Search results for: membrane receptor

Authors: Oranso T. Mahlangi, Bhekie B. Mamba

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The occurrence of trace organic compounds (TOrCs) in water has raised health concerns for living organisms. The majority of TorCs, including pharmaceuticals and volatile organic compounds, are poorly monitored, partly due to the high cost of analysis and less strict water quality guidelines in South Africa. Therefore, the removal of TorCs is important to guarantee safe potable water. In this study, ZnO nanoparticles were fabricated in situ in polyethersulfone (PES) polymer solutions. This was followed by membrane synthesis using the phase inversion technique. Techniques such as FTIR, Raman, SEM, AFM, EDS, and contact angle measurements were used to characterize the membranes for several physicochemical properties. The membranes were then evaluated for their efficiency in treating pharmaceutical wastewater and resistance to organic (sodium alginate) and protein (bovine serum albumin) fouling. EDS micrographs revealed uniform distribution of ZnO nanoparticles within the polymer matrix, while SEM images showed uniform fingerlike structures. The addition of ZnO increased membrane roughness as well as hydrophilicity (which in turn improved water fluxes). The membranes poorly rejected monovalent and divalent salts (< 10%), making them resistant to flux decline due to concentration polarization effects. However, the membranes effectively removed carbamazepine, caffeine, sulfamethoxazole, ibuprofen, and naproxen by over 50%. ZnO PES membranes were resistant to organic and protein fouling compared to the neat membrane. ZnO PES ultrafiltration membranes may provide a solution in the reclamation of wastewater.

Keywords: trace organic compounds, pharmaceuticals, membrane fouling, wastewater reclamation

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Authors: Amira Abdelrasoul

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This study aimed to ascertain the controlled permeability of biomimetic cellulose triacetate (CTA) membranes by investigating the electrical oscillatory behavior across impregnated membranes (IM). The biomimetic CTA membranes were infused with a fatty acid to induce electrical oscillatory behavior and, hence, to ensure controlled permeability. In situ synchrotron radiation micro-computed tomography (SR-μCT) at the BioMedical Imaging and Therapy (BMIT) Beamline at the Canadian Light Source (CLS) was used to evaluate the main morphology of IMs compared to neat CTA membranes to ensure fatty acid impregnation inside the pores of the membrane matrices. A monochromatic beam at 20 keV was used for the visualization of the morphology of the membrane. The X-ray radiographs were recorded by means of a beam monitor AA-40 (500 μm LuAG scintillator, Hamamatsu, Japan) coupled with a high-resolution camera, providing a pixel size of 5.5 μm and a field of view (FOV) of 4.4 mm × 2.2 mm. Changes were evident in the phase transition temperatures of the impregnated CTA membrane at the melting temperature of the fatty acid. The pulsations of measured voltages were related to changes in the salt concentration of KCl in the vicinity of the electrode. Amplitudes and frequencies of voltage pulsations were dependent on the temperature and concentration of the KCl solution, which controlled the permeability of the biomimetic membranes. The presented smart biomimetic membrane successfully combined porous polymer support and impregnating liquid not only imitate the main barrier properties of the biological membranes but could be easily modified to achieve some new properties, such as facilitated and active transport, regulation by chemical, physical and pharmaceutical factors. These results open new frontiers for the facilitation and regulation of active transport and permeability through biomimetic smart membranes for a variety of biomedical and drug delivery applications.

Keywords: biomimetic, membrane, synchrotron, permeability, morphology

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Authors: Öznur Özge Özcan, Canan Sercan, Hamza Kulaksız, Mesut Karahan, Korkut Ulucan

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Genetic structure is very important to understand the brain dopamine system which is related to athletic performance. Hopefully, there will be enough studies about athletics performance in the terms of addiction-related genetic markers in the future. In the present study, we intended to investigate the Receptor-2 Gene (DRD2) rs1800497, which is related to brain dopaminergic system. 10 sprinter and 10 endurance athletes were enrolled in the study. Real-Time Polymerase Chain Reaction method was used for genotyping. According to results, A1A1, A1A2 and A2A2 genotypes in athletes were 0 (%0), 3 (%15) and 17 (%85). A1A1 genotype was not found and A2 allele was counted as the dominating allele in our cohort. These findings show that dopaminergic mechanism effects on sport genetic may be explained by the polygenic and multifactorial view.

