Search results for: group administration

Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

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Background: The use of nanoparticles for medication delivery offers the possibility of avoiding the negative effects of systemic antibiotic dosing as well as antibiotic resistance in bacteria. Aim of the study: The goal of this study was to see the efficiency of local administration of tetracycline loaded on nano chitosan in the treatment of the induced infection of the albino rats gingiva with Porphyromonas gingivalis through Immunohistochemical localization of Interleukin-1beta (IL-1β) as a proinflammatory cytokine.Material and methods: Fifty adult male albino rats 150 - 180 grams body weight used in this investigation. Any changes in rats’ weights were detected. The male albino rats were divided haphazardly into five groups as Group I involved ten rats; they served as a normal negative control group. Group II involved ten rats; they were infected once with P.gingivalis that was injected into the interdental gingiva. Group III involved ten rats; they were subjected to the same procedure as group II and then to daily injection at the site of infection with diluted tetracycline powder. Group IV involved ten rats; they were subjected to the same procedure as group II and then to daily injection of nano Chitosan at the site of injection. Group V involved ten rats; they were subjected to the same procedure as group II and then to daily injection of tetracycline loaded on nano Chitosan at the site of injection. After rats had been euthanized, the extraction and preparation of their gingiva were carried out in order to examine histologically and immunohistochemically. Results: The light microscopic results of groups II, III, and IV showed degeneration represented by swollen epithelial cells, collagen fibers dissociation of the connective tissue of lamina propria, and areas of basement membrane discontinuation, while groups I and V showed an almost normal histological picture of gingival tissue. Immunohistochemical results showed a significant difference in Group II and III when compared to control. No significant difference appears in group V when compared to the control (group I). Conclusion: Using nanochitosan as a carrier for tetracycline is a new technology to get over the increasing resistance of tetracycline.

Keywords: immunohistochemistry, P.gingivalis, nano-chitosan, tetracycline, periodontitis

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Authors: Vahid Changizi, Aram Rostami, Akbar Mosavi

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Purpose of study: Critical macromolecules of cells such as DNA are in exposure to damage of free radicals that induced from interaction of ionizing radiation with biological systems. Selenium and vitamin-E are natural compound that has been shown to be a direct free radical scavenger. The aim of this study was to investigate the in vivo/in vitro radioprotective effect of selenium and vitamin-E separately and synergistically against genotoxicity induced by 6MV x-rays irradiation in cultured blood lymphocytes from 15 human volunteers. Methods: Fifteen volunteers were divided in three groups include A, B and C. These groups were given slenium(800 IU), vitamin-E(100 mg) and selenium(400 IU) + vitamin-E(50 mg), respectively. Peripheral blood samples were collected from each group before(0 hr) and 1, 2 and 3 hr after selenium and vitamin-E administration (separately and synergistically). Then the blood samples were irradiated to 200 cGy of 6 Mv x-rays. After that, lymphocyte samples were cultured with mitogenic stimulation to determine the chromosomal aberrations wih micronucleus assay in cytokinesis-blocked binucleated cells. Results: The lymphocytes in the blood samples collected at 1 hr after ingestion selenium and vitamin-E, exposed in vitro to x-rays exhibited a significant decrease in the incidence of micronuclei, compared with control group at 0 hr. The maximum protection and decrease in frequency of micronuclei(50%) was observed at 1 hr after administration of selenium and vitamin-E synergistically. Conclusion: The data suggest that ingestion of selenium and vitamin-E as a radioprotector substances before exposures may reduce genetic damage caused by x-rays irradiation.

