Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain.

Background: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations.

Trace amine-associated receptor 1 activation silences GSK3β signaling of TAAR1 and D2R heteromers.

Trace amine-associated receptor 1 (TAAR1) activation by selective endogenous agonists modulates dopaminergic neurotransmission. This results in antipsychotic-like behavior in vivo which might be initiated by an interaction of TAAR1 and dopamine D2L receptor (D2R). Here we analyzed the functional link between TAAR1 and D2R using highly potent and selective TAAR1 agonists, and newly generated tools such as TAAR1 knock-out and TAAR1 overexpressing rats as well as specific anti-rat TAAR1 antibodies.

Influence of oxidative stress biomarkers on cognitive decline.

Background: Abnormal oxidative stress is an established feature of Alzheimer's disease (AD). Markers of lipoperoxidation and deficits in serum antioxidants could have a predictive value for identifying subjects at risk of dementia and to predict cognitive decline.

Objective: Search for relationships between the levels of some oxidative stress biomarkers and cognitive function decline that would help predict this decline.

Hydrocephalus due to extreme dilation of Virchow-Robin spaces.

Virchow-Robin spaces (VRS) are extensions of the subarachnoid space surrounding perforating blood vessels entering the brain parenchyma. VRS are fluid filled, but almost virtual and only visible on MRI of the brain when dilated. Such dilations are commonly asymptomatic.

Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone.

The hypocretin (orexin) system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1) and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867) and HCRTR2 (EMPA) antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat.

Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.

Trace amines (TAs) such as β-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons.

Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics.

Background: Trace amines, compounds structurally related to classical biogenic amines, represent endogenous ligands of the trace amine-associated receptor 1 (TAAR1). Because trace amines also influence the activity of other targets, selective ligands are needed for the elucidation of TAAR1 function. Here we report on the identification and characterization of the first selective and potent TAAR1 partial agonist.

A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight.

Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger serious side effects that precipitate treatment discontinuation.

Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by brain accumulation of amyloid-β peptide and neurofibrillary tangles, which are believed to initiate a pathological cascade that results in progressive impairment of cognitive functions and eventual neuronal death. To obtain a mouse model displaying the typical AD histopathology of amyloidosis and tauopathy, we generated a triple-transgenic mouse line (TauPS2APP) by overexpressing human mutations of the amyloid precursor protein, presenilin2 and tau genes. Stereological analysis of TauPS2APP mice revealed significant neurodegeneration of GABAergic septo-hippocampal projection neurons as well as their target cells, the GABAergic hippocampal interneurons.

Dimorphic effects of leptin on the circadian and hypocretinergic systems of mice.

The hormone leptin controls food intake and body weight through its receptor in the hypothalamus, and may modulate physiological functions such as reproduction, sleep or circadian timing. In the present study, the effects of leptin on the resetting of the circadian clock, the hypothalamic suprachiasmatic nucleus (SCN) and on the activity of the hypocretinergic system were examined in vivo, with comparative analysis between male and female mice. A single leptin injection (5 mg/kg) at both the onset and offset of the activity period did not alter locomotion of mice housed under a 12 : 12 h light/dark cycle and did not shift the circadian behavioral rhythm of mice housed in constant darkness.

Suspected acute coronary syndrome in a theater of operations: first management, medical evacuation, and final diagnosis: experience of the French Medical Army.

Objective: to evaluate the treatment of the acute coronary syndrome (ACS) among soldiers stationed on a theater of operations by structures usually conceived to treat combat-related trauma.

Methods: We performed a retrospective study involving the whole medical evacuations out of a theater of operations to the benefit of the French Armed forces, for a suspected diagnosis of ACS.

Results: 35 patients were included in this study with 20 for a diagnosis of persistent ST-Segment Elevation Myocardial Infarction (STEMI).

Melatonin controls seasonal breeding by a network of hypothalamic targets.

In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year.

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics.

[A myocardial infarction complicated with mitral anterior papillary muscle rupture during long-term corticotherapy].