Keywords: addiction, athletic performance, genotype, sport genetics

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Authors: Mahya Naghipoor

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Purpose: Non-small cell lung cancer (NSCLC) is the most common lung cancer type. Epidermal growth factor receptor (EGFR) mutation is the main reason which causes NSCLC. Computed tomography (CT) is used for diagnosis and prognosis of lung cancers because of low price and little invasion. Semantic analyses of qualitative CT features are based on visual evaluation by radiologist. However, the naked eye ability may not assess all image features. On the other hand, radiomics provides the opportunity of quantitative analyses for CT images features. The aim of this review study was comparing accuracy of semantic and radiomics features in prognosis of EGFR mutation in NSCLC. Methods: For this purpose, the keywords including: non-small cell lung cancer, epidermal growth factor receptor mutation, semantic, radiomics, feature, receiver operating characteristics curve (ROC) and area under curve (AUC) were searched in PubMed and Google Scholar. Totally 29 papers were reviewed and the AUC of ROC analyses for semantic and radiomics features were compared. Results: The results showed that the reported AUC amounts for semantic features (ground glass opacity, shape, margins, lesion density and presence or absence of air bronchogram, emphysema and pleural effusion) were %41-%79. For radiomics features (kurtosis, skewness, entropy, texture, standard deviation (SD) and wavelet) the AUC values were found %50-%86. Conclusions: In conclusion, the accuracy of radiomics analysis is a little higher than semantic in prognosis of EGFR mutation in NSCLC.

Keywords: lung cancer, radiomics, computer tomography, mutation

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Authors: Chyuan Haur Kao, Hsiang Chen, Yu Sheng Tsai, Chen Hao Hung, Yu Shan Lee

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Dielectric electrolyte-insulator-semiconductor sensing membranes-based biosensors have been intensively investigated because of their simple fabrication, low cost, and fast response. However, to enhance their sensing performance, it is worthwhile to explore alternative materials, distinct processes, and novel treatments. An ISFET can be viewed as a variation of MOSFET with the dielectric oxide layer as the sensing membrane. Then, modulation on the work function of the gate caused by electrolytes in various ion concentrations could be used to calculate the ion concentrations. Recently, owing to the advancement of CMOS technology, some high dielectric materials substrates as the sensing membranes of electrolyte-insulator-semiconductor (EIS) structures. The EIS with a stacked-layer of SiO₂ layer between the sensing membrane and the silicon substrate exhibited a high pH sensitivity and good long-term stability. IGZO is a wide-bandgap (~3.15eV) semiconductor of the III-VI semiconductor group with several preferable properties, including good transparency, high electron mobility, wide band gap, and comparable with CMOS technology. IGZO was sputtered by reactive radio frequency (RF) on a p-type silicon wafer with various gas ratios of Ar:O₂ and was treated with rapid thermal annealing in O₂ ambient. The sensing performance, including sensitivity, hysteresis, and drift rate was measured and XRD, XPS, and AFM analyses were also used to study the material properties of the IGZO membrane. Moreover, IGZO was used as a sensing membrane in dielectric EIS bio-sensor structures. In addition to traditional pH sensing capability, detection for concentrations of Na+, K+, urea, glucose, and creatinine was performed. Moreover, post rapid thermal annealing (RTA) treatment was confirmed to improve the material properties and enhance the multi-analyte sensing capability for various ions or chemicals in solutions. In this study, the IGZO sensing membrane with annealing in O₂ ambient exhibited a higher sensitivity, higher linearity, higher H+ selectivity, lower hysteresis voltage and lower drift rate. Results indicate that the IGZO dielectric sensing membrane on the EIS structure is promising for future bio-medical device applications.

