Ischaemic Priapism and Glucose-6-Phosphate Dehydrogenase Deficiency: A Mechanism of Increased Oxidative Stress?

Ischaemic priapism is a devastating urological condition that has the potential to cause permanent erectile dysfunction. The disorder has been associated with numerous medical conditions and the use of pharmacotherapeutic agents. The aetiology is idiopathic in a number of cases.

Cyclic GMP balance is critical for malaria parasite transmission from the mosquito to the mammalian host.

Unlabelled: Transmission of malaria occurs during Anopheles mosquito vector blood meals, when Plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. Sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. While the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not been clearly delineated.

Parkinson's disease and enhanced inflammatory response.

Parkinson's disease (PD) is the first and second most prevalent motor and neurodegenerative disease, respectively. The clinical symptoms of PD result from a loss of midbrain dopaminergic (DA) neurons. However, the molecular cause of DA neuron loss remains elusive.

Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein.

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.

A Combination Therapy of 17β-Estradiol and Memantine Is More Neuroprotective Than Monotherapies in an Organotypic Brain Slice Culture Model of Traumatic Brain Injury.

Combination therapies are a promising therapeutic option for traumatic brain injury (TBI) owing to the clinical failure of monotherapy treatments, such as progesterone. Organotypic hippocampal slice cultures (OHSCs) from Sprague-Dawley rats were subjected to an in vitro TBI, and the neuroprotective effects of 17β-estradiol (E2) or memantine (MEM) monotherapies were quantified. Several combination treatments at different concentrations of both drugs were tested, with 100 pM of E2 and 10 μM of MEM statistically and significantly reducing cell death over either monotherapy when administered immediately after injury.

Predicting changes in cortical electrophysiological function after in vitro traumatic brain injury.

Finite element (FE) models of traumatic brain injury (TBI) are capable of predicting injury-induced brain tissue deformation. However, current FE models are not equipped to predict the biological consequences of tissue deformation, which requires the determination of tolerance criteria relating the effects of mechanical stimuli to biologically relevant functional responses. To address this deficiency, we present functional tolerance criteria for the cortex for alterations in neuronal network electrophysiological function in response to controlled mechanical stimuli.

Worn down nails after acrylic nail removal.

Worn-down nail syndrome is a nail disorder characterized by thinning of the distal nail plate caused by repetitive chemical or mechanical trauma. We present a previously undescribed source of worn-down nail syndrome caused by trauma from nail filing after acrylic nail removal.

The DNA-binding network of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20-30 s. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154 TFs.

Alterations in Hippocampal Network Activity after In Vitro Traumatic Brain Injury.

Traumatic brain injury (TBI) alters function and behavior, which can be characterized by changes in electrophysiological function in vitro. A common cognitive deficit after mild-to-moderate TBI is disruption of persistent working memory, of which the in vitro correlate is long-lasting, neuronal network synchronization that can be induced pharmacologically by the gamma-aminobutyric acid A antagonist, bicuculline. We utilized a novel in vitro platform for TBI research, the stretchable microelectrode array (SMEA), to investigate the effects of TBI on bicuculline-induced, long-lasting network synchronization in the hippocampus.

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons.

Molecular pathophysiology of priapism: emerging targets.

Priapism is an erectile disorder involving uncontrolled, prolonged penile erection without sexual purpose, which can lead to erectile dysfunction. Ischemic priapism, the most common of the variants, occurs with high prevalence in patients with sickle cell disease. Despite the potentially devastating complications of this condition, management of recurrent priapism episodes historically has commonly involved reactive treatments rather than preventative strategies.

Is testosterone deficiency a possible risk factor for priapism associated with sickle-cell disease?

Purpose: The purpose of this study was to determine the association of testosterone deficiency and priapism in adult men with sickle cell disease (SCD).

Methods: A cross-sectional study of 50 adult men with SCD (hemoglobin SS) was performed. All patients had early morning blood taken for total and free testosterone, FSH, LH, prolactin, lipid levels, LDH and hematological indices.

Mutual exacerbation of peroxisome proliferator-activated receptor γ coactivator 1α deregulation and α-synuclein oligomerization.

Objective: Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson disease (PD), with accumulating evidence that prefibrillar oligomers and protofibrils are the pathogenic species in PD and related synucleinopathies. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a key regulator of mitochondrial biogenesis and cellular energy metabolism, has recently been associated with the pathophysiology of PD. Despite extensive effort on studying the function of PGC-1α in mitochondria, no studies have addressed whether PGC-1α directly influences oligomerization of α-syn or whether α-syn oligomers impact PGC-1α expression.

An open-source toolbox for automated phenotyping of mice in behavioral tasks.

Classifying behavior patterns in mouse models of neurological, psychiatric and neurodevelopmental disorders is critical for understanding disease causality and treatment. However, complete characterization of behavior is time-intensive, prone to subjective scoring, and often requires specialized equipment. Although several reports describe automated home-cage monitoring and individual task scoring methods, we report the first open source, comprehensive toolbox for automating the scoring of several common behavior tasks used by the neuroscience community.

Let-7 coordinately suppresses components of the amino acid sensing pathway to repress mTORC1 and induce autophagy.

