A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder.

Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting an estimated 283 million individuals worldwide, with substantial health and economic consequences. Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, have shown promise in preclinical studies as potential therapeutic targets for AUD. In this human laboratory study, we aimed to translate preclinical findings on the PPAR-α agonist fenofibrate to a human population with current AUD.

Preclinical and clinical evidence for suppression of alcohol intake by apremilast.

Treatment options for alcohol use disorders (AUDs) have minimally advanced since 2004, while the annual deaths and economic toll have increased alarmingly. Phosphodiesterase type 4 (PDE4) is associated with alcohol and nicotine dependence. PDE4 inhibitors were identified as a potential AUD treatment using a bioinformatics approach.

Gabapentin for the treatment of alcohol use disorder.

Alcohol misuse is the fifth leading risk factor for premature death and disability worldwide. Fewer than 10% of afflicted Americans receive pharmacological treatment for alcohol use disorder. Gabapentin is a calcium channel GABAergic modulator that is widely used for pain.

Genetic variants associated with sleep disorders.

Objective: The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable; therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our understanding of the polymorphisms associated with the phenotypes of particular sleep disorders.

Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep cycles.

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography.

Gabapentin treatment for alcohol dependence: a randomized clinical trial.

Importance: Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.

Objective: To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.

Design, Participants And Setting: A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.

A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence.

Wrist actigraphic scoring for sleep laboratory patients: algorithm development.

Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep-wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory.

Genotyping sleep disorders patients.

Objective: The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting.

Methods: To assess the validity of several candidate associations, we obtained saliva deoxyribonucleic acid (DNA) samples and clinical information from 360 consenting research participants who were undergoing clinical polysomnograms.

CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic control during sleep.

Background: Type 2 diabetes and obstructive sleep apnea (OSA) are frequently comorbid conditions. OSA is associated with increased insulin resistance, but studies of continuous positive airway pressure (CPAP) have shown inconsistent effects on glycemic control. However, endpoints such as hemoglobin A1c and insulin sensitivity might not reflect short-term changes in glycemic control during sleep.

Evaluation of immobility time for sleep latency in actigraphy.

Background: Actigraphy has become an important tool in sleep research, however, most actigraphic models have had little evaluation of their sleep scoring software. Some reports have described poor agreement of actigraph and polysomnogram (PSG) results. In this study, we examined the accuracy of the Actiwatch-L instrument with Actiware((R)) software version 5.

Nasal cytology: a marker of clinically silent inflammation in patients with obstructive sleep apnea and a predictor of noncompliance with nasal CPAP therapy.

Study Objectives: Patients with obstructive sleep apnea treated with nasal continuous positive airway pressure (CPAP) often complain of nasal side effects. We studied patients before and after initiation of nasal CPAP to see how treatment affected nasal function and markers of nasal inflammation. We searched for pretreatment findings that might help to predict noncompliance.

Circadian tempo: a paradigm for genome stability?

Circadian clocks are molecular time-keeping systems that underlie daily biological rhythms in anticipation of the changing light and dark cycles. These clocks mediate daily rhythms in physiology and behavior that are thought to confer an adaptive advantage for organisms. It is hypothesized that cell cycle checkpoints are gated to an intrinsic circadian clock to protect DNA from diurnal exposure to mutagens (e.

A circadian model for viral persistence.

Persistently infecting DNA viruses depend heavily on host cell DNA synthesis machinery. Replication of cellular and viral DNA is inhibited by mutagenic stress. It is hypothesized that diurnal regulation of viral DNA replication may occur at the level of cell cycle checkpoints and DNA repair, to protect DNA from exposure to UV light or other mutagens.

Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262.

Background: In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH). Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes.

Zolpidem for postanoxic spasticity.

A 28-year-old male sustained anoxic brain damage following aborted cardiac arrest, and subsequently developed severe muscular rigidity and spasticity involving all extremities. The spasticity was refractory to the standard regimens used for spastic hypertonia. Zolpidem dramatically inhibited muscular rigidity, spasticity, and dystonic posturing in a dose-dependent manner, resulting in a sustained improvement of his global performance over four years.