Keywords: dielectric sensing membrane, IGZO, hydrogen ion, plasma, rapid thermal annealing

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Lubomir Machuca, Vit Fara

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Ammonium nitrate (AN) is produced by the reaction of ammonia and nitric acid, and a waste condensate is obtained. The condensate contains pure AN in concentration up to 10g/L. The salt content in the condensate is too high to discharge immediately into the river thus it must be treated. This study is concerned with the treatment of condensates from an industrial AN production by combination of electrodialysis (ED) and electrodeionization (EDI). The condensate concentration was in range 1.9–2.5g/L of AN. A pilot ED module with 25 membrane pairs following by a laboratory EDI module with 10 membrane pairs operated continuously during 800 hours. Results confirmed that the combination of ED and EDI is suitable for the condensate treatment.

Keywords: desalination, electrodialysis, electrodeionization, fertilizer industry

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Authors: Sreevalli Bokka

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Various technologies are emerging to capture or reduce carbon intensity from a gas stream, such as industrial effluent air and atmosphere. Of these technologies, filter membranes are emerging as a key player in carbon sequestering. The key advantages of these membranes are their high surface area and porosity. Fabricating a filter membrane that has high selectivity for carbon sequestration is challenging as material properties and processing parameters affect the membrane properties. In this study, the growth of the filter membranes and the critical material properties that impact carbon sequestration are presented.

Keywords: membranes, filtration, separations, polymers, carbon capture

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Authors: Adesola O. Orimoloye, Edward Gobina

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Flue gas is the most prevalent source of carbon dioxide off-gas from numerous processes globally. Among the lion's share of this flue gas is the ever-present electric power plant, primarily fuelled by coal, and then secondly, natural gas. The carbon dioxide found in coal fired power plant off gas is among the dirtiest forms of carbon dioxide, even with many of the improvements in the plants; still this will yield sulphur and nitrogen compounds; among other rather nasty compounds and elements; all let to the atmosphere. This presentation will focus on the characterization of carbon dioxide-rich flue gas sources with a view of eventual conversion to chemicals and fuels using novel membrane reactors.

Keywords: flue gas, carbon dioxide, membrane, catalyst, syngas

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Authors: Swetha Priya Darshini Thammadi, Sateesh Kumar Pisini, Sanjay Kumar Shukla

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Source apportionment using Dispersion model depends primarily on the quality of Emission Inventory. In the present study, a CMB receptor model has been used to identify the sources of PM_2.5, while the AERMOD dispersion model has been used to account for missing sources of PM_2.5 in the Emission Inventory. A statistical approach has been developed to quantify the missing sources not considered in the Emission Inventory. The inventory of each grid was improved by adjusting emissions based on road lengths and deficit in measured and modelled concentrations. The results showed that in CMB analyses, fugitive sources - soil and road dust - contribute significantly to ambient PM_2.5 pollution. As a result, AERMOD significantly underestimated the ambient air concentration at most locations. The revised Emission Inventory showed a significant improvement in AERMOD performance which is evident through statistical tests.

Keywords: CMB, GIS, AERMOD, PM₂.₅, fugitive, emission inventory

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Authors: M. F. R. Zuthi, H. H. Ngo, W. S. Guo, S. S. Chen, N. C. Nguyen, L. J. Deng, T. D. C Tran

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Sustaining a desired rate of oxygen transfer for microbial activity is a matter of major concern for Biological Wastewater Treatment (MBR). The study reported in the paper was aimed at assessing the effects of microbial products on the Specific Oxygen Uptake Rate (SOUR) in a Conventional Membrane Bioreactor (CMBR) and that in a Sponge Submerged MBR (SSMBR). The production and progressive accumulation of Soluble Microbial Products (SMP) and Bound-Extracellular Polymeric Substances (BEPS) were found affecting the SOUR of the microorganisms which varied at different stages of operation of the MBR systems depending on the variable concentrations of the SMP/bEPS. The effect of bEPS on the SOUR was stronger in the SSMBR compared to that of the SMP, while relative high concentrations of SMP had adverse effects on the SOUR of the CMBR system. Of the different mathematical correlations analyzed in the study, logarithmic mathematical correlations could be established between SOUR and bEPS in SSMBR, and similar correlations could also be found between SOUR and SMP concentrations in the CMBR.

