Electromyographic assessment of paratonia.

Many years after its initial description, paratonia remains a poorly understood concept. It is described as the inability to relax muscles during muscle tone assessment with the subject involuntary facilitating or opposing the examiner. Although related to cognitive impairment and frontal lobe function, the underlying mechanisms have not been clarified.

Repetitive Transcranial Magnetic Stimulation as a Novel Therapy in Animal Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) in humans causes a broad range of structural damage and functional deficits due to both primary and secondary injury mechanisms. Over the past three decades, animal models have been established to replicate the diverse changes of human TBI, to study the underlying pathophysiology and to develop new therapeutic strategies. However, drugs that were identified as neuroprotective in animal brain injury models were not successful in clinical trials phase II or phase III.

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury.

Background: Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement.

Longitudinal Changes in the Motor Learning-Related Brain Activation Response in Presymptomatic Huntington's Disease.

Neurocognitive decline, including deficits in motor learning, occurs in the presymptomatic phase of Huntington's disease (HD) and precedes the onset of motor symptoms. Findings from recent neuroimaging studies have linked these deficits to alterations in fronto-striatal and fronto-parietal brain networks. However, little is known about the temporal dynamics of these networks when subjects approach phenoconversion.

Sleep reverts changes in human gray and white matter caused by wake-dependent training.

Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity.

Cognitive processess and cognitive reserve in multiple sclerosis.

Multiple Sclerosis (MS) is characterized by motor, cognitive, and neuropsychiatric symptoms, which can occur independently. While MS is traditionally considered an inflammatory disease of the white matter, degeneration of gray matter is increasingly recognized as an important contributor to the progressive cognitive decline. A protective factor against the progression of cognitive dysfunction in MS could be the cognitive reserve, defined as resistance to brain dysfunction.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications.

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses.

Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia.

Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand-induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the binding of a nonhydrolyzable GTP analogue [(35)S]GTPγS binding to specific G protein subtypes in response to odorants, dopamine, or serotonin in ON cell membranes from matched schizophrenia-control subjects.

Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling.

Colorectal cancer (CRC) is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB) is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy.

The dual role of iNOS in cancer.

Nitric oxide (NO) is one of the 10 smallest molecules found in nature. It is a simple gaseous free radical whose predominant functions is that of a messenger through cGMP. In mammals, NO is synthesized by the enzyme nitric oxide synthase (NOS) of which there are three isoforms.

Synthesis and anti-cancer potential of the positional isomers of NOSH-aspirin (NBS-1120) a dual nitric oxide and hydrogen sulfide releasing hybrid.

We recently reported the synthesis of NOSH-aspirin, a novel hybrid compound capable of releasing both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e.

Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e.

NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties.

Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses.

NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain.

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain.

NOSH-Aspirin Inhibits Colon Cancer Cell Growth: Effects Of Positional Isomerism.

Background: NOSH-aspirin, a novel hybrid that releases nitric oxide (NO) and hydrogen sulfide (HS) was designed to overcome the potential side effects of aspirin.

Aim: We compared the cell growth inhibitory properties of ortho-, meta-, and para-NOSH-aspirins. Effects of electron donating/withdrawing groups on the stability and biological activity of these novel compounds were also evaluated.

Utility Of Nitric Oxide And Hydrogen Sulfide-Releasing Chimeras As Anticancer Agents.

Background: Aspirin is chemopreventive but has significant side effects. We developed NOSH-aspirin a safer, nitric oxide and hydrogen sulfide releasing hybrid.

Aim: Here we report on NOSH-aspirin as an anti-inflammatory and its effects on human cancer cell kinetics and various cancer xenografts.

Nitric Oxide-Releasing Aspirin Suppresses NF-κB Signaling in Estrogen Receptor Negative Breast Cancer Cells in Vitro and in Vivo.

Estrogen receptor negative (ER(-)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(-) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(-) breast cancers.

Orbitofrontal (18) F-DOPA Uptake and Movement Preparation in Parkinson's Disease.

In Parkinson's disease (PD) degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD.

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach.

Background: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions.

Methods: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs.

Neural and behavioral correlates of extended training during sleep deprivation in humans: evidence for local, task-specific effects.

Recent work has demonstrated that behavioral manipulations targeting specific cortical areas during prolonged wakefulness lead to a region-specific homeostatic increase in theta activity (5-9 Hz), suggesting that theta waves could represent transient neuronal OFF periods (local sleep). In awake rats, the occurrence of an OFF period in a brain area relevant for behavior results in performance errors. Here we investigated the potential relationship between local sleep events and negative behavioral outcomes in humans.

Src kinase as a mediator of convergent molecular abnormalities leading to NMDAR hypoactivity in schizophrenia.

Numerous investigations support decreased glutamatergic signaling as a pathogenic mechanism of schizophrenia, yet the molecular underpinnings for such dysregulation are largely unknown. In the post-mortem dorsolateral prefrontal cortex (DLPFC), we found striking decreases in tyrosine phosphorylation of N-methyl-D aspartate (NMDA) receptor subunit 2 (GluN2) that is critical for neuroplasticity. The decreased GluN2 activity in schizophrenia may not be because of downregulation of NMDA receptors as MK-801 binding and NMDA receptor complexes in postsynaptic density (PSD) were in fact increased in schizophrenia cases.

Intensive rehabilitation treatment in early Parkinson's disease: a randomized pilot study with a 2-year follow-up.

Background: Although physical exercise improves motor aspects of Parkinson's disease (PD), it is not clear whether it may also have a neuroprotective effect. Objective. In this 2-year follow-up study, we determined whether intensive exercise in the early stages of the disease slows down PD progression.

Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq Proteins.

Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21) prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX) and hippocampus.