A novel approach to the assessment of higher-order rule learning in male mice.

Historically, the development of valid and reliable methods for assessing higher-order cognitive abilities (e.g., rule learning and transfer) has been difficult in rodent models.

Rapid auditory processing and medial geniculate nucleus anomalies in Kiaa0319 knockout mice.

Developmental dyslexia is a common neurodevelopmental disorder characterized by difficulties in reading and writing. Although underlying biological and genetic mechanisms remain unclear, anomalies in phonological processing and auditory processing have been associated with dyslexia. Several candidate risk genes have also been identified, with KIAA0319 as a main candidate.

Peripheral Anomalies in USH2A Cause Central Auditory Anomalies in a Mouse Model of Usher Syndrome and CAPD.

Central auditory processing disorder (CAPD) is associated with difficulties hearing and processing acoustic information, as well as subsequent impacts on the development of higher-order cognitive processes (i.e., attention and language).

Communication-related assessments in an Angelman syndrome mouse model.

Introduction: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by motor deficits, seizures, some autistic-like behaviors, and severe impairment of speech. A dysfunction of the maternally imprinted UBE3A gene, coupled with a functional yet silenced paternal copy, results in AS. Although studies of transgenic mouse models have revealed a great deal about neural populations and rescue timeframes for specific features of AS, these studies have largely failed to examine intermediate phenotypes that contribute to the profound communicative disabilities associated with AS.

Effort-related decision making in humanized COMT mice: Effects of ValMet polymorphisms and possible implications for negative symptoms in humans.

Catechol-o-methyltransferase (COMT) is an enzyme that metabolizes catecholamines, and is crucial for clearance of dopamine (DA) in prefrontal cortex. ValMet polymorphism, which causes a valine (Val) to methionine (Met) substitution at codon 158, is reported to be associated with human psychopathologies in some studies. The Val/Val variant of the enzyme results in higher dopamine metabolism, which results in reduced dopamine transmission.

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development.

Shank3B mutant mice display pitch discrimination enhancements and learning deficits.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a core set of atypical behaviors in social-communicative and repetitive-motor domains. Individual profiles are widely heterogeneous and include language skills ranging from nonverbal to hyperlexic. The causal mechanisms underlying ASD remain poorly understood but appear to include a complex combination of polygenic and environmental risk factors.

Evaluation of visual motion perception ability in mice with knockout of the dyslexia candidate susceptibility gene Dcdc2.

Developmental dyslexia is a heritable disability characterized by difficulties in learning to read and write. The neurobiological and genetic mechanisms underlying dyslexia remain poorly understood; however, several dyslexia candidate risk genes have been identified. One of these candidate risk genes-doublecortin domain containing 2 (DCDC2)-has been shown to play a role in neuronal migration and cilia function.

Abuse potential of intravenous oxycodone/naloxone solution in nondependent recreational drug users.

Background And Objective: Abuse of opioid analgesics has become a public health issue. Some opioid abusers use intravenous administration to increase the magnitude of positive reinforcing effects. Intravenous co-administration of oxycodone with naloxone, an opioid antagonist, may reduce these rewarding effects and discourage abuse.

Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users.

The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg).

Attractiveness of reformulated OxyContin(R) tablets: assessing comparative preferences and tampering potential.

Reformulated OxyContin® (oxycodone HCl controlled-release or ORF) was developed as a tamper and abuse-deterrent product, to reduce the risk of product abuse, misuse and their consequences. This noninterventional single-session study asked participants who were medically-healthy recreational opioid users, aged 18 years and older, to consider how they would use commonly available supplies to tamper with placebo ORF and placebo original OxyContin (OC) tablets, and how they would assess the attractiveness of tampering and abusing ORF tablets, as compared with other opioid formulations. Participants provided information on past opioid use, and they assessed the properties of five nonhypothetical oxycodone products and two hypothetical oxycodone products.

Pharmacokinetics, tolerability, and safety of intranasal administration of reformulated OxyContin(®) tablets compared with original OxyContin (®) tablets in healthy adults.

Background And Objective: Reformulated OxyContin(®) (oxycodone-HCl controlled release) tablets (ORF) became available in the United States in August 2010. The original formulation of OxyContin(®) (oxycodone-HCl controlled release) tablets (OC) used a delivery system that did not provide inherent resistance to crushing and dissolving. The objective of this study was to compare the pharmacokinetics, tolerability, and safety of finely crushed ORF tablets, coarsely crushed ORF tablets, and finely crushed OC tablets.

Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following administration of a once-weekly buprenorphine transdermal system.

