Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity.

Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function.

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig.

Dynorphin release by the lateral olivocochlear efferents may inhibit auditory nerve activity: a cochlear drug delivery study.

Dynorphin (dyn) is suggested to excite the auditory nerve (AN) when released by the lateral olivocochlear (LOC) efferents. However, previous studies evaluated either intravenously delivered dyn-like agents, raising the potential for systemic (central) effects, or agent concentrations unlikely to be achieved via endogenous cochlear release. This study tested the hypothesis that biologically relevant increases in dyn levels in the cochlea achieved via diffusion of the drug of (-)pentazocine across the round window membrane enhances AN firing.

Age-related GABAA receptor changes in rat auditory cortex.

Auditory cortex (AI) shows age-related decreases in pre-synaptic markers for gamma-aminobutyric acid (GABA) and degraded AI neuronal response properties. Previous studies find age-related increases in spontaneous and driven activity, decreased spectral and directional sensitivity, and impaired novelty detection. The present study examined expression of GABA(A) receptor (GABA(A)R) subunit message, protein, and quantitative GABA(A)R binding in young, middle-aged, and aged rat AI, with comparisons with adjoining parietal cortex.

Acoustic experience alters the aged auditory system.

Objectives: Presbyacusis, one of the most common ailments of the elderly, is often treated with hearing aids, which serve to reintroduce some or all of those sounds lost to peripheral hearing loss. However, little is known about the underlying changes to the ear and brain as a result of such experience with sound late in life. The present study attempts to model this process by rearing aged CBA mice in an augmented acoustic environment (AAE).

l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice.

l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties.

Time course of tinnitus development following noise exposure in mice.

Gap-induced prepulse inhibition of acoustic startle (GPIAS) has been used in rats and mice to study the problem of tinnitus. The current study demonstrates that similar methods can be used to study the temporal development of tinnitus over time in middle-aged mice. Six-month-old mice on a mixed C57Bl6 × 129 background were anesthetized with isoflurane and exposed to unilateral noise (n = 15), or sham exposure for controls (n = 8), for 1 hr (16-kHz octave band signal, 116-dB SPL).

MDAN-21: A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys.

MDAN-21, 7'-{2-[(7-{2-[({(5α, 6α)-4,5-Epoxy-3,14-dihydroxy-17-methylmorphin-6-yl}-aminocarbonyl)metoxy]-acetylamino}-heptylaminocarbonyl)-methoxy]-acetylamino}-naltrindole, a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice. Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors.

Metabolic effects of intra-abdominal fat in GHRKO mice.

Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are growth hormone (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate the unexpected coexistence of adiposity with improved insulin sensitivity and extended longevity, we examined effects of surgical removal of visceral (epididymal and perinephric) fat on metabolic traits related to insulin signaling and longevity. Comparison of results obtained in GHRKO mice and in normal animals from the same strain revealed disparate effects of visceral fat removal (VFR) on insulin and glucose tolerance, adiponectin levels, accumulation of ectopic fat, phosphorylation of insulin signaling intermediates, body temperature, and respiratory quotient (RQ).

D-methionine (D-met) significantly rescues noise-induced hearing loss: timing studies.

We have previously reported rescue from noise-induced auditory brainstem response (ABR) threshold shifts with d-methionine (d-met) administration 1 h after noise exposure. The present study investigated further d-met rescue intervals at 3, 5 and 7 h post-noise exposure. Chinchillas laniger were exposed to a 6 h 105 dB sound pressure level (dB SPL) octave band noise (OBN) and then administered d-met i.

Development of the Edmonson Psychiatric Fall Risk Assessment Tool.

The purpose of this study was to develop a fall risk assessment instrument for the inpatient psychiatric population. Nine risk factors were identified through a review of the literature. The instrument was applied retrospectively to patient records, and the percentage of those who fell who triggered each of the items in each domain was calculated.

Incidence, prevalence, and under-recognition of delirium in urology patients.

Unrecognized delirium may lead to negative outcomes, such as increased morbidity, longer hospital stays, and increased health care costs. A prospective cohort design study was used to determine the incidence and prevalence of delirium and percentage of patients with unrecognized delirium in a hospital inpatient unit. The sample consisted of 141 patients admitted to a urology/nephrology unit over a six-week period.

Connecting serum IGF-1, body size, and age in the domestic dog.

Many investigations in recent years have targeted understanding the genetic and biochemical basis of aging. Collectively, genetic factors and biological mechanisms appear to influence longevity in general and specifically; reduction of the insulin/IGF-1 signaling cascade has extended life span in diverse species. Genetic alteration of mammals for life extension indicates correlation to serum IGF-1 levels in mice, and IGF-1 levels have been demonstrated as a physiological predictor of frailty with aging in man.

Lack of association of a spontaneous mutation of the Chrm2 gene with behavioral and physiologic phenotypic differences in inbred mice.

