Search results for: hepatic impairment

Authors: Volkan Altintas, Burcu Oksuz

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Tourism industry essentially requires effective crisis management and crisis communication skills, as it is extremely vulnerable to crises. In terms of destinations, tourism crises cause dramatic decreases in the number of inbound tourists, impairment in the destination’s image, and decline in the level of preferability of the destination not only in the short but also in the long term. Therefore, any destination should be well prepared for crisis situation that may arise for various reasons. Currently, the advancement in communication technologies enables and facilitates information and experience to spread rapidly, and negative information and experiences tend to be shared to a further extent. Destinations are broadly exposed to the impacts of such communication stream. Turkey is almost continuously exposed to crises and their adverse impacts as a tourism destination, and thus requires effective crisis communication activities to be maintained. Hence, the approaches of tourism managers toward crisis communication and their proposals for addressing issues in question are important. This study intends to set forth the considerations of the managers serving in the tourism industry about crisis communication at destinations. The theoretical part of the study describes and explains crisis management and crisis communication at destinations; following which are provided the outcomes of the thorough in-depth interviews and discussions conducted for the establishment of the considerations of tourism managers. Managers indicated the role and importance of crisis communications in destinations.

Keywords: crisis communication, crisis management, destination, tourism managers

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Authors: Fatima Ali Abbass, Hassan Ibrahim Rkein

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The number of entities worldwide that currently accept digital currency as payment is increasing; however, digital currency still is not widely accepted as a medium of exchange, nor they represent legal tender. At the same time, this makes accounting for cryptocurrency, as cash (Currency) is not possible under IAS 7 and IAS 32, Cryptocurrency also cannot be accounted for as Financial Assets at fair value through profit or loss under IFRS 9. Therefore, this paper studies the possible means to account for Cryptocurrency, since, as of today, there is not yet an accounting standard that deals with cryptocurrency. The request to have a specific accounting standard is increasing from top accounting firms and from professional accounting bodies. This study uses a mixture of qualitative and quantitative analysis in its quest to explore the best possible way to account for cryptocurrency. Interviews and surveys were conducted targeting accounting professionals. This study highlighted the deficiencies in the current way of accounting for Cryptocurrency as intangible Assets with an indefinite life. The deficiency becomes well highlighted, as the asset will then be subject to impairment, where under GAAP, only depreciation in the value of the intangible asset is recognized. On the other hand, appreciation in the value of the asset is ignored, and this prohibits the reporting entity from showing the true value of the cryptocurrency asset. This research highlights the gap that arises due to using accounting standards that are not specific for Cryptocurrency and this study confirmed that there is an urgent need to call upon the accounting standards setters (IASB and FASB) to issue accounting standards specifically for Cryptocurrency.

Keywords: cryptocurrency, accounting, IFRS, GAAP, classification, measurement

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Authors: Leelavinothan Pari , Ayyasamy Rathinam

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Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

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Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Sarah Beaver, Renee Bryce

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Audiograms detect hearing impairment, but missing values pose problems. This work explores imputations in an attempt to improve accuracy. This work implements Linear Regression, Lasso, Linear Support Vector Regression, Bayesian Ridge, K Nearest Neighbors (KNN), and Random Forest machine learning techniques to impute audiogram frequencies ranging from 125Hz to 8000Hz. The data contains patients who had or were candidates for cochlear implants. Accuracy is compared across two different Nested Cross-Validation k values. Over 4000 audiograms were used from 800 unique patients. Additionally, training on data combines and compares left and right ear audiograms versus single ear side audiograms. The accuracy achieved using Root Mean Square Error (RMSE) values for the best models for Random Forest ranges from 4.74 to 6.37. The R\textsuperscript{2} values for the best models for Random Forest ranges from .91 to .96. The accuracy achieved using RMSE values for the best models for KNN ranges from 5.00 to 7.72. The R\textsuperscript{2} values for the best models for KNN ranges from .89 to .95. The best imputation models received R\textsuperscript{2} between .89 to .96 and RMSE values less than 8dB. We also show that the accuracy of classification predictive models performed better with our best imputation models versus constant imputations by a two percent increase.