Background And Objective: Buprenorphine is extensively metabolized by cytochrome P450 (CYP) 3A4. This study evaluated the effect of ketoconazole, a CYP3A4 inhibitor, on the metabolism of buprenorphine following the administration of a buprenorphine transdermal system 10 μg/hour (BTDS 10).

Methods: This single-centre study enrolled 20 healthy subjects who had demonstrated ketoconazole-mediated CYP3A4 inhibition via an erythromycin breath test.

High-performance liquid chromatographic assay for two rifamycin-derived hypocholesterolemic agents in liver and biological fluids.

CGP 43371 (compound I), a mono-pivaloyl oxazole derivative of a 3-piperazino-rifamycin, has been in clinical trials as a potential hypocholesterolemic agent. A reversed-phase high-performance liquid chromatographic (HPLC) assay was developed using a C18 column and a gradient solvent system of methanol-0.1 M sodium acetate, pH 4.

Prinomide tromethamine pharmacokinetics: mutually dependent saturable and competitive protein binding between prinomide and its own metabolite.

Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and its metabolite were dose proportional. The nonlinear pharmacokinetic behavior of total prinomide and p-hydroxy metabolite was found to be caused by both saturable and mutually dependent competitive Langmuir-type plasma protein binding between prinomide and its p-hydroxy metabolite.

Acetylcholine formation from glucose following acute choline supplementation.

The effects of choline administration on acetylcholine metabolism in the central nervous system are controversial. Although choline supplementation may elevate acetylcholine (ACh) content in brain, turnover studies with labelled choline precursors suggest that systemic choline administration either has no effect or actually diminishes brain ACh synthesis. Since choline supplementation elevates brain choline levels, the apparent decreases in previous turnover studies may reflect dilution of the labelled choline precursor pool rather than altered ACh formation.

Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects.

Several epidemiological studies suggest an inverse relationship between fiber intake and colon cancer risk. Animal model studies indicate that this inhibitory effect depends on the source of dietary fiber. Because of the potential significance of certain colonic mutagens and secondary bile acids in the pathogenesis of colon cancer, the effect of types of supplemental fiber on fecal mutagens and bile acids was studied in human volunteers.

Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease.

A report of cell loss in the nucleus basalis of Meynert in patients with Wernicke-Korsakoff disease prompted the examination of thiamine pyrophosphate (TPP)-dependent enzymes in the brain and peripheral tissues of patients with Alzheimer's disease. In these brains, the activities of the 2-ketoglutarate dehydrogenase complex were reduced more than 75% and those of transketolase more than 45%. Decreases occurred in histologically damaged and in relatively undamaged areas.

In vivo brain calcium homeostasis during aging.

Since in vitro experiments suggest that brain calcium metabolism is altered with aging, the estimated rate of calcium uptake by the brain in vivo was determined with senescence. Calcium-45 incorporation into cortex, striatum, hippocampus, cerebellum, forebrain, midbrain and brainstem was determined in 3-, 10- and 30-month-old mice at 5 h after either an intravenous or intraperitoneal injection. Calcium uptake (brain dpm/mg protein divided by blood specific activity at 5 h) into these regions declined 19-33% at 10 months and 41-51% at 30 months.

Functional abnormalities of islets of Langerhans of obese hyperglycemic mouse.

Glucose-induced insulin release was studied in vitro with isolated islets of Langerhans obtained from obese hyperglycemic C57Bl/6J-ob/ob (ob/ob) and lean C57Bl/6J-+/+ (control) mice. The threshold concentrations of glucose for insulin release were determined. In addition, the effect of total fast and of chronic food restriction on in vitro insulin release were studied.

Reversal of somatostatin inhibition of insulin and glucagon secretion.

These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.

Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased "large glucagon-immunoreactivity".

Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon.

Elevated plasma proglucagon-like component with a glucagon-secreting tumor. Effect of streptozotocin.

To determine the character of the glucagon secretion and its modification by streptozotocin, were studied the plasma of a patient with recurrent pancreatic alpha-cell carcinoma. The plasma immunoreactive glucagon level before treatment of 4.80 ng per milliliter.

The effect of fasting on tissue cyclic cAMP and plasma glucagon in the obese hyperglycemic mouse.

The effect of 48 h of fasting in C57B1/6J-ob/ob and +/+ mice on body weight (BW), blood glucose (BG), serum immunreactive insulin (IRI), plasma immunoreactive glucagon (IRG) and on tissue levels of cyclic adenosine monophosphate (cAMP) were studied. Both groups of mice lost weight and demonstrated a decrease in BG and IRI with fasting. However, the BG and IRI of the ob/ob animals were initially highter and remained higher than those of the 2% of their initial weight while the +/+ lost 14 %.