Comparative anisometropic study between the Turville infinity balance test and the monocular negative relative accommodation test

Comparative anisometropic study between the Turville infinity balance test and the monocular negative relative accommodation tes

A post hoc pooled analysis of exacerbations among US participants in randomized controlled trials of tiotropium

SummaryBackgroundExacerbations are a defining outcome of chronic obstructive pulmonary disease (COPD). We evaluated the effect of tiotropium on COPD exacerbations and related hospitalizations among patients from the USA enrolled in clinical trials.MethodsData were pooled from six randomized, double-blind, placebo-controlled trials (6 to ≥12 months' duration) of tiotropium in patients with COPD. Exacerbations were defined retrospectively as an increase in or new onset of >1 respiratory symptom lasting for ≥3 days and requiring treatment with systemic corticosteroids and/or antibiotics. Time to first exacerbation or hospitalization and exacerbation rates were analyzed at 6 months, and at 1 year for studies ≥1 year.ResultsIn total, 4355 patients (tiotropium, 2268, placebo, 2087; mean age 66.5 years; forced expiratory volume in 1 s [FEV1] 1.03 L [35.5% predicted]) were analyzed at 6 months and 2455 at 1 year (tiotropium 1317, placebo 1138; mean age 65.5 years; FEV1 1.03 L [37.0% predicted]). Tiotropium delayed time to first exacerbation or first hospitalized exacerbation at 6 months (hazard ratios [HRs], 0.80, 0.65, respectively; p < 0.001 vs placebo) and 1 year (HRs, 0.73 and 0.55; p < 0.001 vs placebo) and reduced exacerbation rates and hospitalization rates (6 months: HRs, 0.79, 0.64; 1 year: HRs, 0.78, 0.56, respectively; all p < 0.01 vs placebo). Tiotropium significantly reduced exacerbations, irrespective of inhaled corticosteroid use at baseline. Tiotropium was not associated with an increased risk of cardiac-related events.ConclusionsTiotropium significantly reduced the risk and rates of exacerbations and hospitalizations among US patients with COPD

Elevated anxiety-like behavior following ethanol exposure in mutant mice lacking neuropeptide Y (NPY)

Neuropeptide Y (NPY) is a neuromodulator with anxiolytic properties. Recent evidence suggests that NPY modulates neurobiological responses to ethanol. Because withdrawal from ethanol is associated with elevated anxiety-like behavior, and because central NPY modulates anxiety, we assessed anxiety-like behavior in mutant mice lacking normal production of NPY (NPY−/−) and in normal wild-type mice (NPY+/+) 6-hours after removal of a liquid diet containing 4.5% ethanol

Predictors of High Ethanol Consumption in RII?? Knock-Out Mice: Assessment of Anxiety and Ethanol-Induced Sedation

Genetic and pharmacological evidence suggests that the cyclic adenosine monophosphate–dependent protein kinase A pathway modulates neurobiological responses to ethanol. Mutant mice lacking the RIIβ subunit of protein kinase A (RIIβ) are resistant to ethanol-induced sedation and drink significantly more ethanol than littermate wild-type mice (RIIβ). We determined whether high ethanol intake by the RIIβ mice on alternate genetic backgrounds is reliably predicted by high basal levels of anxiety or resistance to the sedative effects of ethanol. Two-bottle choice procedures and a battery of behavioral tests (elevated plus maze, open-field activity, and zero maze) were used to assess voluntary ethanol consumption and basal levels of anxiety in RIIβ and RIIβ mice on either a C57BL/6J or a 129/SvEv × C57BL/6J genetic background. Additionally, ethanol-induced sedation and blood ethanol levels were determined in RIIβ and RIIβ mice after intraperitoneal injection of ethanol (3.8 g/kg). RIIβ mice on both genetic backgrounds consumed more ethanol and had a greater preference for ethanol relative to RIIβ mice. However, RIIβ mice showed reduced basal levels of anxiety when maintained on the C57BL/6J background but showed increased anxiety when maintained on the 129/SvEv × C57BL/6J background. Consistent with prior research, RIIβ mice were resistant to the sedative effects of ethanol, regardless of the genetic background. Finally, RIIβ and RIIβ mice showed similar blood ethanol levels. These results indicate that high ethanol consumption is associated with resistance to the sedative effects of ethanol but that basal levels of anxiety, as well as ethanol metabolism, do not reliably predict high ethanol drinking by RIIβ mice

The Alcohol Deprivation Effect (ADE) in C57BL/6J mice is observed using operant self-administration procedures and is modulated by CRF-1 receptor signaling

The alcohol deprivation effect (ADE) is characterized by transient excessive alcohol consumption upon reinstatement of ethanol following a period of ethanol deprivation. While this phenomenon has been observed in rats using both bottle drinking (consummatory behavior) and operant self-administration (consummatory and appetitive “ethanol-seeking” behavior) procedures, ADE studies in mice have primarily relied on bottle drinking measures. Furthermore, the neurochemical pathways that modulate the ADE are not well understood. Therefore, we determined whether the ADE can be observed in C57BL/6J mice using operant self-administration procedures and if expression of the ADE is modulated by the corticotropin releasing factor-1 (CRF-1) receptor

Blockade of the Corticotropin Releasing Factor Type 1 Receptor Attenuates Elevated Ethanol Drinking Associated With Drinking in the Dark Procedures

Drinking in the dark (DID) procedures have recently been developed to induce high levels of ethanol drinking in C57BL/6J mice, which result in blood ethanol concentrations (BECs) reaching levels that have measurable affects on physiology and/or behavior. The present experiments determined whether the increased ethanol drinking caused by DID procedures can be attenuated by pretreatment with CP-154,526; a corticotropin releasing factor type-1 (CRF1) receptor antagonist

Peripheral and Central Administration of a Selective Neuropeptide Y Y1 Receptor Antagonist Suppresses Ethanol Intake by C57BL/6J Mice

Neuropeptide Y (NPY) is a 36–amino acid neuromodulator that is expressed throughout the central nervous system. Recent genetic and pharmacological evidence suggests that the NPY Y1 receptor modulates ethanol intake. To further characterize the role of the Y1 receptor, we examined voluntary ethanol consumption by mice after administration of [(−)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-tiazol-2-yl)ethyl]-4-morpholinopyridine] (compound A), a novel and selective Y1 receptor antagonist (Y1RA) that acts centrally on brain receptors when administered peripherally