The nucleotide substitution C797T in the Chrm2 gene causes substitution of leucine for proline at position 266 (P266L) of the CHRM2 protein. Because Chrm2 codes for the type 2 muscarinic receptor, this mutation could influence physiologic and behavioral phenotypes of mice. Chrm2 mRNA was not differentially expressed in 2 brain regions with high cholinergic innervation in a mouse strain that does (BALB/cByJ) or does not (C57BL/6J) have the mutation.

Sleep, activity, temperature and arousal responses of mice deficient for muscarinic receptor M2 or M4.

Aims: The type 2 muscarinic receptor (M2R) differs from the other G-protein-coupled muscarinic receptor (type 4, or M4R) in tissue distribution and physiologic effects. We studied the impact of these receptors on sleep and arousal by using M2R and M4R knock-out (KO) mice.

Main Methods: M2R and M4R KO and genetically intact mice were compared in terms of normal patterns of sleep, responses to sleep loss, infectious challenge and acoustic startle, and acoustic prepulse inhibition of startle (PPI).

Early prediction of response to chemoradiotherapy for head and neck cancer: reliability of restaging with combined positron emission tomography and computed tomography.

Objective: To assess the role of combined positron emission tomography and computed tomography (PET-CT) in predicting early treatment response at the primary site and in the neck after chemoradiotherapy (CRT) for advanced squamous cell carcinoma of the head and neck (SCCHN).

Design: Retrospective analysis with a median follow-up of 24 months.

Setting: Academic, tertiary referral center.

Processing of broadband stimuli across A1 layers in young and aged rats.

Presbycusis can be considered a slow age-related peripheral and central deterioration of auditory function which manifests itself as deficits in speech comprehension, especially in noisy environments. The present study examined neural correlates of a simple broadband noise stimulus in primary auditory cortex (A1) of young and aged Fischer-Brown Norway (FBN) rats. Age-related changes in unit responses to broadband noise bursts and spontaneous activity were simultaneously recorded across A1 layers using a single shank, 16-channel electrode.

Adenosine receptor antagonists and behavioral activation in NF-kappaB p50 subunit knockout mice.

Aims: Our previous work revealed that mice lacking the p50 subunit of transcription factor nuclear factor kappa B (NF-kappaB) (p50 KO mice) and genetically intact F2 mice have similar locomotion under basal conditions, yet p50 KO mice show greater locomotor activation after caffeine ingestion. In this report, we test whether KO mice display altered caffeine pharmacokinetics or increased caffeine-induced DA turnover relative to F2 mice, and evaluate the impact of intraperitoneal administration of specific adenosine and DA receptor antagonists on locomotor activity.

Main Methods: Concentrations of DA and caffeine were measured using high performance liquid chromatography.

Cochlear damage changes the distribution of vesicular glutamate transporters associated with auditory and nonauditory inputs to the cochlear nucleus.

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening.

Insulin sensitivity as a key mediator of growth hormone actions on longevity.

Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Prop1(df) and growth hormone receptor knockout [GHRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span.

Quantitative assessment of laryngeal muscle morphology after recurrent laryngeal nerve injury: right vs. left differences.

Objectives/hypothesis: Reports of laryngeal response to denervation are inconsistent. Some document atrophy and fibrosis in denervated laryngeal muscles, whereas others indicate resistance to atrophy. Spontaneous reinnervation has also been documented.

Risks of allergy vial contamination: comparison of mixing in-office versus under ventilation hood.

Objective: Compare the risk of bacterial contamination of allergy immunotherapy vials prepared in-office versus those mixed under a ventilation hood.

Study Design: Prospective single-blinded study.

Setting: Tertiary otolaryngology outpatient clinic.

The safety of multi-dose vials in allergy immunotherapy.

Objective: To prospectively evaluate the risks of vial contamination after routine clinical use of multiple-dose vials for immunotherapy.

Study Design: Prospective observational study of immunotherapy vial cultures from June 2007 to January 2008.

Setting: Tertiary care outpatient otolaryngology clinic.

Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system.

Aging and acoustic trauma may result in partial peripheral deafferentation in the central auditory pathway of the mammalian brain. In accord with homeostatic plasticity, loss of sensory input results in a change in pre- and postsynaptic GABAergic and glycinergic inhibitory neurotransmission. As seen in development, age-related changes may be activity dependent.

Study of tracheal dyskinesia impact on the cardiac hemodynamics.

Background: Tracheal dyskinesia (TD) was recently recognized as a possible mechanism for acute pulmonary edema (Elamin and Firdose, J Bronchol 2004;11:118-21; Khan and Elamin Eur Respir J 2005;26:319). This study was designed to evaluate possible impact of TD on cardiac hemodynamics.

Methods: Patients were prospectively assigned to either study "A" or control "B" groups (TD >50% or <50%, respectively) diagnosed by bronchoscopy or dynamic chest computed tomography.