Keywords: x-rays, selenium, vitamin-e, lymphocyte, micronuclei

Procedia PDF Downloads 247

Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

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Authors: Mathumalar Loganathan, Lina Syazana, Bryony Dean Franklin

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Background: The therapeutic benefit of self-administered medication for long-term use is limited by an average 50% non-adherence rate. Patient forgetfulness is a common factor in unintentional non-adherence. With a growing ageing population, strategies to improve self-administration of medication adherence are essential. Our aim was to review systematically the effects of interventions to optimise self-administration of medication. Method: Database searched were MEDLINE, EMBASE, PsynINFO, CINAHL from 1980 to 31 October 2013. Search terms included were ‘self-administration’, ‘self-care’, ‘medication adherence’, and ‘intervention’. Two independent reviewers undertook screening and methodological quality assessment, using the Downs and Black rating scale. Results: The search strategy retrieved 6 studies that met the inclusion and exclusion criteria. Three intervention strategies were identified: self-administration medication programme (SAMP), nursing education and medication packaging (pill calendar). A nursing education programme focused on improving patients’ behavioural self-management of drug prescribing. This was the most studied area and three studies highlighting an improvement in self-administration of medication. Conclusion: Results are mixed and there is no one interventional strategy that has proved to be effective. Nevertheless, self-administration of medication programme seems to show most promise. A multi-faceted approach and clearer policy guideline are likely to be required to improve prescribing for these vulnerable patients. Mixed results were found for SAMP. Medication packaging (pill calendar) was evaluated in one study showing a significant improvement in self-administration of medication. A meta-analysis could not be performed due to heterogeneity in the outcome measures.

Keywords: self-administered medication, intervention, prescribing, older patients

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Authors: Venkatgiri, Ranganath, L. Nagaraja, B. N. Sagar Pandav, S. M. Usturge, D. Dilipkumar, B. V. Shivprakash, B. Bhagwanthappa, D. Jahangir

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A comparative evaluation of Tramadol and Pentazocine as a pre-emptive analgesic in clinical cases of female dogs undergoing ovariohysterectomy was undertaken during this study. During the study, the following parameters were assessed viz., Rectal temperature (ᵒF), Respiratory rate (breaths/min) and Heart rate (beats/min). Hematological and biochemical parameters viz., total erythrocyte count (TEC) (millions/cmm), hemoglobin (g %), otal leucocytes count (TLC) (thousands/cmm), differential leucocytes count (DLC) (%), serum creatinine (mg/dl), plasma protein (mg/dl), blood glucose (mg/dl) was estimated before the surgery and after administration of general anaesthesia and immediate postoperative periods of 0, 12 and 24 hr respectively. Mean Total Pain Score (MTPS) includes measurement of parameters like posture, vocalization, activity level, response to palpation and agitation at different intervals was calculated before surgery and after administration of general anesthesia and post-operative periods of 1, 2, 4, 6, 12hrs and 24 hrs respectively. Mean Total Pain Score (MTPS) was given for each parameter (Posture, Vocalization, Activity Level, Response to Palpation and Agitation) like 0,1,2,3. (maximum score will be given was 4.). Results were revealed in all three groups including control group. There were significant minor alterations in physiological, hematological and biochemical parameters. MTPS (mean total pain score) were revealed and found a significant alteration when compared with control group. In conclusion, Tramadol found to be a better analgesic and had up to 8hrs of analgesic effect and Pentazocine is superior in post-operative pain management when compared to Tramadol because this group of dogs experienced less surgical stress, consumed less anesthetic dose, they recovered early, and they had less MTPS score.

Keywords: dog, pentazocine, tramadol, ovariohysterectomy

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Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

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Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Siyu Wang, Anthony Ward

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Emotional intelligence (EI) is a well-established personal characteristic. It has been viewed as a critical factor which can influence an individual's academic achievement, ability to work and potential to succeed. When working in a group, EI is fundamentally connected to the group members' interaction and ability to work as a team. The ability of a group member to intelligently perceive and understand own emotions (Intrapersonal EI), to intelligently perceive and understand other members' emotions (Interpersonal EI), and to intelligently perceive and understand emotions between different groups (Cross-boundary EI) can be considered as Group emotional intelligence (Group EI). In this research, a more representative Group EI measurement approach, which incorporates the information of the composition of a group and an individual’s role in that group, is proposed. To demonstrate the claim of being more representative Group EI measurement approach, this study adopts a multi-method research design, involving a combination of both qualitative and quantitative techniques to establish a metric of Group EI. From the results, it can be concluded that by introducing the weight coefficient of each group member on group work into the measurement of Group EI, Group EI will be more representative and more capable of understanding what happens during teamwork than previous approaches.