Keywords: machine learning, audiograms, data imputations, single imputations

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as adipogenesis, insulin resistance, and inflammation. The present study aimed to test whether supplementation with African walnuts (Aw) could have an effect on adipogenesis and others dysfunctions associated with obesity in rats. Methods: Wistar rats were fed with standard diet (SD) or high-fat high-sucrose diet (HFS) and HFS with supplemented (HFS-Aw) for eight weeks. Results: HFS diet-induced body weight gain and increased fat mass compared to SD. In addition HFS-fed rats developed fasting hyperglycaemia and insulinaemia as well as insulin resistance. Aw supplementation in HFS rats had a protective effect against adipose tissues weigh gain but slightly against body weight gain and major study related disorders. This could be mainly due to decreased food intake dependently of effect in food intake in central nervous system, which decreased in HFS rats supplemented with African walnut compared to the HFS-diet group. Interestingly, African walnut supplementation induced a slight decrease of fasting glycaemia, insulinaemia and Nitric Oxide which could partially explain its minor protective effect against diet-induced insulin resistance. Additionally a decrease in hepatic TG and transaminases levels suggesting a protective effect against liver injury. Conclusion: Taken together these data suggested that supplementation of African walnut could be used to prevent adipose weight gain and related disorders on the other hand, minimally reduced insulin resistance.

Keywords: African walnut, dietary fiber, insulin resistance, oxidative stress

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Authors: Aya Gamal Khattab

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Chronic infection with the hepatitis C virus (HCV) is now the leading cause of liver-related morbidity and mortality; Currently, alanine aminotransferase ALT measurement is not only widely used in detecting the incidence, development, and prognosis of liver disease with obvious clinical symptoms, but also provides reference on screening the overall health status during health check-ups. Exercise is a low-cost, reliable and sustainable therapy for many chronic diseases. Low-volume high intensity interval training HIT is time efficient while also having wider application to different populations including people at risk for chronic inflammatory diseases. Purpose of this study was to investigate the effect of low volume high intensity interval training on ALT, AST in HCV patients. All practical work was done in outpatient physiotherapy clinic of Suez Canal Authority Hospitals. Forty patients both gender (27 male, 13 female), age ranged (40-60) years old submitted to low volume high intensity interval training on treadmill for two months three sessions per week. Each session consisting of five min warming up, two bouts for 10 min each bout consisting of 30 sec - 1 min of high intensity (75%-85%) HRmax then two to four min active recovery at intensity (40%-60%) HRmax, so the sum of high intensity intervals was one to two min for each session and four to eight min active recovery, and ends with five min cooling down. ALT and AST were measured before starting exercise session and 2 months later after finishing the total exercise sessions through blood samples. Results showed significant decrease in ALT, AST with improvement percentage (18.85%), (23.87%) in the study, so the study concluded that low volume high intensity interval training had a significant effect in lowering the level of circulating liver enzymes (ALT, AST) which means protection of hepatic cells and restoration of its function.

Keywords: alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C (HCV), low volume high intensity interval training

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Authors: Hanen Bouaziz-Ketata, Ghada Ben Salah, Hichem Ben Salah, Kamel Jamoussi, Najiba Zeghal