Macroautophagy (hereafter autophagy) is the major pathway by which macromolecules and organelles are degraded. Autophagy is regulated by the mTOR signaling pathway-the focal point for integration of metabolic information, with mTORC1 playing a central role in balancing biosynthesis and catabolism. Of the various inputs to mTORC1, the amino acid sensing pathway is among the most potent.

Functional tolerance to mechanical deformation developed from organotypic hippocampal slice cultures.

In this study, we measured changes in electrophysiological activity after mechanical deformation of living organotypic hippocampal brain slice cultures at tissue strains and strain rates relevant to traumatic brain injury (TBI). Electrophysiological activity was measured throughout the hippocampus with a 60-electrode microelectrode array. Electrophysiological parameters associated with unstimulated spontaneous activity (neural event firing rate, duration, and magnitude), stimulated evoked responses (the maximum response [Formula: see text], the stimulus current necessary for a half-maximal response [Formula: see text], and the electrophysiological parameter m that is representative of firing uniformity), and paired-pulse responses (paired-pulse ratio at varying interstimulus intervals) were quantified for each hippocampal region (CA1, CA3, and DG).

Current state of prostate cancer treatment in Jamaica.

Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide.

Brain-on-a-chip microsystem for investigating traumatic brain injury: Axon diameter and mitochondrial membrane changes play a significant role in axonal response to strain injuries.

Diffuse axonal injury (DAI) is a devastating consequence of traumatic brain injury, resulting in significant axon and neuronal degeneration. Currently, therapeutic options are limited. Using our brain-on-a-chip device, we evaluated axonal responses to DAI.

Significant head accelerations can influence immediate neurological impairments in a murine model of blast-induced traumatic brain injury.

Although blast-induced traumatic brain injury (bTBI) is well recognized for its significance in the military population, the unique mechanisms of primary bTBI remain undefined. Animate models of primary bTBI are critical for determining these potentially unique mechanisms, but the biomechanical characteristics of many bTBI models are poorly understood. In this study, we examine some common shock tube configurations used to study blast-induced brain injury in the laboratory and define the optimal configuration to minimize the effect of torso overpressure and blast-induced head accelerations.

Synergistic signaling of tumor cell invasiveness by hepatocyte growth factor and hypoxia.

Hepatocyte growth factor (HGF) signaling promotes tumor invasiveness in renal cell carcinoma (RCC) and other cancers. In clear cell RCC, VHL loss generates pseudohypoxia that exacerbates HGF-driven invasion through β-catenin deregulation. Hypoxia also enhances HGF-driven invasiveness by papillary RCC cells, but in the absence of VHL, loss signaling integration involves three parallel routes: 1) hypoxia-induced reactive oxygen species production and decreased DUSP2 expression, leading to enhanced mitogen-activated protein kinase (MAPK) cascade activation; 2) reactive oxygen species-induced diacylglycerol production by phospholipase Cγ, leading to protein kinase C activation and increased protein phosphatase- 2A activity, thereby suppressing HGF-induced Akt activation; and 3) a profound shift from HGF-enhanced, proliferation- oriented metabolism to autophagy-dependent invasion and suppression of proliferation.

GPR30 activation is neither necessary nor sufficient for acute neuroprotection by 17β-estradiol after an ischemic injury in organotypic hippocampal slice cultures.

In this study, we investigated the role of GPR30 in 17β-estradiol- (E2) mediated neuroprotection after an ischemic injury in an organotypic hippocampal slice culture (OHSC) model. We report that after oxygen-glucose deprivation (OGD), a physiological concentration of 100 pM E2 provided the greatest significant reduction in cell death while supra-physiological levels were less effective. The canonical estrogen receptor (ER) inhibitor ICI 182,780 completely abrogated the therapeutic effect of E2 while the GPR30 antagonist G-15 effected a slight but not significant reduction in neuroprotection.

Isolated primary blast alters neuronal function with minimal cell death in organotypic hippocampal slice cultures.

An increasing number of U.S. soldiers are diagnosed with traumatic brain injury (TBI) subsequent to exposure to blast.

Oxyphenisatin acetate (NSC 59687) triggers a cell starvation response leading to autophagy, mitochondrial dysfunction, and autocrine TNFα-mediated apoptosis.

Oxyphenisatin (3,3-bis(4-hydroxyphenyl)-1H-indol-2-one) and several structurally related molecules have been shown to have in vitro and in vivo antiproliferative activity. This study aims to confirm and extend mechanistic studies by focusing on oxyphenisatin acetate (OXY, NSC 59687), the pro-drug of oxyphenisatin. Results confirm that OXY inhibits the growth of the breast cancer cell lines MCF7, T47D, HS578T, and MDA-MB-468.

The mechanics of traumatic brain injury: a review of what we know and what we need to know for reducing its societal burden.

Traumatic brain injury (TBI) is a significant public health problem, on pace to become the third leading cause of death worldwide by 2020. Moreover, emerging evidence linking repeated mild traumatic brain injury to long-term neurodegenerative disorders points out that TBI can be both an acute disorder and a chronic disease. We are at an important transition point in our understanding of TBI, as past work has generated significant advances in better protecting us against some forms of moderate and severe TBI.