Keywords: microbial products, microbial activity, specific oxygen uptake rate, membrane bioreactor

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Authors: Eric Chappel, Dimitry Dumont-Fillon, Hugo Musard, Harald van Lintel

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A microfluidic radial diffuser typically comprises a hole in a membrane, a small gap and pillar centred with the hole. The fluid is forced to flow radially in this gap between the membrane and the pillar. Such diffusers are notably used to form flow control valves, wherein several holes are machined into a flexible membrane progressively deflecting against pillars as the pressure increases. The fluidic modelling of such diffuser is made difficult by the presence of a transition region between the hole and the diffuser itself. An experimental investigation has been conducted using SOI wafers to form membranes with only one centred hole and Pyrex wafers for the substrate and pillars, both wafers being anodically bonded after alignment. A simple fluidic model accounting for the specific geometry of the diffuser is proposed and compared to experimental results. A good match is obtained, for Reynolds number in the range 0.5 to 35 using the analytical formula of a radial diffuser in the laminar regime with an effective inner radius that is 40% smaller than the real radius, in order to simulate correctly the flow constriction at the entrance of the diffuser.

Keywords: radial diffuser, flow control valve, numerical modelling, drug delivery

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Authors: Qing Cao, Fei Wang, Yu-Qiang Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen

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Aims: TNF Receptor-Associated Factor 6 (TRAF6) acts as a multifunctional regulator of the Transforming Growth Factor (TGF)-β signaling pathway, and mediates Smad-independent JNK and p38 activation via TGF-β. This study was performed to test the hypothesis that TGF-β/TRAF6 is essential for angiotensin-II (Ang II)-induced differentiation of rat c-kit+ Cardiac Stem Cells (CSCs). Methods and Results: c-kit+ CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) or the small interfering RNA (siRNA)-mediated knockdown of TRAF6 were used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR deleted siRNA insensitive construct was conducted to rule out the off target effects of the siRNA. TRAF6 dominant negative (TRAF6DN) vector was constructed and used to infect c-kit+ CSCs, and western blotting was used to assess the expression of TRAF6, JNK, p38, cardiac-specific proteins, and Wnt signaling proteins. Physical interactions between TRAF6 and TGFβ receptors were studied by coimmunoprecipitation. Cardiac differentiation was suppressed in the absence of TRAF6. Forced expression of TRAF6 enhanced the expression of TGF-β-activated kinase1 (TAK1), and inhibited Wnt signaling. Furthermore, TRAF6 increased the expression of cardiac-specific proteins (cTnT and Cx-43) but inhibited the expression of Wnt3a. Conclusions: Our data suggest that TRAF6 plays an important role in Ang II induced differentiation of c-kit+ CSCs via the non-canonical signaling pathway.

Keywords: cardiac stem cells, differentiation, TGF-β, TRAF6, ubiquitination, Wnt

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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Authors: Vinod Kumar

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Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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Authors: Hamidreza Sharifan, Audra Morse

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Accurate assessments of contaminant concentrations based on traditional grab sampling methods are not always possible. Passive samplers offer an attractive alternative to traditional sampling methods that overcomes these limitations. The POCIS approach has been used as a screening tool for determining the presence/absence, possible sources and relative amounts of organic compounds at field sites. The objective for the present research is on mass transfer of five water contaminants (atrazine, caffeine, bentazon, ibuprofen, atenolol) through the Water Boundary Layer (WBL) and membrane. More specific objectives followed by establishing a relationship between the sampling rate and water solubility of the compounds, as well as comparing the molecular weight of the compounds and concentration of the compounds at the time of equilibrium. To determine whether water boundary layer effects transport rate through the membrane is another main objective in this paper. After GC mass analysis of compounds, regarding the WBL effect in this experiment, Sherwood number for the experimental tank developed. A close relationship between feed concentration of compound and sampling rate has been observed.