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The present study investigated the protective role of Hyparrhenia hirta on nitrate-induced liver damage. Experiments were carried out on adult rats divided into 3 groups, a control group and two treated groups. NaNO3 was administered daily by oral gavage at a dose of 400 mg/kg bw in treated groups either alone or coadministered with Hyparrhenia hirta methanolic extract via drinking water at a dose of 200 mg/kg bw for 50 days. Liver toxicity induced by NaNO3 was characterized by higher serum levels of glucose, total cholesterol and triglyceride and lower serum total protein than those of controls. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells’ damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, NaNO3 caused oxidant/antioxidant imbalance in the liver as reflected by the increased lipid peroxidation, the decreased total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities. Nitrate caused also a significant induction of DNA fragmentation as evidenced by the presence of a smear without ladder formation on agarose gel. Hyparrhenia hirta supplementation showed an improvement of all parameters cited above. We conclude that the present work provides ethnopharmacological relevance of Hyparrhenia hirta against the toxic effect of nitrate, suggesting its role as a potential antioxidant.

Keywords: Hyparrhenia hirta, liver, nitrate toxicity, oxidative stress, rat

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Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub

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This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.

Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening

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Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Jareeluk Ratanaphan

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The purposed of this research were; 1.To survey the teacher’s needs on knowledge about special education management for special needs learner 2.To development of distance training packages on providing for learner with special needs. 3. To study the effects of using the packages on trainee’s achievement. 4. To study the effects of using the packages on trainee’s opinion on the distance training packages. The design of the experiment was research and development. The research sample for survey were 86 teachers, and 22 teachers for study the effects of using the packages on achievement and opinion. The research instrument comprised: 1) training packages on special education management for special needs learner 2) achievement test 3) questionnaire. Mean, percentage, standard deviation, t-test and content analysis were used for data analysis. The findings of the research were as follows: 1. The teacher’s needs on knowledge about teaching for learner with learning disability, mental retardation, autism, physical and health impairment and research in special education. 2. The package composed of special education management for special needs student document and manual of distance training packages. The efficiency of packages was established at 79.50/81.35. 3. The results of using the packages were the posttest average scores of trainee’s achievement were higher than pretest. 4. The trainee’s opinion on the package was at the highest level.

Keywords: distance training, training package, teacher, learner with special needs

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Authors: Ajish K. Abraham

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Hearing aid is the most fundamental technology employed towards rehabilitation of persons with sensory neural hearing impairment. Hearing in noise is still a matter of major concern for many hearing aid users and thus continues to be a challenging issue for the hearing aid designers. Several techniques are being currently used to enhance the speech at the hearing aid output. Most of these techniques, when implemented, result in reduction of intelligibility of the speech signal. Thus the dissatisfaction of the hearing aid user towards comprehending the desired speech amidst noise is prevailing. Multichannel Wiener Filter is widely implemented in binaural hearing aid technology for noise reduction. In this study, Wiener filter based noise reduction approach is experimented for a single microphone based hearing aid set up. This method checks the status of the input speech signal in each frequency band and then selects the relevant noise reduction procedure. Results showed that the Wiener filter based algorithm is capable of enhancing speech even when the input acoustic signal has a very low Signal to Noise Ratio (SNR). Performance of the algorithm was compared with other similar algorithms on the basis of improvement in intelligibility and SNR of the output, at different SNR levels of the input speech. Wiener filter based algorithm provided significant improvement in SNR and intelligibility compared to other techniques.

Keywords: hearing aid output speech, noise reduction, SNR improvement, Wiener filter, speech enhancement

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Authors: Malinda Sabrina, Khoerul Anwar

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Railway noise generated by pass-by train has been described as a form of environmental pollutants especially for the residential area near the railway. Many studies have shown, that environmental noise particularly transportation noise has negative effects on people which resulting in annoyance and specific health problems such as cardiovascular disease, cognitive impairment and sleep disturbance. Therefore, various attempts are made to reduce the noise. One method of reducing such noise to acceptable noise levels is to build acoustically barrier walls. The objective of this study was to review the method of reducing railway noise and obtain the preliminary design of the acoustics barrier on the edge of railway tracks close to the residential area. The design of this barrier is using the Maekawa's method. Measurements have been performed in residential areas around the railroads in the Karawang - Indonesia with the absence of an acoustical barrier. From the observation, it was found that the railway was passed by five trains within thirty minutes. With the limited distance between the railway tracks and the location of the residential area as well as the street of residents, then it was obtained that a reduction in sound pressure level is 25 dBA. Maximum sound pressure level obtained is 86.9 dBA then by setting the barrier as high as 4 m at a distance, 2.5 m from the railway, the noise level received by residents in the settlement around the railway line becomes 61.9 dBA.