Keywords: case study, emotional intelligence, group EI, multi-method research

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Authors: Huraizah Arshad, Maizan Baba

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Malaysia is the country that consists of high population of Muslim community with more than 60%; as reported in year 2014. The stability of economy allowed people to contribute towards ongoing charity such as waqf and infaq. Waqf is an important component of the Islamic economic instruments since it is beneficial to help those needy in the community. Although waqf had been implemented in Malaysia for many years, there is no specific framework on how to manage and maintain the waqf properties in effective and efficient practice. Thus, a comprehensive framework related to the management and maintenance of the waqf properties is crucial to ensure that the administration of the fund is fair within the community. The objective of this article is to examine the related literatures in administration, management and maintenance of waqf for the past ten (10) years. The methodology of this article is through qualitative research based on literature on waqf administration and management; waqf planning and development and the application of maintenance concept. Data from each articles related in this field were collected and statistically analyzed using the SPSS software. A variable such as authorship patterns, number of articles published and geographical affiliation are identified in this study. The general finding in this article shows that there are still limited number of articles and papers published by the researchers related to this field. Henceforth, this article provides significant suggestions and strategies for the future research on waqf administration, management and maintenance.

Keywords: Waqf, administration and management, maintenance, improvement, facilities management

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Authors: R. Prinsloo

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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Authors: Yi-Ting Liu, Pei-Ying Wen

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In order to improve the overall safety of chemotherapy, safety-protecting net was established for the whole process from prescribing by physicians, transcribing by nurses, dispensing by pharmacists to administering by nurses. The information system was used to check and monitor whole process of administration and related sheets were computerized to simplify the paper work.

Keywords: chemotherapy, bar code medication administration, medication safety

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Authors: Sabrina Sebbane, Alina Elena Parvu

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Introduction: Santolina rosmarinifolia is a plant of the Santolina genus, a family made of medicinal plants widely used. Some of the Santolina species have been proven to have potent anti-inflammatory and anti-oxidant effects. However, no in vivo study has been made to demonstrate this in Santolina rosmarinifolia. The aim of our study is to experimentally evaluate the potential anti-inflammatory and anti-oxidant effects of Santolina rosmarinifolia plant extracts on acute inflammation in rats. These effects are defined by measuring the modifications on nitric oxide, reactive oxygen species and anti-oxidant response in serum. Materials and Methods: Rats were divided into 5 groups (n=6). Three groups were given Santolina rosmarinifolia extract by gavage in different concentrations(100%, 50%, 25%) for a week. Inflammation was induced by i.m injection of turpentine oil on the 8th day. One group was only given turpentine oil and the fifth group acted as control and was given only saline solution. Blood was collected and serum separated. Global tests were used to measure the oxidative stress, total oxidative status (TOS), total antioxidant reactivity (TAR) and the modified method of Griess assay to measure NO synthesis. Malondilaldehyde (MDA) and thiols levels were also assessed. Results: Santolina rosmarinifolia did not significantly change the TOS levels (p > 0.05). Santolina rosmarinifolia 25% and 50% decreased significantly the TAR levels (p < 0.001). Santolina 100% didn't have a significant effect on TAR (p > 0.05). All concentrations of Santolina rosmarinifolia increased the oxidative stress index (OSI) significantly(p < 0.05). Santolina rosmarinifolia 100% significantly decreased NO synthesis (p value < 0.05). In the diluted Santolina groups, no significant effect on NO synthesis was observed. In the groups treated with Santolina 100% and Santolina rosmarinifolia 50%, thiols concentration were significantly higher compared to the inflammation group (p < 0.02). A higher stimulatory effect was found in the Santolina 25% group (p value < 0.05). MDA levels were not significantly modified by the administration of Santolina rosmarinifolia (p > 0.05). Conclusion: All three solutions of Santolina rosmarinifolia had no important effect on oxidant production. However, Santolina rosmarinifolia solutions had a positive effect by increasing the thiols concentration in the serum of the models. The sum of all the effects produced by the administration of Santolina did not show a significant decrease of nitro-oxidative stress. Further experiments including smaller concentrations of Santolina rosmarinifolia will be made. Santolina rosmarinifolia should also be tested as a curative treatment.