Keywords: passive sampler, water contaminants, PES-transfer rate, contaminant concentrations

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Authors: Jingjing Huang, Nengwei Li, Guanghua Wei, Jiabin You, Chao Wang, Junliang Zhang

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In this work, molecular dynamics (MD) simulation is applied to analyze the mass transport process in the cathode of proton exchange membrane fuel cell (PEMFC), of which all types of molecules situated in the cathode is considered. a reasonable and effective MD simulation process is provided, and models were built and compared using both Materials Studio and LAMMPS. The mass transport is one of the key issues in the study of proton exchange membrane fuel cells (PEMFCs). In this report, molecular dynamics (MD) simulation is applied to analyze the influence of Nafion ionomer distribution and Pt nano-particle size on mass transport process in the cathode. It is indicated by the diffusion coefficients calculation that a larger quantity of Nafion, as well as a higher equivalent weight (EW) value, will hinder the transport of oxygen. In addition, medium-sized Pt nano-particles (1.5~2nm) are more advantageous in terms of proton transport compared with other particle sizes (0.94~2.55nm) when the center-to-center distance between two Pt nano-particles is around 5 nm. Then mass transport channels are found to be formed between the hydrophobic backbone and the hydrophilic side chains of Nafion ionomer according to the radial distribution function (RDF) curves. And the morphology of these channels affected by the Pt size is believed to influence the transport of hydronium ions and, consequently the performance of PEMFC.

Keywords: cathode catalytic layer, mass transport, molecular dynamics, proton exchange membrane fuel cell

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Chi-Chang Lin, Jiun-Yan Chiu

Abstract:

Periodontal disease, oral cancer relating trauma is the prominent factor devastating bone tissue that is crucial to reestablishing in clinical. As we know, common symptom, osteoporosis, and infection limiting the ability of the bone tissue to recover cause difficulty before implantation therapy. Regeneration of bone tissue is the fundamental therapy before surgical processes. To promote the growth of bone tissue, many commercial products still have sophisticated problems that need to overcome. Regrettably, there is no available material which is apparently preferable for releasing and controlling of loading dosage, or mitigating inflammation. In our study, a hydrogel-based composite membrane has been prepared by using Gellan gum (GG), gamma-polyglutamic acid (γ-PGA) and glycerol with simple sol-gel method. GG is a natural material that is massively adopted in cartilage. Unfortunately, the strength of pure GG film is a manifest weakness especially under simulating body fluidic conditions. We utilize another biocompatible material, γ-PGA as cross-linker which can form tri-dimension structure that enhancing the strength. Our result indicated the strength of pure GG membrane can be obviously improved by cross-linked with γ-PGA (0.5, 0.6, 0.7, 0.8, 0.9, 1.0 w/v%). Besides, blending with glycerol (0, 1.0, 2.0, 3.0 w/v%) can significantly improve membrane toughness that corresponds to practical use. The innovative composited hydrogel made of GG, γ-PGA, and glycerol is attested with neat results including elongation and biocompatibility that take the advantage of extension covering major trauma. Recommendations are made for treatment to build up the foundation of bone tissue that would help patients to escape from the suffering and shorten the amount of time in recovery.