Keywords: acoustics barrier, Maekawa's method, noise attenuation, railway noise

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Authors: Sophio Kalmakhelidze, Eka Shekiladze, Tamar Sanikidze, Mikheil Gogebashvili, Nazi Ivanishvili

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Radiation-induced various degrees of brain injury and cognitive impairment have been described after cranial radiotherapy of brain tumors. High doses of ionizing radiation have a severe impact on the central nervous system, resulting in morphological and behavioral impairments. Structures of the limbic system are especially sensitive to radiation exposure. Hence, compounds or drugs that can reduce radiation-induced impairments can be used as promising antioxidants or radioprotectors. In our study Mice whole-body irradiation with 137Cs was performed at a dose rate of 1,1 Gy/min for a total dose of 5 Gy with a “Gamma-capsule-2”. Irradiated mice were treated with Herniarin (20 mg/kg) for five days before irradiation and the same dose was administrated after one hour of irradiation. The immediate and delayed effects of ionizing radiation, as well as, protective effect of Herniarin was evaluated during early and late post-irradiation periods. The results reveal that ionizing radiation (5 Gy) alters the structure of the hippocampus in adult mice during the late post-irradiation period resulting in the decline of memory formation and learning process. Furthermore, Simple Coumarin-Herniarin reveals a radiosensitizing effect reducing morphological and behavioral alterations.

Keywords: ionizing radiation, cognitive impairments, hippocampus, limbic system, Herniarin

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Authors: Sara Arafeh, Kovriguine Evguine

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Cytochromes P450 are enzymes that require a supply of electrons to catalyze the synthesis of steroid hormones, fatty acids, and prostaglandin hormone. Cytochrome P450 Oxidoreductase (CYPOR), a membrane bound enzyme, provides these electrons in its open conformation. CYPOR has two cytosolic domains (FAD domain and FMN domain) and an N-terminal in the membrane. In its open conformation, electrons flow from NADPH, FAD, and finally to FMN where cytochrome P450 picks up these electrons. In the closed conformation, cytochrome P450 does not bind to the FMN domain to take the electrons. It was found that when the cytosolic domains are isolated, CYPOR could not bind to cytochrome P450. This suggested that the membrane environment is important for CYPOR function. This project takes the initiative to better understand the dynamics of CYPOR in its full length. Here, we determine the distance between specific sites in the FAD and FMN binding domains in CYPOR by Forster Resonance Energy Transfer (FRET) and Ultrafast TA spectroscopy with and without NADPH. The approach to determine these distances will rely on labeling these sites with red and infrared fluorophores. Mimic membrane attachment is done by inserting CYPOR in lipid nanodiscs. By determining the distances between the donor-acceptor sites in these domains, we can observe the open/closed conformations upon reducing CYPOR in the presence and absence of cytochrome P450. Such study is important to better understand CYPOR mechanism of action in various endosomal membranes including hepatic CYPOR which is vital in plasma cholesterol homeostasis. By investigating the conformational cycles of CYPOR, we can synthesize drugs that would be more efficient in affecting the steroid hormonal levels and metabolism of toxins catalyzed by Cytochrome P450.

Keywords: conformational cycle of CYPOR, cytochrome P450, cytochrome P450 oxidoreductase, FAD domain, FMN domain, FRET, Ultrafast TA Spectroscopy

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Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin

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Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.

Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease

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Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

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K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

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Authors: Ezzati Givi M., Ezzatigivi N., Eimani H.