The authors report anterolateral papillary muscle rupture, occurring in a 67-year-old patient admitted for acute coronary syndrome. Mitral regurgitation, a rare but dramatic complication of myocardial infarction, is most often a consequence of posterior papillary muscle rupture. The 'protection' of the anterior papillary muscle is associated with vascularization via a dual coronary artery supply.

Kisspeptin and the seasonal control of reproduction in hamsters.

Reproduction is a complex and energy demanding function. When internal and external conditions might impair reproductive success (negative energy balance, stress, harsh season) reproductive activity has to be repressed. Recent evidence suggests that these inhibitory mechanisms operate on Kiss1-expressing neurons, which were recently shown to be implicated in the regulation of GnRH release.

RFamide-related peptide gene is a melatonin-driven photoperiodic gene.

In seasonal species, various physiological processes including reproduction are organized by photoperiod via melatonin, but the mechanisms of melatonin action are still unknown. In birds, the peptide gonadotropin-inhibiting hormone (GnIH) has been shown to have inhibitory effects on reproductive activity and displays seasonal changes of expression. Here we present evidence in mammals that the gene orthologous to GnIH, the RFamide-related peptide (RFRP) gene, expressed in the mediobasal hypothalamus, is strongly regulated by the length of the photoperiod, via melatonin.

The circadian clock stops ticking during deep hibernation in the European hamster.

Hibernation is a fascinating, yet enigmatic, physiological phenomenon during which body temperature and metabolism are reduced to save energy. During the harsh season, this strategy allows substantial energy saving by reducing body temperature and metabolism. Accordingly, biological processes are considerably slowed down and reduced to a minimum.

[Cardiac toxicity of catecholamines. Report of two cases].

Introduction: The role of catecholamines in the cardiac expression of pheochromocytoma is well-known. The physiopathology of the syndrome of Tako-tsubo remains more unclear.

Exegesis: We describe 2 clinical cases of acute coronary syndrome with left ventricular dysfunction and no coronary artery stenosis.

[Increased secretion of Nt-proBNP immediately after percutaneous coronary intervention: about 90 cases].

Nt-proBNP have emerged as useful biomarker for the diagnosis and prognostic of heart failure but also recently in acute coronary syndrome. Myocardial ischemia is probably an important stimulus for Nt-proBNP release. Transient myocardial ischemia is inducing by balloon inflation during percutaneous coronary intervention (PCI).

Shedding light on circadian clock resetting by dark exposure: differential effects between diurnal and nocturnal rodents.

The master circadian clock in mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, is entrained by light and behavioural stimulation. In addition, the SCN can be reset by dark pulses in nocturnal rodents under constant light conditions. Here, the shifting effects of a dark pulse on the SCN clock were detailed at both a behavioural and molecular level in a nocturnal rodent (Syrian hamster), and were compared to those of a diurnal rodent (Arvicanthis ansorgei).

Kisspeptin: a key link to seasonal breeding.

In seasonal species, photoperiod (i.e. daylength) tightly regulates reproduction to ensure that birth occurs at the most favorable time of year.

Kisspeptin mediates the photoperiodic control of reproduction in hamsters.

The KiSS-1 gene encodes kisspeptin, the endogenous ligand of the G-protein-coupled receptor GPR54. Recent data indicate that the KiSS-1/GPR54 system is critical for the regulation of reproduction and is required for puberty onset. In seasonal breeders, reproduction is tightly controlled by photoperiod (i.

Differential expression of activator protein-1 proteins in the pineal gland of Syrian hamster and rat may explain species diversity in arylalkylamine N-acetyltransferase gene expression.

Species differences have been reported for the nighttime regulation of arylalkylamine N-acetyltransferase (AA-NAT), the melatonin rhythm-generating enzyme. In particular, de novo synthesis of stimulatory transcription factors is required for Aa-nat transcription in the Syrian hamster but not in the rat pineal gland. The present work investigated the contribution of phosphorylated cAMP-responsive element-binding protein, c-FOS, c-JUN, and JUN-B in the regulation of Aa-nat transcription in Syrian hamsters compared with rats.