Keywords: inflammation, MDA, nitric oxide, santolina rosmarinifolia, thiols, TAR, TOS

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Authors: Mohammad Hadi Mahmoodi, Elahe Saedpanah

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Since pronunciation is among those factors that can have strong effects on EFL learners’ successful communication, instructional programs with accurate pronunciation purposes seem to be a necessity in any L2 teaching context. The widespread use of smart mobile phones brings with itself various educational applications, which can assist foreign language learners in learning and speaking another language other than their L1. In line with this supportive innovation, the present study investigated the role of LDOCE (Longman Dictionary of Contemporary English), a mobile application, on improving Iranian EFL learners’ pronunciation accuracy. To this aim, 40 EFL learners studying English at the intermediate level participated in the current study. This was an experimental research with two groups of 20 students in an experimental and a control group. The data were collected through the administration of a pronunciation pretest before the instruction and a post-test after the treatment. In addition, the assessment was based on the pupils’ recorded voices while reading the selected words. The results of the independent samples t-test indicated that using LDOCE significantly affected Iranian EFL learners' pronunciation accuracy with those in the experimental group outperforming their control group counterparts.

Keywords: LDOCE, EFL learners, pronunciation accuracy, CALL, MALL

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Authors: N. Maksimentseva

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The issue of public administration in subsoil use, renewal and protection is of high importance for Ukraine since it is strongly linked to energy security of the state as well as it shall facilitate the people of Ukraine to efficiently implement its propitiatory rights towards natural resources and redistribution of national wealth. As it is stipulated in the Article 11 of the Subsoil Code of Ukraine (the Code) the authorities that administer the industry are limited to central executive bodies and local governments. In particular, it is stipulated in the Code that the Ukraine’s Cabinet of Ministers carries out public administration in geological exploration, production and protection of subsoil. Other state bodies of public administration include central public authority responsible for state environmental protection policies; central public authority in charge of implementation of state geological exploration and efficient subsoil use policies; central authority in charge of state health and safety control policies. There are also public authorities in the Autonomous Republic of Crimea; local executive bodies and other state authorities and local self-government authorities in compliance with laws of Ukraine. This article is devoted to the analysis of the legal relations in the area of public administration of subsoil use, renewal and protection in Ukraine. The main approaches to study the essence of legal relations in the named area as well as its tasks, functions and methods are analyzed. It is concluded in this article that legal relationship in the field of public administration of subsoil use, renewal and protection is characterized by specifics of its task (development of natural resources).

Keywords: legal relations, public administration, subsoil code of Ukraine, subsoil use, renewal and protection

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Authors: Josine Beek, S. Agten, R. Del Pozo, B. Balis

