Thoracic endovascular repair of a ruptured thoracic aortic aneurysm with in situ laser fenestration of the left subclavian and left common carotid artery.

Most thoracic aortic aneurysms (TAAs) are asymptomatic and often diagnosed at the time of rupture. TAAs involving the proximal arch require adequate coverage with thoracic endovascular aortic repair, which is timely and challenging in emergent ruptures. In situ laser fenestration is a novel method of arch revascularization.

Ten-year trends in traumatic injury mechanisms and outcomes: A trauma registry analysis.

Background: The Oklahoma Trauma Registry (OTR) collects data from all state-licensed acute care hospitals. This study investigates trends and outcomes of trauma in Oklahoma using OTR.

Methods: 107,549 patients (2005-2014) with major severity and one of the following criteria were included: length of hospital stay ≥48 h, dead on arrival or death in the hospital, hospital transfer, ICU admission, or surgery on the head, chest, abdomen, or vascular system.

Glutamine triggers long-lasting increase in striatal network activity in vitro.

Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia.

Is it ethical to heal a young white elephant from his physiological autism?

Forty years ago a causal therapy of autism was offered which has never been tried out by the therapeutic profession. It predictably is so effective that even members of other mirror-competent bonding species can be healed from their "physiological autism." Niklas Luhmann belonged to the therapy's supporters and Leo Szilard had anticipated it in fiction 30 years earlier.

High-frequency voltage oscillations in cultured astrocytes.

Because of their close interaction with neuronal physiology, astrocytes can modulate brain function in multiple ways. Here, we demonstrate a yet unknown astrocytic phenomenon: Astrocytes cultured on microelectrode arrays (MEAs) exhibited extracellular voltage fluctuations in a broad frequency spectrum (100-600 Hz) after electrical stimulation. These aperiodic high-frequency oscillations (HFOs) could last several seconds and did not spread across the MEA.

Freshly frozen E18 rat cortical cells can generate functional neural networks after standard cryopreservation and thawing procedures.

Primary dissociated brain tissue from rodents is widely used in a variety of different scientific methods to investigate cellular processes in vitro. Often, for this purpose cell cultures need to be generated just on time, requiring extensive animal lab infrastructure. We show here that cryopreservation and thawing of dissociated tissue from rat cerebral cortex at embryonic day 18 is feasible without affecting its ability to form functional neuronal networks in vitro.

Benzodiazepine-site pharmacology on GABAA receptors in histaminergic neurons.

Background And Purpose: The histaminergic tuberomamillary nucleus (TMN) of the posterior hypothalamus controls the cognitive aspects of vigilance which is reduced by common sedatives and anxiolytics. The receptors targeted by these drugs in histaminergic neurons are unknown. TMN neurons express nine different subunits of the GABAA receptor (GABAA R) with three α- (α1, α2 and α5) and two γ- (γ1, γ 2) subunits, which confer different pharmacologies of the benzodiazepine-binding site.

The bile steroid chenodeoxycholate is a potent antagonist at NMDA and GABA(A) receptors.

The bile steroids (BS) cholic acid and chenodeoxycholic acid are produced in hepatocytes and in the brain. Nothing is known about neuronal actions of BS. Deficiency in a 27-hydroxylase enzyme coincides with reduced production of chenodeoxycholic acid (CDCA) and a relative increase in cholic acid in an inherited lipid storage disease, cerebrotendinous xanthomatosis, characterized by neurological dysfunctions, which can be treated by dietary CDCA.

GABAA receptors involved in sleep and anaesthesia: β1- versus β3-containing assemblies.

The histaminergic neurons of the posterior hypothalamus (tuberomamillary nucleus-TMN) control wakefulness, and their silencing through activation of GABA(A) receptors (GABA(A)R) induces sleep and is thought to mediate sedation under propofol anaesthesia. We have previously shown that the β1 subunit preferring fragrant dioxane derivatives (FDD) are highly potent modulators of GABA(A)R in TMN neurons. In recombinant receptors containing the β3N265M subunit, FDD action is abolished and GABA potency is reduced.

Fragrant dioxane derivatives identify beta1-subunit-containing GABAA receptors.

Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD).

Developmental alterations of DHPG-induced long-term depression of corticostriatal synaptic transmission: switch from NMDA receptor-dependent towards CB1 receptor-dependent plasticity.

In animal models of early Parkinson's disease (PD), motor deficits are accompanied by excessive striatal glutamate release. Blockade of group I metabotropic glutamate receptors (mGluRs), endocannabinoid degradation and nitric oxide (NO) synthesis combats PD symptoms. Activation of group I mGluRs with the specific agonist 3,5-dihydroxyphenylglycine (DHPG) induces long-term depression of corticostriatal transmission (LTD(DHPG)) in the adult mouse striatum requiring NO synthesis downstream to cannabinoid CB1 receptor (CB1R) activation suggesting a dual role for LTD(DHPG): neuroprotective by down-regulation of glutamatergic transmission and, under certain circumstances, neurotoxic by release of NO.

