonian ethnomedicines with potential for the treatment of cognitive deficits in schizophrenia and dementias, and characterized their interactions with CNS neurotransmitter receptors in vitro.

Materials and methods

Approximately 300 Amazonian species with folk uses or constituents indicative of central nervous system activity were incorporated into a database constructed from literature searches, herbarium surveys, and interviews with traditional practitioners. Approximately 130 of these targeted species were collected in Loreto province, Peru, and 228 fractions derived from them were screened in 31 radioreceptor assays via the resources of the NIMH Psychoactive Drug Screening Program. A subset was also screened in functional assays at selected serotonin, muscarinic, and adrenergic receptors.

Results

Ninety-one samples displayed ≥60% inhibition of radioligand binding activity in receptor assays; 135 samples displayed agonist or antagonist activity (or both) in functional assays.

Conclusions

Potential CNS activity was detected in about 40% of the samples screened, with some correlations to both folk uses and phytochemical constituents. These results may point to novel and potentially therapeutic CNS active compounds.     

Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression

Background  

As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases.     

Change in diet and oral hygiene over an 8-week period: effects on oral health and oral biofilm

The aim of the study was to monitor changes in oral health and oral biofilm composition in vivo during an experiment simulating prehistoric lifestyle and diet and poor oral hygiene. Thirteen subjects lived for a period of 8 weeks under Neolithic conditions. The following clinical parameters were recorded before and after the project: gingival and plaque index (Löe and Silness, Acta Odontol Scand 21:533, 1963; Silness and Löe, Acta Odontol Scand 22:121–135, 1964), probing pocket depth, and bleeding upon probing. In addition, supragingival plaque samples were collected both before and after the project and were analysed quantitatively using multiplex fluorescence in situ hybridization and confocal laser scanning microscopy. The following plaque bacteria were evaluated: Streptococcus spp., Veillonella spp., Fusobacterium nucleatum, and Actinomyces naeslundii. The plaque index increased significantly from 1.12 up to 1.55 over the 8-week period (gingival index before, 0.46; after, 0.93; p < 0.05). A strong correlation of both indices was recorded before (r = 0.77) and after (r = 0.83) participation in the study. Each of the children in the study showed a progression of carious lesions and/or new areas of demineralisation. The probing pocket depth and bleeding upon probing were not affected. All subjects yielded an intra-individual shift in biofilm composition. The proportion of F. nucleatum decreased across all subjects. The proportion of Veillonella spp. increased among the children. Poor oral hygiene and change of diet lead to an increase in oral plaque and gingival inflammation. The inter-individual comparison indicated a shift in bacterial composition.     

Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats

In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness to homeostatic signals. Here we characterized the response of obese OVX rats to peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal replacement (17β-estradiol, 2 μg per 4 d; OVX+E) and were infused with vehicle or amylin (50 μg/kg · d) for 28 d. Amylin reduced body weight (5.1 ± 1.1%) and food intake (10.9 ± 3.4%) in SHAM rats but was twice as efficacious in OVX rats in reducing weight (11.2 ± 1.9%) and food intake (23.0 ± 2.0%). There were no differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic rate (～24%) and increased respiratory exchange ratio relative to SHAM. Amylin partially normalized metabolic rate (13% increase) in OVX rats and decreased respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis and increased immobility in the forced swim test. Additionally, amylin increased neurogenesis (～2-fold) within the area postrema of OVX rats. To assess the contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, amylin infusion reduced food intake but not body weight, whereas in OVX Zucker diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, amylin induced greater body weight loss in the absence of estradiol via central and peripheral actions that did not require leptin. These findings support the clinical investigation of amylin in low estradiol (e.g. postmenopausal) states.