85 research outputs found
A comparison of early and late treatments on allodynia and its chronification in experimental neuropathic pain
SEPARATION AND IDENTIFICATION OF MICROFIBERS IN THE WASTEWATERS OF TEXTILE FINISHING PROCESS
Microplastic pollution is a major global issue, with the textile industry responsible for 35% of the microplastics (MPs) released as microfibers (MFs). Due to their small size, MPs can interact with a wide range of organisms and lead to chromosomal mutations that cause obstruction, inflammation, and organ accumulation. This study aims to detect and separate MFs released from the textile finishing machinery, which is used to give a soft touch to fabrics. Before being transferred to the effluent water, the wastewater samples taken from the section were pretreated with 15% H2O2 at 25 °C for 5 days, and then MFs were captured by a filter. Filters with accumulated MFs were observed using a light microscope, and a micro-FTIR was used to detect MFs chemically. The main results showed that acrylic and cotton MFs were detected in wastewater, and wastewater samples from different dates contained 0.058 g/L and 0.251 g/L MFs which reveals the seriousness of the MP problem we are facing
THE EFFECT OF POLYMER TYPE AND FIBER ORIENTATION ON THE COMPLIANCE PROPERTIES OF ELECTROSPUN VASCULAR GRAFTS
Vascular diseases are a major source of fatalities globally. However, the lack of accessibility of autologous vessels and the poor efficacy of commercial small-diameter vascular grafts limit surgical alternatives. Researchers therefore aimed to develop vascular prostheses that meet all requirements. Apart from the benefits of tissue-engineered grafts, significant obstacles that still hinder successful grafting include compliance mismatch, dilatation, thrombus development, and the absence of elastin. Among these issues, compliance mismatch between native vessel and artificial vascular scaffold has been mentioned in the literature as a possible cause of intimal hyperplasia, suture site rupture and endothelial and platelet cell damage. As a result, the usage of suitable materials and optimized fabrication techniques are required to achieve better control over the characteristics and functionality of the grafts. In particular, in the case of electrospun vascular grafts, the compliance can be adjusted throughout a broad range of values by adjusting the electrospinning parameters such as material selection, fiber orientation, porosity, and wall thickness. In this study, the electrospun vascular grafts consisting of pure PCL, PLA, and their blends were produced by using two different rotation speeds to achieve the oriented and non-oriented scaffolds. The impact of polymer type and fiber orientation on the compliance properties was evaluated. The results revealed that both material selection and fiber alignment have a significant effect on the compliance levels. PCL100_R grafts had the highest compliance value whereas the PCLPLA50_O scaffold had the lowest
A PRELIMINARY STUDY EXAMINING THE BURST STRENGTH OF VASCULAR TUBULAR SCAFFOLDS
In this study, neat PCL, neat PLA and PLA/PCL (50/50) based tubular surfaces are produced by electrospinning to simulate the native blood vessel structure and to investigate the effects of both graft material and fiber orientation on burst strength. The burst pressure values of these vascular graft structures that designed with both randomly oriented fibers and oriented fibers, measured by a custom- burst pressure tester, and the results are compared. The results show that fiber orientation have a great influence on burst pressure, regardless of the type of biomaterial. It is determined that grafts with oriented fibers have at least twice the burst strength than those with random fibers. The findings indicate that changing the graft material has also an effect on burst strength. When the results are analyzed by polymer type, although the PLA100_O sample has the highest burst strength among all oriented fiber sample groups, it is better to determine the vascular graft candidate by taking into account radial elasticity
How does disease location affect acute phase reactants in ulcerative colitis?
Background: We aimed to evaluate erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell (WBC), platelet (PLT) counts and albumin levels according to disease location in ulcerative colitis.Methods: The ESR, CRP, WBC, PLT counts and albumin levels of 206 ulcerative colitis patients with endoscopic activity were retrospectively evaluated. Endoscopic activity had been assessed using Rachmilewitz endoscopic activity index. Patients were grouped according to the extent of disease by Montreal classification, and they were evaluated regarding the location and severity of disease according to the laboratory test results.Results: Among 206 patients, 88 (42.7%) had extensive colitis, 89 (43.2%) of them had left sided colitis and 29 (14%) patients had proctitis. According to the endoscopic activity index, 32.04% of the patients had mild activity, 39.32% moderate activity and 28.64% had severe activity. As the disease extent progressed from the distal to the proximal intestine, CRP, ESR, WBC and PLT counts showed a significant increase while albumin levels showed a significant decrease. In our study, the test that yielded the best results in the assessment of disease activity was CRP, which was found to be high in 80% of patients with extensive colitis, followed by ESR, PLT and WBC counts. As the involved intestine shortened, the rate of patients with abnormal laboratory tests significantly decreasedConclusion: CRP, ESR, WBC, PLT counts and albumin levels are of limited value in determining disease activity in ulcerative colitis patients, especially in those with proctiti
Cortical Excitability and Activation of TrkB Signaling During Rebound Slow Oscillations Are Critical for Rapid Antidepressant Responses
Rapid antidepressant effects of ketamine become most evident when its psychotomimetic effects subside, but the neurobiological basis of this lag remains unclear. Laughing gas (N2O), another NMDA-R (N-methyl-d-aspartate receptor) blocker, has been reported to bring antidepressant effects rapidly upon drug discontinuation. We took advantage of the exceptional pharmacokinetic properties of N2O to investigate EEG (electroencephalogram) alterations and molecular determinants of antidepressant actions during and immediately after NMDA-R blockade. Effects of the drugs on brain activity were investigated in C57BL/6 mice using quantitative EEG recordings. Western blot and qPCR were used for molecular analyses. Learned helplessness (LH) was used to assess antidepressant-like behavior. Immediate-early genes (e.g., bdnf) and phosphorylation of mitogen-activated protein kinasemarkers of neuronal excitabilitywere upregulated during N2O exposure. Notably, phosphorylation of BDNF receptor TrkB and GSK3 (glycogen synthase kinase 3) became regulated only gradually upon N2O discontinuation, during a brain state dominated by slow EEG activity. Subanesthetic ketamine and flurothyl-induced convulsions (reminiscent of electroconvulsive therapy) also evoked slow oscillations when their acute pharmacological effects subsided. The correlation between ongoing slow EEG oscillations and TrkB-GSK3 signaling was further strengthened utilizing medetomidine, a hypnotic-sedative agent that facilitates slow oscillations directly through the activation of (2)-adrenergic autoreceptors. Medetomidine did not, however, facilitate markers of neuronal excitability or produce antidepressant-like behavioral changes in LH. Our results support a hypothesis that transient cortical excitability and the subsequent regulation of TrkB and GSK3 signaling during homeostatic emergence of slow oscillations are critical components for rapid antidepressant responses.Peer reviewe
Peripheral Delta Opioid Receptors Mediate Formoterol Anti-allodynic Effect in a Mouse Model of Neuropathic Pain.