Keywords: bone tissue, gellan gum, regeneration, toughness

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Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

Abstract:

Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

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Authors: I. Nur Hilwani, R. Nasibah, S. Nurdiana, M. J. Norashirene

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Impaired fertility may be the result of indirect consumption of anti-fertility agents through food. Monosodium glutamate (MSG) has been widely used as food additive, flavour enhancer and included in vaccines. This study focuses in determining the gonadotoxic and cytotoxic effect of MSG on selected sperm parameters such as sperm viability, sperm membrane integrity and testes cytoarchitecture of male mice via histological examination to determine its effect on spermatogenesis. Twenty-four Mus musculus were randomly divided into 4 groups and given intraperitoneal injections (IP) daily for 14 days of different MSG concentrations at 250, 500 and 1000mg/kg MSG to body weight to induce obesity. Saline was given to control group. Mice were sacrificed and analysis revealed abnormalities in values for sperm parameters and damages to testes cytoarchitecture of male mice. The results recorded decreased viability (p<0.05) and integrity of sperm membrane (p>0.05) with degenerative structures in seminiferous tubule of testes. The results indicated various implications of MSG on male mice reproductive system which has consequences in fertility potential.

Keywords: sperm parameter, testes histology, sperm viability, sperm membrane integrity

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Authors: Dipanshu Sur, Ratnabali Chakravorty

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Background: Polycystic ovary syndrome (PCOS) is the most common metabolic abnormality such as changes in lipid profile, diabetes, hypertension and metabolic syndrome occurring in young women of reproductive age. Low vitamin D levels were found to be associated with the development of obesity and insulin resistance in women with PCOS. Variants on vitamin D receptor (VDR) gene have also been related to metabolic comorbidities in general population. Aim: The aim of this case-control study was to investigate whether the VDR gene polymorphisms are associated with susceptibility to PCOS. Methods: Women with PCOS and a control group, all aged 16-40 years, were enrolled. Genotyping of VDR Fok-I (rs2228570), VDR Apa-I (rs7975232) as well as GC (rs2282679), DHCR7 (rs12785878) SNPs between groups were determined by using direct sequencing. Serum 25-hydroxyvitamin D [25(OH)] levels were measured by ELISA. Results: Mean serum 25(OH)D in the PCOS and control samples were 19.08±7 and 23.27±6.03 (p=0.048) which were significantly lower in PCOS patients compared with controls. CC genotype of the VDR Apa-I SNP was same frequent in PCOS (25.6%) and controls (25.6%) (OR: 0.9995; 95%CI: 0.528 to 1.8921; p= 0.9987). The CC genotype was also significantly associated with both lower E2 (p=0.031) and Androstenedione levels (p=0.062). We observed a significant association of GC polymorphism with 25(OH)D levels. PCOS women carrying the GG genotype (in GC genes) had significantly higher risk for vitamin D deficiency than women carrying the TT genotype. Conclusions: In conclusion, data from this study indicate that vitamin D levels are lower, and vitamin D deficiency more frequent, in PCOS than in controls. The present findings suggest that the Apa-I, Fok-I polymorphism of the VDR gene is associated with PCOS and seems to modulate ovarian steroid secretion. Further studies are needed to better clarify the biological mechanisms by which the polymorphism influences PCOS risk.

Keywords: vitamin D receptor, polymorphism, vitamin D, polycystic ovary syndrome

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Authors: P. Tirgarbahnamiri, S. Mahravani, N. Haddadpour, F. Yaghmaie, F. Barazandeh

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In this study, silver nanoparticle-Polydimethylsiloxane membrane (SNP-PDMS) was prepared with an in-situ reduction method using AgNO3 in poly (dimethylsiloxane) hardener. Optical and mechanical properties as well as functionality of these membranes were determined employing, UV-Vis spectrophotometry, FTIR, strain-stress test and liquid/liquid filtration measurements. Silver nanoparticles are known to selectively absorb Olefins and may be used for separation of Alkanes from olefins. Yellow color of silver nanocomposites and transparency of blank polymer were observed employing optical microscope. λmax in 415-420 nm regions in UV-Vis spectrophotometry are related to silver nanoparticles absorbance. Based on stress-strain test results, tensile strength of silver nanoparticle PDMS (SNP-PDMS) membranes is higher than PDMS films of comparable size and thickness. Moreover, permeability of SNP-PDMS membranes were characterized using similar olefin/paraffin pair using a simple bench scale separation set- up. The silver -PDMS membranes retain their color and UV-vis characteristics for extended periods of time exceeding several months.