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The objective of the present study was to compare the safety of intramuscular administration of Zuprevo® (tildipirosin, 40 mg/mL) with Draxxin® (tulathromycin, 100 mg/mL) in the treatment of swine respiratory disease at weaning age. The trial was carried out in two farrow-to-finish farms with 300 sows (farm A) and 500 sows (farm B) in a batch-production system. Farm A had no history of respiratory problems, whereas farm B had a history of respiratory outbreaks with increased mortality ( > 2%) in the nursery. Both farms were positive to Pasteurella multocida, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Haemophilus parasuis. From each farm, one batch of piglets was included (farm A: 644 piglets; farm B: 963 piglets). One day before weaning (day 0; 18-21 days of age), piglets were identified by an individual ear tag and randomly assigned to a treatment group. At day 0, Group 1 was treated with a single intramuscular injection with Zuprevo® (tildipirosin, 40 mg/mL; 1 mL/10 kg) and group 2 with Draxxin® (tulathromycin, 100 mg/mL; 1 mL/40 kg). For practical reasons, dosage of the product was adjusted according to three weight categories: < 4 kg, 4-6 kg and > 6 kg. Within each farm, piglets of both groups were comingled at weaning and subsequently managed and located in the same facilities and with identical environmental conditions. Our study involved the period from day 0 until 10 weeks of age. Safety of treatment was evaluated by 1) visual examination for signs of discomfort directly after treatment and after 15 min, 1 h and 24 h and 2) mortality rate within 24 h after treatment. Efficacy of treatment was evaluated based on mortality rate from day 0 until 10 weeks of age. Each piglet that died during the study period was necropsied by the herd veterinarian to determine the probable cause of death. Data were analyzed using binary logistic regression and differences were considered significant if p < 0.05. The pig was the experimental unit. In total, 848 piglets were treated with tildipirosin and 759 piglets with tulathromycin. In farm A, one piglet with retarded growth ( < 1 kg at 18 days of age) showed an adverse reaction after injection of tildipirosin: lateral recumbence and dullness for ± 30 sec. The piglet recovered after 1-2 min. This adverse reaction was probably due to overdosing (12 mg/kg). No adverse effect of treatment was observed in any other piglet. There was no mortality within 24 h after treatment. No significant difference was found in mortality rate between both groups from day 0 until 10 weeks of age. In farm A, overall mortality rate was 0.3% (2/644). In farm B, mortality rate was 0.2% (1/502) in group 1 (tildipirosin) and 0.9% (4/461) in group 2 (tulathromycin)(p=0.60). The necropsy of piglets that died during the study period revealed no macroscopic lesions of the respiratory tract. In conclusion, Zuprevo® (tildipirosin, 40 mg/mL) was shown to be a safe and efficacious alternative to Draxxin® (tulathromycin, 100 mg/mL) for the early treatment of swine respiratory disease at weaning age.

Keywords: antibiotic treatment, safety, swine respiratory disease, tildipirosin

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Authors: Sanan Raza, Tariq Abbas, Ahmad Yar Qamar, Muhammad Younus, Hamayun Khan, Mujahid Zafar

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Water Buffaloes contribute significantly in Asian agriculture. The objective of this study was to evaluate the efficacy of two synchronization protocols in enhancing pregnancy rate in 105 mixed parity buffaloes particularly in summer season. Buffaloes are seasonal breeders showing more fertility from October to January in subtropical environment of Pakistan. In current study 105 lactating buffaloes of mixed parity were used having normal estrous cycle, age ranging 5-9 years, weighing between 400-650 kg, BCS 4 ± 0.5 (1-5) and lactation varied from first to 5th. Experimental animals were divided into three groups based on corpus leteummorphometry. Morphometry of C.L was done using rectal population and ultrasonography. All animals were injected 25mg of PGi.m. (Cloprostenol). In Group-1 (n=35) hCG was administered at follicular size of 10mm having scanned after detection of heat. Similarly Group-2 (n=35) received 25 mg EB i.m (Estradiol Benzoate) after confirmation of follicular size of 10mm with ultrasound. Likewise, buffaloes of Group-3 (n=35) were administered normal saline respectively using as control. All buffaloes of three groups were inseminated after 12h of hCG, EB, and normal saline administration respectively. Pregnancy was assessed by ultrasound at 18th and 45th day post insemination. Pregnancy rates at 18th day were 38.2%, 34.5%, and 27.3% for G1, G2, and G3 respectively indicating that hCG and EB administered groups have no difference in results except control group having lower conception rate than both groups respectively. Similarly on 42nd day, these were 40.4%, 32.7% for G1 and G2 which are significantly higher than G3= 26.6 (control Group). Also, hCG and EB treated buffaloes have more probability of pregnancy than control group. Based on the findings of current study, it seems reasonable that the use of hCG and EB has been associated with improving pregnancy rates in non-breeding season of buffaloes.