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Trigeminal Neuralgia (TN) consists of painful attacks often triggered with general activities, which cause impairment and disability. The first line of treatment consists of pharmacotherapy. However, the occurrence of many side-effects limits its application. Acute pain relief is crucial for titrating oral drugs and making time for neurosurgical intervention. This study aimed to examine the long-term anesthetic effect of QX-314 and capsaicin in trigeminal neuralgia using an animal model. TN was stimulated by surgical constriction of the infraorbital nerve in rats. After seven days, anesthesia infiltration was done, and the duration of mechanical allodynia was compared. Thirty-five male Wistar rats were randomly divided into seven groups as follows: control (normal saline); lidocaine (2%); QX314 (30 mM); lidocaine (2%)+QX314 (15 mM); lidocaine (2%)+QX314 (22 mM); lidocaine (2%)+QX314 (30 mM); and lidocaine (2%)+QX314 (30 mM) +capsaicin (1μg). QX314 in combination with lidocaine significantly increased the duration of anesthesia, which was dose-dependent. The combination of lidocaine+QX314+capsaicin could significantly increase the duration of anesthesia in trigeminal neuralgia. In the present study, we demonstrated that the combination of QX-314 with lidocaine and capsaicin produced a long-lasting, reversible local anesthesia and was superior to lidocaine alone in the fields of the duration of trigeminal neuropathic pain blockage.

Keywords: trigeminal neuralgia, capsaicin, lidocaine, long-lasting

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Asiri Wijesinghe, N. D. Kodikara, Damitha Sandaruwan

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The Diabetic Retinopathy (DR) is a rapidly growing interrogation around the world which can be annotated by abortive metabolism of glucose that causes long-term infection in human retina. This is one of the preliminary reason of visual impairment and blindness of adults. Information on retinal pathological mutation can be recognized using ocular fundus images. In this research, we are mainly focused on resurrecting an automated diagnosis system to detect DR anomalies such as severity level classification of DR patient (Non-proliferative Diabetic Retinopathy approach) and vessel tortuosity measurement of untwisted vessels to assessment of vessel anomalies (Proliferative Diabetic Retinopathy approach). Severity classification method is obtained better results according to the precision, recall, F-measure and accuracy (exceeds 94%) in all formats of cross validation. In ROC (Receiver Operating Characteristic) curves also visualized the higher AUC (Area Under Curve) percentage (exceeds 95%). User level evaluation of severity capturing is obtained higher accuracy (85%) result and fairly better values for each evaluation measurements. Untwisted vessel detection for tortuosity measurement also carried out the good results with respect to the sensitivity (85%), specificity (89%) and accuracy (87%).

Keywords: fundus image, exudates, microaneurisms, hemorrhages, tortuosity, diabetic retinopathy, optic disc, fovea

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Authors: Ali Kassem, Aly Taha, Abeer Hassan, Kazuhide Higuchi

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Introduction: Trans arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is usually followed by hepatic dysfunction that limits its efficacy. L-carnitine is recently studied as hepatoprotective agent. Our aim is to evaluate the L-carnitine effects against the deterioration of liver functions after TACE. Method: 53 patients with intermediate stage HCC were assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and control group (27 patients) without L-carnitine therapy. 28 of studied patients received branched chain amino acids granules. Results: There were significant differences between L-carnitine Vs. control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited improvement at 4 weeks after TACE (p < 0.01 Vs 1 week after TACE). Control group has significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). L-carnitine displayed improvement in (PT) from baseline to 1 week, 4 w (p < 0.05) and 12 weeks after TACE. PT in control group declined less than baseline along all follow up intervals. Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, it significantly increased at 1 week (p = 0.01). ALT and C-reactive protein elevation were suppressed at 1 week after TACE in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. Conclusion: L-carnitine and BCAA combination therapy offer a novel supportive strategy after TACE in HCC patients.