Keywords: nanocomposite membrane, gas separation, facilitated transport, silver nanocomposite, PDMS, in-situ reduction

Procedia PDF Downloads 308

Authors: Aimad Oulebsir, Toufik Chaabane, Sivasankar Venkatramann, Andre Darchen, Rachida Maachi

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The objective of this study is to propose a model for the prediction of the mechanism transfer of the trivalent ions through a nanofiltration membrane (NF) by introduction of the polarization concentration phenomenon and to study its influence on the retention of salts. This model is the combination of the Nernst-Planck equation and the equations of the film theory. This model is characterized by two transfer parameters: Reflection coefficient s and solute permeability Ps which are estimated numerically. The thickness of the boundary layer, δ, solute concentration at the membrane surface, Cm, and concentration profile in the polarization layer have also been estimated. The mathematical formulation suggested was established. The retentions of trivalent salts are estimated and compared with the experimental results. A comparison between the results with and without phenomena of polarization of concentration is made and the thickness of boundary layer alimentation side was given. Experimental and calculated results are shown to be in good agreement. The model is then success fully extended to experimental data reported in the literature.

Keywords: nanofiltration, concentration polarisation, chromium salts, mass transfer

Procedia PDF Downloads 263

Authors: Wen-Ting Wang, Wei-An Tsai, Rong-Hong Hsieh

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Long term taking high fat diet can lead to over production of energy, result in accumulation of body fat, dyslipidemia and increased lipid metabolism in the body. Over metabolism of lipid results in excessive reactive oxygen species and oxidative stress, may also cause mitochondrial dysfunction and cell death. Krill oil, fish oil and linseed oil are good sources of n-3 polyunsaturated fatty acids (PUFA). The present study investigated the effect of high fat diet and various oil rich of n-3 fatty acids on mitochondrial function and cell membrane composition. Six-weeks old male Spraque-Dawley rats were randomly divided into 8 groups including: control group, high fat diet group, low dosage and high dosage krill oil group, low dosage and high dosage fish oil group, and low dosage and high dosage linseed oil group. After 12 weeks of experimental period, the low dosage krill oil, fish oil group and linseed oil group with different dosage prevented mitochondrial dysfunction caused by high fat diet. The supplementation of different oils increased plasma, erythrocyte and mitochondrial n-3/n-6 ratio and further increased the proportion of PUFA in erythrocyte and mitochondrial membrane. It also decreased serum triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) concentration. However, there was no significant change in serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), biomarker of liver function, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and plasma malonadialdehyde (MDA) concentration when compared with high fat diet group. The supplementation of different sources of n-3 PUFA can maintain mitochondrial function and modulate cell membrane fatty acid composition in high fat diet conditions, and there is a positive relationship between mitochondrial function and mitochondrial membrane composition.

Keywords: fish oil, linseed oil, mitochondria, n-3 PUFA

Procedia PDF Downloads 390

Authors: Mohaya Farzin, Shahin Hassanpour, Morteza Zendehdel, Bita Vazir, Ahmad Asghari

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Aim: There are several differences between birds and mammals in terms of food intake regulation. Therefore, this study aimed to investigate the effects of the intracerebroventricular (ICV) injection of spexin and its interaction with nitric oxide, serotonin, and corticotropin receptors on central food intake regulation in broiler chickens. Materials and Methods: In experiment 1, chickens received ICV injection of saline, PCPA (p-chlorophenyl alanine,1.25 µg), spexin, and PCPA+spexin. In experiments 2-7, 8-OH-DPAT (5-HT1A agonist, 15.25 nmol), SB-242084 (5-HT2C receptor antagonist, 1.5µg), L-arginine (Precursor of nitric oxide, 200 nmol), L-NAME (nitric oxide synthetase inhibitor, 100 nmol), Astressin-B (CRF1/CRF2 receptor antagonist, 30 µg) and Astressin2-B (CRF2 receptor antagonist, 30 µg) were injected to chickens instead of the PCPA. Then, food intake was measured until 120 minutes after the injection. Results: Spexin significantly decreased food consumption (P<0.05). Concomitant injection of SB-242084+spexin attenuated spexin-induced hypophagia (P<0.05). Co-injection of L-arginine+spexin enhanced spexin-induced hypophagia, and this effect was reversed by L-NAME (P<0.05). Also, concomitant injection of Astressin-B + spexin or Astressin2-B + spexin enhanced spexin-induced hypophagia (P<0.05). Conclusions: Based on these observations, spexin-induced hypophagia may be mediated by nitric oxide and 5-HT2C, CRF1, and CRF2 receptors in neonatal broiler chickens.