Neuropathic pain is a challenging condition for which current therapies often remain unsatisfactory. Chronic administration of β2 adrenergic agonists, including formoterol currently used to treat asthma and chronic obstructive pulmonary disease, alleviates mechanical allodynia in the sciatic nerve cuff model of neuropathic pain. The limited clinical data currently available also suggest that formoterol would be a suitable candidate for drug repurposing. The antiallodynic action of β2 adrenergic agonists is known to require activation of the delta-opioid (DOP) receptor but better knowledge of the molecular mechanisms involved is necessary. Using a mouse line in which DOP receptors were selectively ablated in neurons expressing Nav1.8 sodium channels (DOP cKO), we showed that these DOP peripheral receptors were necessary for the antiallodynic action of the β2 adrenergic agonist formoterol in the cuff model. Using a knock-in mouse line expressing a fluorescent version of the DOP receptor fused with the enhanced green fluorescent protein (DOPeGFP), we established in a previous study, that mechanical allodynia is associated with a smaller percentage of DOPeGFP positive small peptidergic sensory neurons in dorsal root ganglia (DRG), with a reduced density of DOPeGFP positive free nerve endings in the skin and with increased DOPeGFP expression at the cell surface. Here, we showed that the density of DOPeGFP positive free nerve endings in the skin is partially restored and no increase in DOPeGFP translocation to the plasma membrane is observed in mice in which mechanical pain is alleviated upon chronic oral administration of formoterol. This study, therefore, extends our previous results by confirming that changes in the mechanical threshold are associated with changes in peripheral DOP profile. It also highlights the common impact on DOP receptors between serotonin noradrenaline reuptake inhibitors such as duloxetine and the β2 mimetic formoterol.journal article20192020 02 14importe
Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein
Background
Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus.
Results
We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic cells, yet its function is not understood. Here, we find MVP expression highly specific to the limbic system and show that Mvp regulates neuronal morphology, postnatally and specifically in males. We also recapitulate a previously reported genetic interaction and show that Mvp+/−;Mapk3+/− mice exhibit behavioral deficits, notably decreased anxiety-like traits detected in the elevated plus maze and open field paradigms.
Conclusions
Our study highlights multiple gene drivers in neuroanatomical phenotypes, interacting with each other through complex relationships. It also provides the first evidence for the involvement of the major vault protein in the regulation of brain size and neuroanatomy, specifically in male mice
Isoflurane produces antidepressant effects and induces TrkB signaling in rodents
A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3 beta (GSK3 beta). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.Peer reviewe
The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system.
BACKGROUND: Clinical management of neuropathic pain, which is pain arising as a consequence of a lesion or a disease affecting the somatosensory system, partly relies on the use of anticonvulsant drugs such as gabapentinoids. Therapeutic action of gabapentinoids such as gabapentin and pregabalin, which act by the inhibition of calcium currents through interaction with the α2δ-1 subunit of voltage-dependent calcium channels, is well documented. However, some aspects of the downstream mechanisms are still to be uncovered. Using behavioral, genetic, and pharmacological approaches, we tested whether opioid receptors are necessary for the antiallodynic action of acute and/or long-term pregabalin treatment in the specific context of neuropathic pain.
RESULTS: Using the cuff model of neuropathic pain in mice, we show that acute pregabalin administration at high dose has a transitory antiallodynic action, while prolonged oral pregabalin treatment leads to sustained antiallodynic action, consistent with clinical observations. We show that pregabalin remains fully effective in μ-opioid receptor, in δ-opioid receptor and in κ-opioid receptor deficient mice, either female or male, and its antiallodynic action is not affected by acute naloxone. Our work also shows that long-term pregabalin treatment suppresses tumor necrosis factor-α overproduction induced by sciatic nerve constriction in the lumbar dorsal root ganglia.
CONCLUSIONS: We demonstrate that neither acute nor long-term antiallodynic effect of pregabalin in a context of neuropathic pain is mediated by the endogenous opioid system, which differs from opioid treatment of pain and antidepressant treatment of neuropathic pain. Our data are also supportive of an impact of gabapentinoid treatment on the neuroimmune aspect of neuropathic pain.journal articleresearch support, non-u.s. gov't20162016 03 29importe
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