Keywords: hepatocellular carcinoma, L-carnitine, liver functions , trans-arterial embolization

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Authors: Magdalena Barbara Kaziuk, Ilona Hubner, Jacek Hubner, Slawomir Kroczka

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Background: The motor neuron disease is a progressive neurodegenerative disease causing malfunction. Irrespective of the form of the disease and its onset always leads to the worsening of the quality of life, with patients usually depending on the family. Materials and methods: The study included 20 persons (5 females, 15 males, aged 65,5 ± 20 years) with clinically certain or probable diagnosis of the motor neuron disease. Patients were examined three times in the period of six months. The diagnosis was established based on the criteria of El Escorial. Manual dexterity was assessed using the test of the card Rene Zazzo and the test of shading in with lines Mira Stambak. Results: All patients achieved unsatisfactory results in Rene Zazzo’s test of the card and most of the patients (60%) in Mira Stambak’s test of shading with lines. Significantly higher test results were achieved for Rene Zazzo’s test and lower test results for Mira Stambak’s test in consecutive measurements. Conclusions: Impairment of manual dexterity is present already at the moment of diagnosing the disease and is growing significantly during its course. The quality of life for MND patients undergoes gradual deterioration as a result of the malfunction.

Keywords: manual dexterity, motor neuron disease, quality of life, malfunction

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Authors: Abdulaziz Alkathiry

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Concussion is a common brain injury that affect physical and cognitive performance. While several studies indicated that adolescents are more likely to develop concussion, in the last decade concussion has been mainly explored in adults. Migraine has been identified as a common symptom reported after concussion and was tied with worse prognoses. Hence, we aimed to investigate the effect of migraine on functional performance and self-reported symptoms in children with concussion. This cross-sectional study involved 35 symptomatic children aged 9 – 17 years recruited within 1 year from their concussion injury at a tertiary balance center. Participants’ symptoms and functional performance were assessed using the post-concussion symptoms scale (PCSS) and the functional gait assessment (FGA) respectively. Concussed children with migraine showed significantly worse symptoms including fatigue, sleeping impairment, difficulty concentrating, and visual problems (P < 0.05). Functional performance didn’t show differences between concussed children with and without migraine. Although concussed children with and without migraine didn’t show any differences on functional performance, worse cognitive symptoms were found in concussed children with migraine. A customized treatment approach is indicated in the presence of migraine for the management of children with concussion. Keywords: Concussion; Migraine; Balance; Post-Concussion Symptoms Scale; Functional Gait Assessment

Keywords: concussion, migraine, post-concussion symptoms scale, functional gait assessment, balance

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Authors: Tabussam Tufail

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Purpose: The core purpose of the current review article is to elaborate the phytochemicals present in turnip (brassica rapus l.) and also allied health claims. Plant-based foods contain a significant amount of bioactive compounds which provide desirable health benefits beyond the basic nutrition. Epidemiological evidence suggests that consumption of a diet rich in vegetables and fruits has positive implications for human health. Design: Potential of turnip peroxidase (TP) for the treatment of phenolic-contaminated solutions has been reviewed. However, issues of taste along with behavioral nutrition ought to be considered. So in the last decades, special attention has been paid towards edible plants, especially those that are rich in secondary metabolites (frequently called phytochemicals) and nowadays, there is an increasing interest in the antioxidant activity of such phytochemicals present in the diet. These chemicals favor nutritional and phytotherapy that is emerging as new concepts of health aid in recent years. Turnip is rich in these valuable ingredients though it can be employed as having health promoting and healing properties. Findings: Numerous bioactive components i.e. organic acids, phenolic compounds, turnip peroxidase, kaempeferol, vitamin-K, etc. are present in turnip. The review focused on the significance of plant derived (especially turnip) phenolic compounds as a source of certain beneficial compounds for human health. Owing to the presence of bioactive moieties, the turnip has high antioxidant activity, positive role in blood clotting, effectual in phenobarbital-induced sleeping time, effective against hepatic injury in diabetics and also have a good hepatoprotective role. Strong recommendations for consumption of nutraceuticals from turnip have become progressively popular to improve health, and to prevent from diseases.

Keywords: phytochemicals, turnip, antioxidants, health benefits

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Authors: Si On Na

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The development of American radio and print media since World War II has allowed people with disabilities to engage more directly with the public, gradually changing the perception that disabled people constitute a kind of social impairment or burden. People with disabilities have rarely been portrayed as equal to the non-disabled. In the postwar period, a dramatic shift from eugenicist conceptualizations of disability and widespread institutionalization gradually evolved into conditions of greater openness in public discourse. This discourse was marked at mid-century by telethons and news media (both print and television) which sought to commodify people with disabilities for commercial gain through stories that promoted alienating forms of empowerment alternating with paternalistic pity. By comparing studies of the history of American disability advocacy in the twentieth century and the evolution of the image of disability characteristic of mid-century media discourse, this paper will examine the relationship between the passage of the American with Disabilities Act of 1990 (ADA) and the expanded media representation of people with disabilities. This paper will argue that the legal mandate of the ADA ultimately transformed the image of people with disabilities from those who are weak and in need of support to viable consumers, encouraging traditional American print, film, and television media outlets to solicit the agency of people with disabilities in the authentic portrayal of themselves and their disabilities.

Keywords: ADA, disability representation, media portrayal, postwar United States

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Authors: Marlyn Mathew

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Communication is the key factor in any vocational /job set-up. However many persons with disabilities suffer a deficit in this very area in terms of comprehension, expression and cognitive skills making it difficult for them to get employed appropriately or stay employed. Vocational Rehabilitation is a continuous and coordinated process which involves the provision of vocational related services designed to enable a person with disability to obtain and maintain employment. Therefore the role of the speech language pathologist is crucial in assessing the communication deficits and needs of the individual at the various phases of employment- right from the time of seeking a job and attending interview with suitable employers and also at regular intervals of the employment. This article discusses the various communication deficits and the obstacles faced by individuals with special needs including but not limited to cognitive- linguistic deficits, execution function deficits, speech and language processing difficulties and strategies that can be introduced in the workplace to overcome these obstacles including use of visual cues, checklists, flow charts. The paper also throws light on the importance of educating colleagues and work partners about the communication difficulties faced by the individual. This would help to reduce the communication barriers in the workplace, help colleagues develop an empathetic approach and also reduce misunderstandings that can arise as a result of the communication impairment.

Keywords: vocational rehabilitation, disability, speech language pathologist, cognitive, linguistics

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Authors: Tsoi Kim Ming, Yu King Pong

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Background: With powered wheelchair, patients can travel more easily and conveniently. However, some patients suffer from other difficulties, such as visual impairment, cognitive disorder, or psychological issues, which make them unable to control powered wheelchair safely. Purpose: Therefore, those patients are required to complete a comprehensive driving training by therapists on confined area, which simulates narrow paths in daily live. During the training, therapists will give series of driving instruction to patients, which may be unaware of patients crossing out the boundary of area. To facilitate the training, it is needed to develop a device to provide warning to patients during training Method: We adopt LIDAR for distance sensing started from center of confined area. Then, we program the LIDAR with linear geometry to remember each side of the area. The LIDAR will sense the location of wheelchair continuously. Once the wheelchair is driven out of the boundary, audio alert will be given to patient. Result: Patients can pay their attention to the particular driving situation followed by audio alert during driving training, which can learn how to avoid out of boundary in similar situation next time. Conclusion: Instead of only instructed by therapist, the LIDAR can facilitate the powered wheelchair training by patients actively pay their attention to driving situation. After training, they are able to control the powered wheelchair safely when facing difficult and narrow path in real life.

Keywords: PWC, training, rehab, AT

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Authors: Folajinmi Oluwasina, Greg Abiaziem, Moses Luke, Mobolaji Kolawole, Nancy Yibowei, Anne Taiwo

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Background: Occurrence of HIV infection has an adverse effect on the natural causes of Hepatitis B Viral (HBV) infection, faster progression of hepatic fibrosis demonstrated in patients with co-infection. This study was carried out to determine the incidence of HBV infection among HIV-positive patients, and to retrospectively evaluate laboratory characteristics of patients with HIV/HBV co-infection. Methods: A retrospective analysis of patient files for all HIV-infected cases followed-up and treated at 52 health facilities. Among HIV-infected cases, those with HBsAg positivity and HIV/Hepatitis B co-infection were determined. Socio demographic, alcohol or substance use, ART, CD4, Viral Load levels and treatment durations were retrospectively evaluated. Results: Of the 125 HIV-infected patients evaluated retrospectively, 17 (13.6%) had HBsAg positivity. Of these 17 cases were 11(64.7%) male and 6 (35.3%) female, with a mean age of 48.7 years. No patients had a history of alcohol or substance use. The mean duration of follow up was 28 months. 9 (52.9%) patients had negative HBV DNA at presentation while 8(47%) had positive HBV DNA, with normal ALT levels in all subjects. Among the 9 cases with negative HBV DNA who had no indication for the treatment of chronic hepatitis B. In five cases, treatment was commenced since HBV DNA was elevated in conjunction with low CD4. One patient in whom treatment was not indicated based on HBV DNA and CD4 levels in conjunction with the absence of AIDS defining clinical picture was currently being followed-up without treatment. Of the patients receiving HAART therapy, the average CD4 count at presentation was 278 cells/mm3 vs. 466 cells/mm3 at the end of 12 months. In three subjects with positive HBV DNA, a decrease in HBV DNA was noted after initiation of treatment. In four patients with negative DNA who received treatment, the HBV DNA negative status was found to remain, while one patient who did not receive treatment had elevated HBV DNA and decreased CD4 levels. Conclusion: It was shown that this group of patients with HIV/HBV co-infection, HAART was found to be associated with a decrease in HBV DNA in HBV DNA positive cases, absence of transition to positivity among those with negative HBV DNA, and with increased CD4 in all subjects.

Keywords: Hepatitis B, DNA, anti retroviral therapy, co-infection

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Authors: J. B. Minari, O. B. Oloyede, A. A. Odutuga

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Myeloperoxidase is the most abundant enzyme found in the polymorphonuclear neutrophil and is known to play a central role in the host defense system of the leukocyte. The enzyme has been reported to interact with some drugs to generate free radical which inhibits its activity. This study investigated the effects of artesunate on the activity of the enzyme and the subsequent effect on the host immune system. In investigating the effects of the drugs on myeloperoxidase, the influence of concentration, pH, partition ratio estimation and kinetics of inhibition were studied. This study showed that artesunate is concentration-dependent inhibitor of myeloperoxidase with an IC50 of 0.078mM. Partition ratio estimation showed that 60 enzymatic turnover cycles are required for complete inhibition of myeloperoxidase in the presence of artesunate. The influence of pH on the effect of artesunate on the enzyme showed least activity of myeloperoxidase at physiological pH. The kinetic inhibition studies showed that artesunate caused a competitive inhibition with an increase in the Km value from 0.12mM to 0.26mM and no effect on the Vmax value. The Ki value was estimated to be 2.5mM. The results obtained from this study show that artesunate is a potent inhibitor of myeloperoxidase and it is capable of inactivating the enzyme. It is considered that the inhibition of myeloperoxidase in the presence of artesunate as revealed in this study may partly explain the impairment of polymorphonuclear neutrophil and consequent reduction of the strength of the host defense system against secondary infections.

Keywords: myeloperoxidase, artesunate, inhibition, nuetrophill

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