Emerging Roles of Sirtuins in Ischemic Stroke

Abstract

Ischemic stroke is one of the leading causes of death worldwide. It is characterized by a sudden disruption of blood flow to the brain causing cell death and damage, which will lead to neurological impairments. In the current state, only one drug is approved to be used in clinical setting and new therapies that confer ischemic neuroprotection are desperately needed. Several targets and pathways have been indicated to be neuroprotective in ischemic stroke, among which the sirtuin family of nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases has emerged as important modulators of several processes in the normal physiology and pathological conditions such as stroke. Recent studies have identified some members of the sirtuin family are able to ameliorate the devastating consequences of ischemic stroke by conferring neuroprotection by means of reducing neuronal cell death, oxidative stress, and neuroinflammation whereas some sirtuins are found to be detrimental in the pathophysiology of ischemic stroke. This review summarizes implications of sirtuins in ischemic stroke and the experimental evidences that demonstrate the potential of sirtuin modulators as neuroprotective therapy for ischemic stroke.

http://ift.tt/2sYeC73

Is the Personal Identity Debate a “Threat” to Neurosurgical Patients? A Reply to Müller et al.

Abstract

In their article in this journal, Sabine Müller, Merlin Bittlinger, and Henrik Walter launch a sweeping attack against what they call the "personal identity debate" as it relates to patients treated with deep brain stimulation (DBS). In this critique offered by Müller et al., the personal identity debate is said to: (a) be metaphysical in a problematic way, (b) constitute a threat to patients, and (c) use "vague" and "contradictory" statements from patients and their families as direct evidence for metaphysical theories. In this response, I critically evaluate Müller et al.'s argument, with a special focus on these three just-mentioned aspects of their discussion. My conclusion is that Müller et al.'s overall argument is problematic. It overgeneralizes criticisms that may apply to some, but certainly not to all, contributions to what they call the personal identity-debate. Moreover, it rests on a problematic conception of what much of this debate is about. Nor is Müller et al.'s overall argument fair in its assessment of the methodology used by most participants in the debate. For these reasons, we should be skeptical of Müller et al.'s claim that the "personal identity debate" is a "threat to neurosurgical patients".

http://ift.tt/2sNSUEF

Indications and outcomes for tunneled central venous line placement via the axillary vein in children

Abstract

Purpose

To assess the indications, safety and outcomes of tunneled central venous catheters (CVCs) placed via a cutdown approach into the axillary vein in children, an approach not well described in this population.

Methods

A retrospective cohort study was performed on pediatric patients who received CVCs via open cannulation of the axillary vein or one of its tributaries between January 2006 and October 2016 at two hospitals.

Results

A total of 24 axillary CVCs were placed in 20 patients [10 male (42%); mean weight 7.0 kg (SD 2.9); mean age 10 months (SD 6)]. The most common indications for axillary vein access included neck or chest wall challenges (tracheostomies or chest wall wounds) (n = 18). The median duration of line placement was 140 days (IQR 146). The most common indications for removal were completion of therapy (n = 7, 39%) and infection (n = 5, 28%). There were no early complications. Long-term complications included infection (n = 5) or catheter malfunction (n = 3).

Conclusions

Tunneled CVC placement via a cutdown approach into the axillary vein or its tributary can be an effective alternative approach to obtain long-term vascular access in children. Outcomes may be comparable to lines placed in traditional internal jugular and subclavian vein locations.

http://ift.tt/2sNihpQ

Retention and Transport of PAH-Degrading Bacterium Herbaspirillum chlorophenolicum FA1 in Saturated Porous Media Under Various Physicochemical Conditions

Abstract

Dispersal of functional microorganisms is a rate-limiting process during in situ bioremediation of contaminated soil and groundwater. In this work, series of column experiments were conducted to investigate the retention and transport behaviors of Herbaspirillum chlorophenolicum FA1, a promising bacterial agent for bioremediation, in saturated porous media under conditions of different combinations of grain size, solution pH, solution ionic strength (IS), and humic acid (HA) concentration. Experimental data showed that the mobility of FA1 in saturated porous media was strongly dependent on the physicochemical conditions. The breakthrough curves (BTCs) indicated that the amounts of FA1 in the effluent increased with increasing in sand size, solution pH, and HA concentration, but decreased with increase of solution IS. The shape of retention profiles (RPs) was hyper-exponential. The amounts of retained bacteria in the media also varied with the experimental conditions with opposite trends to that of effluent. Both experimental BTCs and RPs were simulated by a mathematical model that accounted for deposition kinetics to better interpret the effects of physicochemical conditions on FA1 deposition dynamics. Findings from this study showed that fate and transport of the functional bacterium FA1 in porous media strongly relied on the environmental conditions. Both experimental and modeling results can provide guidelines for field application of functional bacteria for soil and groundwater remediation.

http://ift.tt/2siYB9P

Action of three bioavailable antioxidants in orbital fibroblasts from patients with Graves’ orbitopathy (GO): a new frontier for GO treatment?

Abstract

Objective

Oxidative stress is involved in the pathogenesis of Graves' orbitopathy (GO) and an antioxidant approach has been advocated for GO treatment. Here, we investigated the action of three antioxidants in orbital fibroblasts, namely, vitamin C, N-acetyl-l-cysteine, and melatonin.

Methods

Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H₂O₂ to induce oxidative stress. Cell vitality assays were performed to determine the non-cytotoxic dose of each antioxidant. The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, cell proliferation, hyaluronic acid (HA), TNFα, IFNγ, and IL1β.

Results

H₂O₂ induced oxidative stress (augmented GSSG), increased cell proliferation as well as cytokine release, but did not affect HA release. All of the three antioxidant substances reduced H₂O₂-dependent oxidative stress. Vitamin C reduced proliferation in GO, but not in control fibroblasts. N-acetyl-l-cysteine reduced proliferation and IFNγ in GO, and HA and IL1β in both GO and control fibroblasts. Melatonin reduced IL1β and HA in GO and control fibroblasts, and IFNγ only in GO fibroblasts.

Conclusions

Our study provides evidence in support of an antioxidant role of vitamin C, N-acetyl-l-cysteine and melatonin in orbital fibroblasts. Some of the effects of these compounds are exclusive to GO fibroblasts, whereas some other are observed also in control fibroblasts. Our observations provide a basis for a possible clinical use of these substances in patients with GO.

http://ift.tt/2siVJdf

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Abstract

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter–nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

http://ift.tt/2sXj4TA

Bedeutung neuronaler Netzwerke für die motorische Rehabilitation nach einem Schlaganfall

Zusammenfassung

In Europa treten jährlich ca. 1,5 Mio. neue Schlaganfälle auf. Trotz der Weiterentwicklung der Akutbehandlung mit flächendeckenden Stroke-Units, Thrombolyse und Thrombektomie und der postakuten Neurorehabilitation erholt sich immer noch nur ein nicht zufriedenstellender Anteil der Patienten bis zu einem Grad, der ihnen erlaubt, sich wieder in ihr normales Leben zu integrieren. Der Schlaganfall ist damit der Hauptgrund für Langzeitbehinderung mit den entsprechenden persönlichen und gesundheitsökonomischen Konsequenzen. Daher müssen die Konzepte der Neurorehabilitation erweitert werden, um den Effekt von Neurorehabilitation zu erhöhen. Um dies zu erreichen, müssen das Verständnis zur Prädiktion des Erholungsverlaufes, die Mechanismen funktioneller Erholung, Faktoren, die Erholung beeinflussen, und eine darauf basierende Präzisionsmedizin verbessert werden. Zentral hierfür ist Schlaganfall als eine Erkrankung zu sehen, die nicht nur das geschädigte Areal beeinflusst, sondern das damit verbundene Netzwerk. Dies ist von entscheidender Bedeutung für das schlaganfallinduzierte Defizit, aber auch für die Prädiktion der Erholung und zur Bestimmung von Optionen für interventionelle Therapiestrategien, die in diesem Netzwerk an unterschiedlichsten Stellen (z. B. primär motorischer Kortex, sekundär motorische Areale) angreifen können. Der Beitrag diskutiert die Bedeutung von Netzwerkveränderungen für motorische Neurorehabilitation nach einem Schlaganfall und beschreibt, welche Konsequenzen und Optionen hieraus für die Neurorehabilitation entstehen können.

http://ift.tt/2sWZyH7