A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

Background: Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised, double-blinded study evaluated the analgesic efficacy of prolonged-release (PR) oral oxycodone when co-administered with PR oral naloxone, and its impact on opioid-induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone.

Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.

Unlabelled: This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain.

Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain.

Background And Objectives: Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged-release (PR) oxycodone when co-administered with oral naloxone PR.

Methods: Two hundred and two patients with chronic cancer- or non-cancer-related pain undergoing stable oxycodone PR therapy (40, 60 or 80 mg/day) were randomised to one of four intervention groups: 10, 20 or 40 mg/day naloxone PR or placebo.

GABAA-receptor modification in taurine transporter knockout mice causes striatal disinhibition.

The Striatum is involved in the regulation of movements and motor skills. We have shown previously, that the osmolyte and neuromodulator taurine plays a role in striatal plasticity. We demonstrate now that hereditary taurine deficiency in taurine-transporter knock-out (TAUT KO) mice results in disinhibition of striatal network activity, which can be corrected by taurine supplementation.

Development and pharmacological modulation of embryonic stem cell-derived neuronal network activity.

Embryonic stem cells can be differentiated into neurons of diverse neurotransmitter-specific phenotypes. While the time course of functional progression of ES cell-derived neural precursors towards mature neurons has been described in detail on single-cell level, the temporal development and pharmacological modulation of ES cell-derived neuronal network activity have not been explored yet. Neuronal network activity can be assessed by the microelectrode array (MEA) technology that allows simultaneous monitoring of the electrical activity exhibited by entire populations of neurons over several weeks or months in vitro.

[Efficacy of treatment with Repithel and Jelonet in comparison to treatment with Jelonet alone - a randomized clinical trial in patients receiving meshed skin grafts].

Unlabelled: Moist wound treatment is a well recognized method for the treatment of aseptic acute and chronic wounds. While the moist environment is beneficial to the woundhealing process, it also increases the risk of bacterial superinfection. We here report on the results of a clinical phase-III-study in which we tested the effect of a new PVP-iodine liposomal hydrogel (Repithel) on split-thickness skin grafts.

P2Y receptor-mediated excitation in the posterior hypothalamus.

Histaminergic neurons located in the posterior hypothalamus (tuberomamillary nucleus, TMN) project widely through the whole brain controlling arousal and attention. They are tonically active during wakefulness but cease firing during sleep. As a homeostatic theory of sleep involves ATP depletion and adenosine accumulation in the brain, we investigated the role of ATP and its analogues as well as adenosine on neuronal activity in the TMN.

PVP-iodine in hydrosomes and hydrogel--a novel concept in wound therapy leads to enhanced epithelialization and reduced loss of skin grafts.

Background: Moist wound treatment improves healing at a possibly increased risk of bacterial infection and many local antiseptics impair healing. A moist treatment modality with efficient antimicrobial activity would be desirable.

Methods: In this monocentric, randomized, observer blinded, phase III study, a new hydrosome polyvinyl-pyrrolidone (PVP)-iodine preparation in hydrogel containing iodine in a 3% concentration (Repithel) was investigated for its effect on epithelialization in patients receiving meshed skin grafts.

Repithel: removing the barriers to wound healing.

Background: Various standardized and/or validated models exist to test wound healing products. This article discusses their usefulness in clinical practice.

Objectives: Major barriers to wound healing have been identified after intense interaction of research and practitioners.

Neuronal network properties of human teratocarcinoma cell line-derived neurons.

Understanding the structural and functional development of neurons in networks has a high impact to estimate the potentials for restorative therapies. Neurons derived from the human NT2 cell line (hNT) formed networks with a clustered neuritic architecture in vitro, whereas primary dissociated embryonic rat cortical neurons (Cx) displayed a more homogenous cell assembly. Spontaneous spikes of both cell types were recorded on microelectrode arrays within 2 weeks after seeding, but hNT showed a mostly uncorrelated firing pattern in contrast to Cx with highly synchronized bursting.

Implications for hyperhomocysteinemia: not homocysteine but its oxidized forms strongly inhibit neuronal network activity.

Severe hyperhomocysteinemia (50-200 microM) often presents itself with acute neuronal dysfunction including seizures and psychosis. Its moderate form (15-50 microM) is associated with cognitive impairment and dementia. We investigated the neuropharmacological effects of homocysteine and its oxidized forms, homocysteinesulfinic acid (HCSA) and homocysteic acid (HCA), on neuronal network function utilizing dissociated cortical neurons from embryonic Wistar rats on microelectrode arrays.

Cryopreserved rat cortical cells develop functional neuronal networks on microelectrode arrays.

Neurons growing on microelectrode arrays (MEAs) are promising tools to investigate principal neuronal network mechanisms and network responses to pharmaceutical substances. However, broad application of these tools, e.g.

Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed.