Search results for: mitochondrial membrane

Authors: Shah Abid

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Leishmaniasis is a collection of zoonotic infections that affect the viscera, skin, and mucous membrane and are spread by several species of female sandflies in the subfamily phlebotominae. The study's goal was to assess the prevalence of Cutaneous Leishmaniasis in District Kurram using descriptive and cross-sectional methods. From December 2022 to May 2023, the study was carried out at Tehsil Head Quarter (THQ) Hospital, Sadda, District Kurram in the Dermatology Department. The disease was identified using a laboratory method based on clinical manifestations of leishmaniasis. A clean slide's surface was applied to the scraped-off portion of the lesions and rubbed over the blood to make a smear on the slide. The slides were methanol-fixed, stained with traditional Giemsa, and meticulously examined at high magnification to search for LD bodies. The necessary information, such as residence area, lesion kind and location, age, sex, and the total number of lesions, was meticulously acquired. During the time of the investigation, 393 instances of cutaneous leishmaniasis were observed. 1 year to 70 years old was the age range (mean age: 35.45). The age group that was most severely impacted, 16 years and older, had 23 (11.67%) children with this condition. Male to female ratio was 9.7:10. Most of the cases (n=52, 26.29%), were reported in the month of May. Majority of the patients 102 (51.77%) had lesion on face. 42 (16.73) patients had multiple lesions on their body. Face was the most common site followed by lower limbs 93 (37.05). Weekly intralesional injections of sodium stibogluconate (glucantime) were administered to all patients. Without any noticeable adverse effects, all patients had positive responses to the treatment. The condition affects adults more commonly than children, according to analysis of the combined results, and it is more common in women than in men.

Keywords: District Kurram, cutaneous leishmaniasis, zoonosis, glucantime

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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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Authors: Yahia Massinissa, Benhouda Afaf, Benbia Souhila, Meddour Noura, Takellalet Karima, Zeroual Amina

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Introduction: chenopodiaceae family species are known for their important biological activity, in which Atriplex halimus belongs . However, the inflammatory effect of this plant leaves has not been studied. This work aimed at assessing the anti- inflammatory and hemostatic activities of the methanolic extract AHMeOH of Atriplex halimus’s leaves. Methods: The extract was obtained using sonication of leaves powder in 80 % methanol. The analysis of phenolic compounds was carried out using thin-layer chromatography (TLC).The anti-inflammatory activity was determined by studying the plasmical membrane stabilization and albumin denaturation inhibition, the hemostatic activity was evaluated by measuring the plasma in the blood. Results: Quantitative determination of total flavonoids reveals that AHMeOH is rich in flavonoids (16 ± 0.88 μg Q / mg extract) and polyphenols (20 ± 0.20 μg AG / mg extract). about anti-inflammatory activity, the tests show that AHMeOH has a significant effect (P≤0.05) of inhibiting hypotonic-induced hemolysis with concentrations (100 and 200 μg / ml) with 77.55 and 90% respectively, and heat-induced hemolysis with percentages 81.75% and 87.44% respectively with significant difference (P ≤0.05). The obtained results with this plant reveal that the inhibition of denaturation of albumin is dose dependent. The concentration of 400 μg / ml gives denaturation inhibition of 81.00 ± 17.70% and the concentration 600 μg / ml gives an effect of 82.95 ± 17.40%. Regarding the haemostatic activity our extract with the doses 10 mg / ml, 20 mg / ml and 30 mg / ml confer a decrease of the plasma recalcification time in the tube, these concentrations could prolong the time of coagulation significantly compared to the control (P≤0.001). This result is an interesting indication in favor of haemostatic activity of AHMeOH. Conclusion: Atriplex Halimus has a strong anti-inflammatory activity and constitutes a potential source for the development of new treatments.

Keywords: albumin, atriplex halimus, hemostatic activity, methanolic extract

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Authors: Ridhish Kumar, Sudeep Nadukkandy, Anirban Roy

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The development of reverse osmosis happened in 1960. Along the years this technique has been widely accepted all over the world for varied applications ranging from seawater desalination to municipal water treatment. Forward osmosis (FO) is one of the foremost technologies for low energy consuming solutions for water purification. In this study, we have carried out a detailed analysis on selection, design, and pricing for a prototype of potable water system for purifying water in emergency situations. The portable and light purification system is envisaged to be driven by FO. This pouch will help to serve as an emergency water filtration device. The current effort employs a model to understand the interplay of permeability and area on the rate of purification of water from any impure source/brackish water. The draw solution for the FO pouch is considered to be a combination of salt and sugar such that dilution of the same would result in an oral rehydration solution (ORS) which is a boon for dehydrated patients. However, the effort takes an extra step to actually estimate the cost and pricing of designing such a prototype. While the mathematical model yields the best membrane (compositions are taken from literature) combination in terms of permeability and area, the pricing takes into account the feasibility of such a solution to be made available as a retail item. The product is envisaged to be a market competitor for packaged drinking water and ORS combination (costing around $0.5 combined) and thus, to be feasible has to be priced around the same range with greater margins in order to have a better distribution. Thus a proper business plan and production of the same has been formulated in order to be a feasible solution for unprecedented calamities and emergency situations.

Keywords: forward osmosis, water treatment, oral rehydration solution, prototype

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Authors: Mehmet Bulent Topkaya, Mustafa Yildirim

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Wastewater treatment systems are designed and used to minimize adverse impacts of the wastewater on the environment before discharging. Various treatment options for wastewater treatment have been developed, and each of them has different performance characteristics and environmental impacts (e.g. material and land usage, energy consumption, greenhouse gas emission, water and soil emission) during construction, operation or maintenance phases. Assessing the environmental impacts during these phases are essential for the overall evaluation of the treatment systems. In this study, wastewater treatment options, such as vegetated land treatment, constructed wetland, rotating biological contactor, conventional activated sludge treatment, membrane bioreactor, extended aeration and stabilization pond are evaluated. The comparison of the environmental impacts is conducted under the assumption that the effluents will be discharged to sensitive and less sensitive areas respectively. The environmental impacts of each alternative are evaluated by life cycle assessment (LCA) approach. For this purpose, data related to energy usage, land requirement, raw material consumption, and released emissions from the life phases were collected with inventory studies based on field studies and literature. The environmental impacts were assessed by using SimaPro 7.1 LCA software. As the scale of the LCA results is global, an MS-Excel based decision support tool that includes the LCA result is developed in order to meet also the local demands. Using this tool, it is possible to assign weight factors on the LCA results according to local conditions by using Analytical Hierarchy Process and finally the most environmentally appropriate treatment option can be selected.

Keywords: analytical hierarchy process, decision support system, life cycle assessment, wastewater treatment

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Authors: Gabriela Borilova, Monika Petrakova, Petr Kralik

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Nowadays, European producers are increasingly interested in the production of halal meat products. Halal meat has been increasingly appearing in the EU's market network and meat products from European producers are being exported to Islamic countries. Halal criteria are mainly related to the origin of muscle used in production, and also to the way products are obtained and processed. Although the EU has legislatively addressed the question of food authenticity, the circumstances of previous years when products with undeclared horse or poultry meat content appeared on EU markets raised the question of the effectiveness of control mechanisms. Replacement of expensive or not-available types of meat for low-priced meat has been on a global scale for a long time. Likewise, halal products may be contaminated (falsified) by pork or food components obtained from pigs. These components include collagen, offal, pork fat, mechanically separated pork, emulsifier, blood, dried blood, dried blood plasma, gelatin, and others. These substances can influence sensory properties of the meat products - color, aroma, flavor, consistency and texture or they are added for preservation and stabilization. Food manufacturers sometimes access these substances mainly due to their dense availability and low prices. However, the use of these substances is not always declared on the product packaging. Verification of the presence of declared ingredients, including the detection of undeclared ingredients, are among the basic control procedures for determining the authenticity of food. Molecular biology methods, based on DNA analysis, offer rapid and sensitive testing. The PCR method and its modification can be successfully used to identify animal species in single- and multi-ingredient raw and processed foods and qPCR is the first choice for food analysis. Like all PCR-based methods, it is simple to implement and its greatest advantage is the absence of post-PCR visualization by electrophoresis. qPCR allows detection of trace amounts of nucleic acids, and by comparing an unknown sample with a calibration curve, it can also provide information on the absolute quantity of individual components in the sample. Our study addresses a problem that is related to the fact that the molecular biological approach of most of the work associated with the identification and quantification of animal species is based on the construction of specific primers amplifying the selected section of the mitochondrial genome. In addition, the sections amplified in conventional PCR are relatively long (hundreds of bp) and unsuitable for use in qPCR, because in DNA fragmentation, amplification of long target sequences is quite limited. Our study focuses on finding a suitable genomic DNA target and optimizing qPCR to reduce variability and distortion of results, which is necessary for the correct interpretation of quantification results. In halal products, the impact of falsification of meat products by the addition of components derived from pigs is all the greater that it is not just about the economic aspect but above all about the religious and social aspect. This work was supported by the Ministry of Agriculture of the Czech Republic (QJ1530107).

Keywords: food fraud, halal food, pork, qPCR

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Authors: M. Kashfi, K. Jahani

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Sound attenuation in absorptive silencers has been analyzed in this paper. The structure of such devices is as follows. When the rigid duct of an expansion chamber has been lined by a packed absorptive material under a perforated membrane, incident sound waves will be dissipated by the absorptive liners. This kind of silencer, usually are applicable for medium to high frequency ranges. Several conditions for different absorptive materials, variety in their thicknesses, and different shapes of the expansion chambers have been studied in this paper. Also, graphs of sound attenuation have been compared between empty expansion chamber and duct of silencer with applying liner. Plane waves have been assumed in inlet and outlet regions of the silencer. Presented results that have been achieved by applying finite element method (FEM), have shown the dependence of the sound attenuation spectrum to flow resistivity and the thicknesses of the absorptive materials, and geometries of the cross section (configuration of the silencer). As flow resistivity and thickness of absorptive materials increase, sound attenuation improves. In this paper, diagrams of the transmission loss (TL) for absorptive silencers in five different cross sections (rectangle, circle, ellipse, square, and rounded rectangle as the main geometry) have been presented. Also, TL graphs for silencers using different absorptive material (glass wool, wood fiber, and kind of spongy materials) as liner with three different thicknesses of 5 mm, 15 mm, and 30 mm for glass wool liner have been exhibited. At first, the effect of substances of the absorptive materials with the specific flow resistivity and densities on the TL spectrum, then the effect of the thicknesses of the glass wool, and at last the efficacy of the shape of the cross section of the silencer have been investigated.

Keywords: transmission loss, absorptive material, flow resistivity, thickness, frequency

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Authors: J. P. Chica Cano, G. Cabot, S. de Persis, F. Foucher

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Among all possibilities to combat global warming, CO₂ capture and sequestration (CCS) is presented as a great alternative to reduce greenhouse gas (GHG) emission. Several strategies for CCS from industrial and power plants are being considered. The concept of combined oxy-fuel combustion has been the most alternative solution. Nevertheless, due to the high cost of pure O₂ production, additional ways recently emerged. In this paper, an innovative combustion process for a gas turbine cycle was studied: it was composed of methane combustion with oxygen enhanced air (OEA), exhaust gas recirculation (EGR) and H₂O issuing from STIG (Steam Injection Gas Turbine), and the CO₂ capture was realized by membrane separator. The effect on this combustion process was emphasized, and it was shown that a study of the influence of H₂O dilution on the combustion parameters by experimental and numerical approaches had to be carried out. As a consequence, the laminar burning velocities measurements were performed in a stainless steel spherical combustion from atmospheric pressure to high pressure (up to 0.5 MPa), at 473 K for an equivalence ratio at 1. These experimental results were satisfactorily compared with Chemical Workbench v.4.1 package in conjunction with GRIMech 3.0 reaction mechanism. The good correlations so obtained between experimental and calculated flame speed velocities showed the validity of the GRIMech 3.0 mechanism in this domain of combustion: high H₂O dilution, low N₂, medium pressure. Finally, good estimations of flame speed and pollutant emissions were determined in other conditions compatible with real gas turbine. In particular, mixtures (composed of CH₄/O₂/N₂/H₂O/ or CO₂) leading to the same adiabatic temperature were investigated. Influences of oxygen enrichment and H₂O dilution (compared to CO₂) were disused.

Keywords: CO₂ capture, oxygen enrichment, water dilution, laminar burning velocity, pollutants emissions

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Chen Jun-Hong, He Pu, Tao Wen-Quan

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Proton exchange membrane fuel cell (PEMFC) is the most promising future energy source owing to its low operating temperature, high energy efficiency, high power density, and environmental friendliness. In this paper, a comprehensive PEMFC system control-oriented model is developed in the Matlab/Simulink environment, which includes the hydrogen supply subsystem, air supply subsystem, and thermal management subsystem. Besides, Improved Artificial Bee Colony (IABC) is used in the parameter identification of PEMFC semi-empirical equations, making the maximum relative error between simulation data and the experimental data less than 0.4%. Operation temperature is essential for PEMFC, both high and low temperatures are disadvantageous. In the thermal management subsystem, water pump and fan are both controlled with the PID controller to maintain the appreciate operation temperature of PEMFC for the requirements of safe and efficient operation. To improve the control effect further, fuzzy control is introduced to optimize the PID controller of the pump, and the Radial Basis Function (RBF) neural network is introduced to optimize the PID controller of the fan. The results demonstrate that Fuzzy-PID and RBF-PID can achieve a better control effect with 22.66% decrease in Integral Absolute Error Criterion (IAE) of T_st (Temperature of PEMFC) and 77.56% decrease in IAE of T_in (Temperature of inlet cooling water) compared with traditional PID. In the end, a novel thermal management structure is proposed, which uses the cooling air passing through the main radiator to continue cooling the secondary radiator. In this thermal management structure, the parasitic power dissipation can be reduced by 69.94%, and the control effect can be improved with a 52.88% decrease in IAE of T_in under the same controller.

Keywords: PEMFC system, parameter identification, temperature control, Fuzzy-PID, RBF-PID, parasitic power

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Authors: Meryem Zarri, Mohame Tahiri, Fouad Amraoui

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In the context of water resources shortage that Morocco is experiencing in recent years, the mobilization of non-conventional resources becomes a necessity. The reuse of treated water and the bioconversion of biological sewage sludge into value-added products is considered an environmentally friendly and economical approach to the management of this significant resource which represent at least 80 % of consumed fresh wate In this work, we compare the quality of treated water and sewage sludge from wastewater treatment plants in the peri-urban Casablanca by analyzing different physicochemical and bacteriological parameters. The choice was made for three wastewater plants installed in different regions and monitored either by LYDEC and Commune of Had Soualem and use different technologies. Recycling of treated water in agriculture and watering of green spaces is dependent on the compliance of the parameters with international standards (WHO, FAO, …etc.) The preliminary tests of the samples taken during the second half of the year 2021 showed that the advanced technologies put in place at the level of the Mediouna and the airport zone stations (membrane reactor and activated sludge, respectively) give water to the output of the stations more respectful of the standards required in terms of physicochemical parameters (pH, Conductivity, Tubidity, COD, BOD5, TNK, and TPK) and bacteriological (fecal germs, Escherichia Coli, streptococci, Helminthes eggs). The parameters relating to the Had Soualem natural lagoon station are generally at the tolerance’s threshold. The results of analyzes relating to the residual sludge collected at the end of the cycle are, on the whole satisfactory despite a fluctuating variability of the bacteriological parameters.

Keywords: urban wastewater treatment plants, purified wastewater, sewage sludge, physicochemical parameters, bacteriological parameters, peri-urban area of ​​casablanca, morocco

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: Pooja Kumbhare

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Water is an important resource for the survival of life. The inadequate availability of surface water makes people depend on ground water for fulfilling their needs. However, ground water is generally too hard to satisfy the requirements for domestic as well as industrial applications. Removal of hardness involves various techniques such as lime soda process, ion exchange, reverse osmosis, nano-filtration, distillation, and, evaporation, etc. These techniques have individual problems such as high annual operating cost, sediment formation on membrane, sludge disposal problem, etc. Electrocoagulation (EC) is being explored as modern and cost-effective technology to cope up with the growing demand of high water quality at the consumer end. In general, earlier studies on electrocoagulation for hardness removal are found to deploy batch processes. As batch processes are always inappropriate to deal with large volume of water to be treated, it is essential to develop continuous flow EC process. So, in the present study, an attempt is made to investigate continuous flow EC process for decreasing excessive hardness of bore-well water. The experimental study has been conducted using 12 aluminum electrodes (25cm*10cm, 1cm thick) provided in EC reactor with volume of 8 L. Bore well water sample, collected from a local bore-well (i.e. at – Vishrambag, Sangli; Maharashtra) having average initial hardness of 680 mg/l (Range: 650 – 700 mg/l), was used for the study. Continuous flow electrocoagulation experiments were carried out by varying operating parameters specifically reaction time (Range: 10 – 60 min), voltage (Range: 5 – 20 V), current (Range: 1 – 5A). Based on the experimental study, it is found that hardness removal to the desired extent could be achieved even for continuous flow EC reactor, so the use of it is found promising.

Keywords: hardness, continuous flow EC process, aluminum electrode, optimal operating parameters

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Authors: Faris Tarlochan, Siva Mahesh Tangutooru

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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

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Authors: K. S. Zaytsev, Y. R. Nartsissov

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Glycine is one of the key inhibitory neurotransmitters in Central nervous system (CNS) meanwhile glycinergic transmission is highly dependable on its appropriate reuptake from synaptic cleft. Glycine transporters (GlyT) of types 1 and 2 are the enzymes providing glycine transport back to neuronal and glial cells along with Na⁺ and Cl⁻ co-transport. The distribution and stoichiometry of GlyT1 and GlyT2 differ in details, and GlyT2 is more interesting for the research as it reuptakes glycine to neuron cells, whereas GlyT1 is located in glial cells. In the process of GlyT2 activity, the translocation of the amino acid is accompanied with binding of both one chloride and three sodium ions consequently (two sodium ions for GlyT1). In the present study, we developed a computer simulator of GlyT2 and GlyT1 activity based on known experimental data for quantitative estimation of membrane glycine transport. The trait of a single protein functioning was described using the probability approach where each enzyme state was considered separately. Created scheme of transporter functioning realized as a consequence of elemental steps allowed to take into account each event of substrate association and dissociation. Computer experiments using up-to-date kinetic parameters allowed receiving the number of translocated glycine molecules, Na⁺ and Cl⁻ ions per time period. Flexibility of developed software makes it possible to evaluate glycine reuptake pattern in time under different internal characteristics of enzyme conformational transitions. We investigated the behavior of the system in a wide range of equilibrium constant (from 0.2 to 100), which is not determined experimentally. The significant influence of equilibrium constant in the range from 0.2 to 10 on the glycine transfer process is shown. The environmental conditions such as ion and glycine concentrations are decisive if the values of the constant are outside the specified range.

Keywords: glycine, inhibitory neurotransmitters, probability approach, single protein functioning

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Authors: Khaled M. Ali, Ayman A. Mostafa, Soliman M. Soliman

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Objectives: To describe the most common clinical and endoscopic findings associated with complicated corneal ulcers in cats, and to determine the short-term outcomes after surgical treatment of these cats. Animals Eighteen client-owned cats of different breeds (52 females and 28 males), ranging in age from 3 months to 6 years, with corneal ulcers. Procedures: Cats were clinically evaluated to initially determine the concurrent corneal abnormalities. Endoscopic examination was performed to determine the anterior and posterior segments abnormalities. Superficial and deep stromal ulcers were treated using conjunctival flap. Corneal sequestrum was treated by partial keratectomy and conjunctival flap. Anterior synechia was treated via peripheral iridectomy and separation of the adhesion between the iris and the inner cornea. Symblepharon was treated by removal of the adhered conjunctival membrane from the cornea. Incurable endophthalmitis was treated surgically by extirpation. Short-term outcomes after surgical managements of selected corneal abnormalities were then assessed clinically and endoscopically. Results: Deep stromal ulcer with descemetocele, endophthalmitis, symblepharon, corneal sequestration and anterior synechia with secondary glaucoma and corneal scarring were the most common complications of corneal ulcer. FHV-1 was a common etiologic factor of corneal ulceration. Persistent corneal scars of varying shape and size developed in cats with deep stromal ulcer, anterior synechia, and corneal sequestration. Conclusions: Domestic shorthaired and Persian cats were the most predisposed breeds to FHV-1 infection and subsequent corneal ulceration. Immediate management of patients with corneal ulcer would prevent serious complications. No age or sex predisposition to complicated corneal ulceration in cats.

Keywords: cats, complicated corneal ulceration, clinical, endoscopic diagnosis, FHV-1

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Authors: E. A. Alaswad, H. M. Choudhry, F. Z. Filimban

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Sickle Cell Anemia (SCA) is one type of blood diseases related to autosomal disorder. The sickle shaped red blood cells are the main cause of many problems in the blood vessels and capillaries. Aerva Javanica (J) and Ficus Palmata (P) are medicinal plants that have many popular uses and have been proved their efficacy. The aim of this study was to assess the antioxidants activity and the antisickling effect of J and P extractions. The period of this study, air-dried leaves of J, and P plants were ground and the active components were extracted by maceration in water (W) and methanol (M) as solvents. The antioxidants activity of JW, PW, JM, and PM were assessed by way of the radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl (DPPH). To determine the antisickling effect of J and P extracts. 20 samples were collected from sickle cell anemia patients. Different concentrations of J and P extracts (200 and 110 μg/mL) were added on the sample and incubated. A drop of each sample was examined with light microscope. Normal and sickled RBCs were calculated and expressed as the percent of sickling. The stabilization effect of the extracts was measured by the osmotic fragility test for erythrocytes. The finding suggests as estimated by DPPH method, all the extracts showed an antioxidant activity with a significant inhibition of the DPPH radicals. PM has the least IC50% with 71.49 μg/ml while JM was the most with 408.49 μg/ml. Sickle cells treated with extracts at different concentrations significantly reduced the percentage of sickling compering to control samples. However, JM 200 μg/mL give the highest anti-sickling affect with 17.4% of sickling compared to control 67.5 of sickling while PM at 200 μg/mL showed the highest membrane cell stability. In a conclusion, the results showed that J and P extracts have antisickling effects. Therefore, the Aerva javanica and Ficus palmata may have a role in SCA management and a good impact on the patient's lives.

Keywords: Aerva javanica, antioxidant, antisickling, Ficus palmata, sickle cell anemia

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Guclu Insel, Efe Gumuslu, Gulten Yuksek, Nilay Sayi Ucar, Emine Ubay Cokgor, Tugba Olmez Hanci, Didem Okutman Tas, Fatos Germirli Babuna, Derya Firat Ertem, Okmen Yildirim, Ozge Erturan, Betul Kirci

Abstract:

In order to eliminate water scarcity problems, effective precautions must be taken. Growing competition for water is increasingly forcing facilities to tackle their own water scarcity problems. At this point, application of wastewater reclamation and reuse results in considerable economic advantageous. In this study, an enamel coating facility, which is one of the high water consumed facilities, is evaluated in terms of its wastewater reuse potential. Wastewater reclamation and reuse can be defined as one of the best available techniques for this sector. Hence, process and pollution profiles together with detailed characterization of segregated wastewater sources are appraised in a way to find out the recoverable effluent streams arising from enamel coating operations. Daily, 170 m³ of process water is required and 160 m³ of wastewater is generated. The segregated streams generated by two enamel coating processes are characterized in terms of conventional parameters. Relatively clean segregated wastewater streams (reusable wastewaters) are separately collected and experimental treatability studies are conducted on it. The results reflected that the reusable wastewater fraction has an approximate amount of 110 m³/day that accounts for 68% of the total wastewaters. The need for treatment applicable on reusable wastewaters is determined by considering water quality requirements of various operations and characterization of reusable wastewater streams. Ultra-filtration (UF), Nano-filtration (NF) and Reverse Osmosis (RO) membranes are subsequently applied on reusable effluent fraction. Adequate organic matter removal is not obtained with the mentioned treatment sequence.

Keywords: enamel coating, membrane, reuse, wastewater reclamation

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Authors: Dhara Shah, Chandrakant Shah

Abstract:

Construction industry utilizes plenty of water in the name of curing. Looking at the present scenario, the days are not so far when all construction industries will have to switch over to an alternative-self curing system, not only to save water for sustainable development of the environment but also to promote indoor and outdoor construction activities even in water scarce areas. At the same time, curing is essential for the development of proper strength and durability. IS 456-2000 recommends a curing period of 7 days for ordinary Portland cement concrete, and 10 to 14 days for concrete prepared using mineral admixtures or blended cements. But, being the last act in the concreting operations, it is often neglected or not fully done. Consequently, the quality of hardened concrete suffers, more so, if the freshly laid concrete gets exposed to the environmental conditions of low humidity, high wind velocity and high ambient temperature. To avoid the adverse effects of neglected or insufficient curing, which is considered a universal phenomenon, concrete technologist and research scientists have come up with curing compounds. Concrete is said to be self-cured, if it is able to retain its water content to perform chemical reaction for the development of its strength. Curing compounds are liquids which are either incorporated in concrete or sprayed directly onto concrete surfaces and which then dry to form a relatively impermeable membrane that retards the loss of moisture from the concrete. They are an efficient and cost-effective means of curing concrete and may be applied to freshly placed concrete or that which has been partially cured by some other means. However, they may affect the bond between concrete and subsequent surface treatments. Special care in the choice of a suitable compound needs to be exercised in such circumstances. Curing compounds are generally formulated from wax emulsions, chlorinated rubbers, synthetic and natural resins, and from PVA emulsions. Their effectiveness varies quite widely, depending on the material and strength of the emulsion.

Keywords: curing methods, self-curing compound, compressive strength, modulus of elasticity, durability

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

Abstract:

Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

Abstract:

Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: K. S. Sivakumaran, T. Thanga, B. Halabieh

Abstract:

The end panels of a large rectangular industrial duct, which experience significant internal pressures, also experience considerable transverse shear due to transfer of gravity loads to the supports. The current design practice of such thin plate panels for shear load is based on methods used for the design of plate girder webs. The structural arrangements, the loadings and the resulting behavior associated with the industrial duct end panels are, however, significantly different than those of the web of a plate girder. The large aspect ratio of the end panels gives rise to multiple bands of tension fields, whereas the plate girder web design is based on one tension field. In addition to shear, the industrial end panels are subjected to internal pressure which in turn produces significant membrane action. This paper reports a study which was undertaken to review the current industrial analysis and design methods and to propose a comprehensive method of designing industrial duct end panels for shear resistance. In this investigation, a nonlinear finite element model was developed to simulate the behavior of industrial duct end panel subjected to transverse shear and internal pressures. The model considered the geometric imperfections and constitutive relations for steels. Six scale independent dimensionless parameters that govern the behavior of such end panel were identified and were then used in an extensive parametric study. It was concluded that the plate slenderness dominates the shear strength of stockier end panels, and whereas, the aspect ratio and plate slenderness influence the shear strength of slender end panels. Based on these studies, this paper proposes design aids for estimating the shear strength of rectangular duct end panels.

Keywords: thin plate, transverse shear, tension field, finite element analysis, parametric study, design

Procedia PDF Downloads 222

Authors: Chaoran Liu

Abstract:

Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

Procedia PDF Downloads 233

Authors: Luksanaporn Krungkraipetch

Abstract:

Pterygium is a frequent ocular surface lesion that begins in the limbal conjunctiva within the palpebral fissure and spreads to the cornea. The lesion is more common in the nasal limbus than in the temporal, and it has a wing-like aspect. Indications for surgery, in decreasing order of significance, are growth over the corneal center, decreased vision due to corneal deformation, documented growth, sensations of discomfort, and esthetic concerns. The aim of this study is twofold: first, to determine the frequency of pterygium recurrence after surgery at the mentioned hospital, and second, to identify the factors that influence the recurrence of pterygium. The research design is a retrospective examination of 164 patient samples in an eastern Thai university hospital (Code 13766). Data analysis is descriptive statistics analysis, i.e., basic data details about pterygium surgery and the risk of recurrent pterygium, and for factor analysis, the inferential statistics chi-square and ANOVA are utilized. Twenty-four of the 164 patients who underwent surgery exhibited recurrent pterygium. Consequently, the incidence of recurrent pterygium after surgery was 14.6%. There were an equal number of men and women present. The participants' ages ranged from 41 to 60 years (62, 8 percent). According to the findings, the majority of patients were female (60.4%), over the age of 60 (51.2%), did not live near the beach (83.5%), did not have an underlying disease (92.1%), and 95.7% did not have any other eye problems. Gender (X² = 1.26, p = .289), age (X² = 5.86, p = .119), an address near the sea (X² = 3.30, p = .081)), underlying disease (X² = 0.54, p = .694), and eye disease (X² = 0.00, p = 1.00) had no effect on pterygium recurrence. Recurrences occurred in 79.1% of all surgical procedures and 11.6% of all patients using the bare sclera technique. The recurrence rate for conjunctival autografts was 20.9% for all procedures and 3.0% for all participants. Mitomycin-C and amniotic membrane transplant techniques had no recurrence following surgery. Comparing the surgeries done on people with recurrent pterygium did not show anything important (F = 1.13, p = 0.339). In conclusion, the prevalence of pterygium recurrence following pterygium, 14.6%, does not differ from earlier research. Underlying disease, other eye conditions, and surgical procedures such as pterygium recurrence are unaffected by pterygium surgery.

Keywords: pterygium, recurrence pterygium, pterygium surgery, excision pterygium

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Authors: Faisal A. Salih

Abstract:

Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

Procedia PDF Downloads 74

Authors: Suresh Kumar Verma, Jugal Kishore Das, Ealisha Jha, Mrutyunjay Suar, SKS Parashar

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In recent years nanoforms of inorganic metallic oxides has attracted a lot of interest due to their small size and significantly improved physical, chemical and biological properties compared to their molecular precursor. Some of the inorganic materials such as TiO2, ZnO, MgO, CaO, Al2O3 have been extensively used in biological applications. Zinc Oxide is a Wurtzite-type semiconductor and piezo-electric material exhibiting excellent electrical, optical and chemical properties with a band energy gap of 3.1-3.4 eV. Nanoforms of Zinc Oxide (ZnO) are increasingly recognised for their utility in biological application. The significant physical parameters such as surface area, particle size, surface charge and Zeta potential of Zinc Oxide (ZnO) nanoparticles makes it suitable for the uptake, persistance, biological, and chemical activities inside the living cells. The present study shows the effect of intrinsic defects of ZnO nanocrystals synthesized by high energy ball milling (HEBM) technique in their antibacterial activities. Bulk Zinc oxide purchased from market were ball milled for 7 h, 10 h, and 15 h respectively to produce nanosized Zinc Oxide. The structural and optical modification of such synthesized particles were determined by X-ray diffraction (XRD), Scanning Electron Microscopy and Electron Paramagnetic Resonance (EPR). The antibacterial property of synthesized Zinc Oxide nanoparticles was tested using well diffusion, minimum inhibitory Concentration, minimum bacteriocidal concentration, reactive oxygen species (ROS) estimation and membrane potential determination methods. In this study we observed that antibacterial activity of ZnO nanoparticles is because of the intrinsic defects that exist as a function of difference in size and milling time.

Keywords: high energy ball milling, ZnO nanoparticles, EPR, Antibacterial properties

Procedia PDF Downloads 428

Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

Abstract:

Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

Abstract:

Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

Procedia PDF Downloads 156

Authors: Nayira A. Abd Elbaky, Amal J. Fatani, Hazar Yaqub, Nouf M. Al-Rasheed, Naglaa El-Orabi, Mai Osman

Abstract:

The present work is aimed to evaluate the protective effect of N-acetyl cystiene (NAC), coenzyme Q10 (CoQ10), and their combination against carbon tetrachloride (CCl4)-induced cardiotoxicity in rats. CCl4 treatment significantly elevated the levels of cardiac oxidative stress bio markers including nitric oxide (NO) and malondialdehyde (MDA). A concomitant decrease in the level of reduced glutathione and the activity of membrane bound enzyme, calcium-adenosine triphosphatase were observed in the hearts of rats exposed to CCl4 compared to respective values in normal group. Quantitative analysis of myocardial energy metabolism revealed a significant decrease in the glucose content coupled with depletion in the activities of myocardial glycolytic enzymes as hexokinase (HK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) after CCl4 treatment. In addition, a significant elevation in myocardial hydroxyproline level was observed in CCl4 intoxicated rats indicating interstitial collagen accumulation. Pretreatment with either NAC, CoQ10 or their combination successively alleviated the alterations in myocardial oxidative stress and antioxidant markers, as well as effectively up-regulated the decrease in cardiac energetic biomarkers in CCl4 intoxicated rats. Moreover, these antioxidants markedly reduced myocardial hydroxyproline level versus that of CCl4-treated animals. In conclusion, the present results illustrated that the prophylactic use of the current antioxidant resulted in a remarkable cardioprotective effect against CCl4 induced myocardial damage, which suggest that they may candidates as prophylactic agents against different cardio-toxins.

Keywords: carbon tetrachloride, lipid peroxidation, antioxidant, energy metabolism, hydroxyproline

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