Keywords: spexin, serotonin, corticotropin, nitric oxide, food intake, chicken

Procedia PDF Downloads 54

Authors: Elizaveta Korzhova, Sebastien Deon, Patrick Fievet, Dmitry Lopatin, Oleg Baranov

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Filtration with nanoporous ultrafiltration membranes is an attractive option to remove ionic pollutants from contaminated effluents. Unfortunately, commercial membranes are not necessarily suitable for specific applications, and their modification by polymer deposition is a fruitful way to adapt their performances accordingly. Many methods are usually used for surface modification, but a novel technique based on electrospray is proposed here. Various quantities of polymers were deposited on a commercial membrane, and the impact of the deposit is investigated on filtration performances and discussed in terms of charge and hydrophobicity. The electrospray deposition is a technique which has not been used for membrane modification up to now. It consists of spraying small drops of polymer solution under a high voltage between the needle containing the solution and the metallic support on which membrane is stuck. The advantage of this process lies in the small quantities of polymer that can be coated on the membrane surface compared with immersion technique. In this study, various quantities (from 2 to 40 μL/cm²) of solutions containing two charged polymers (13 mmol/L of monomer unit), namely polyethyleneimine (PEI) and polystyrene sulfonate (PSS), were sprayed on a negatively charged polyethersulfone membrane (PLEIADE, Orelis Environment). The efficacy of the polymer deposition was then investigated by estimating ion rejection, permeation flux, zeta-potential and contact angle before and after the polymer deposition. Firstly, contact angle (θ) measurements show that the surface hydrophilicity is notably improved by coating both PEI and PSS. Moreover, it was highlighted that the contact angle decreases monotonously with the amount of sprayed solution. Additionally, hydrophilicity enhancement was proved to be better with PSS (from 62 to 35°) than PEI (from 62 to 53°). Values of zeta-potential (ζ were estimated by measuring the streaming current generated by a pressure difference on both sides of a channel made by clamping two membranes. The ζ-values demonstrate that the deposits of PSS (negative at pH=5.5) allow an increase of the negative membrane charge, whereas the deposits of PEI (positive) lead to a positive surface charge. Zeta-potentials measurements also emphasize that the sprayed quantity has little impact on the membrane charge, except for very low quantities (2 μL/m²). The cross-flow filtration of salt solutions containing mono and divalent ions demonstrate that polymer deposition allows a strong enhancement of ion rejection. For instance, it is shown that rejection of a salt containing a divalent cation can be increased from 1 to 20 % and even to 35% by deposing 2 and 4 μL/cm² of PEI solution, respectively. This observation is coherent with the reversal of the membrane charge induced by PEI deposition. Similarly, the increase of negative charge induced by PSS deposition leads to an increase of NaCl rejection from 5 to 45 % due to electrostatic repulsion of the Cl- ion by the negative surface charge. Finally, a notable fall in the permeation flux due to the polymer layer coated at the surface was observed and the best polymer concentration in the sprayed solution remains to be determined to optimize performances.

Keywords: ultrafiltration, electrospray deposition, ion rejection, permeation flux, zeta-potential, hydrophobicity

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

Abstract:

Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

Procedia PDF Downloads 147