Keywords: buffalo, hCG, EB, pregnancy rate, follicle, insemination

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Authors: Zine Kechrid

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This study was carried out to investigate the antioxidant effect of vitamin C on oxidative stress induced by dietary Zn-deficiency in albino diabetic rats. Thirty two males alloxan-diabetic rats divided into two groups of 16 individuals each; the first group was fed a zinc adequate diet (54 mg zinc/kg). The second group had given low zinc diet (1 mg zinc/kg). Then, half of each group was treated with vitamin C (1 g/l) in drinking water. After four weeks, animals were sacrificed and different parameters were determined. The findings showed that dietary deficiency zinc intake significantly increased serum glucose. Zn-deficiency was also led to an increase in oxidative stress, which was indicated by an increase of MDA level and glutathione-S-transferase activity. Meanwhile it was result in a decrease of reduced glutathione (GSH) content, glutathione peroxidase GSH-Px and catalase activities in liver. However, the administration of vitamin C restored all the previous parameters approximately to their normal values. In conclusion, vitamin C probably played a key role strong as antioxidant factor against oxidative stress provoked by dietary zinc inadequate. Therefore, it might be contributed in reduction diabetes complications.

Keywords: vitamin C, oxidative stress, zinc, experimental diabetes, rats

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Authors: Cangir Uyarlar, Eyup Eren Gultepe, Mustafa Kabu, Hacı Ahmet Celik

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This study aimed to evaluate the effects of orally Immunoglobulin (Ig) Y treatments to calves were fed with colostrum having insufficient antibodies before first suckling. A total of 28 Holstein calves were fed assigned into control and treatment groups. The calves were fed fresh colostrum from their respective mother for the first 4 days. The treatment group calves were orally administered IgLock (10 g/d/calf) immediately before the first colostrum feeding and IgLock was administered just one time in treatment group calves. Then, the calves were offered normal milk until weaning. After weaning, all calves kept same paddock and were fed same ration. Diarrhea and respiratoric diseases were recorded for one year. Blood was collected from all calves in the study on birth day (0 day) before vaccination and IgLock administration, then, collected for the following 2 days in all groups. Albumin (ALB), Total Protein (TP), Aspartate Aminotransferase (AST), Alanine Aminotrasferase (ALT), Gamma-Glutamyl Transferase (GGT), Serum Amyloid A (SAA), Haptoglobin (HPT) and Ig G analyses were performed on all samples. Although serum ALB, ALT, GGT and Ig G levels were not shown a time dependent-change within control group; serum TP, AST, HPT and SAA levels were significantly changed by the time within mentioned group. Serum TP level was steady at first 2 days, then, it was increased significantly at 3rd day. Also, serum AST level was significantly increased at 2nd day, then it was descended to first day levels again at 3rd day. Although serum HPT levels were shown a significant gradually decreasing within control group, serum SAA levels were decreased rapidly after first day and there were no significance differences between 2nd and 3rd day in SAA levels. Serum ALB, ALT, HPT and SAA levels were not shown a time dependent-change within treatmet group. After first day Serum TP, GGT, AST and Ig G levels were shown an significant increasing at 2nd day. Serum TP, GGT and Ig G levels were higher as compared to 1st day within treatment group at 3rd day. But, serum AST level was less significantly 3rd day as compared to 2nd day values. The total numbers of calves suffered from diarrhea were significantly less in treatment group as compared to control group (p < 0,05). The pneumonia reappear ratio in calves suffered the diseases is 33,3% in control group and 11,11% in treatment group. Total cost of diseases and additives was 2339,36 $ for control and 1276,4 $ for treatment. As a conclusion, the immunity enhancers like IgLock are important and cost-effective to boost up immunity status in the early age which would be having positive effects on calves were received colostrum included insufficient antibodies.

Keywords: dairy calves, Ig Y, pneumonia, scours

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Authors: Sukanya Sripho

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The purpose of this research was to study the role of local administration management to promote culture based on philosophy of sufficiency economy to many communities in Thailand. The philosophy was given to the Thai people by their King and become one of the important policies from the Thai government. A total of 375 local people in main district, Amnadcharoen province were selected by random sampling. A questionnaire was used as the tool for collecting data. Descriptive statistics in this research included percentage, mean, and multiple regression analysis. The findings revealed that the role of facilitator was utilized the most from the management in order to promote culture based on philosophy of sufficiency economy to many communities in Thailand.

Keywords: administration, management, philosophy of sufficiency economy, facilitator

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Authors: Suparmi, Israhnanto Isradji, Dina Fatmawati, Iwang Yusuf

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Kepel (Stelechocarpus burahol) is one of the traditional plants originating from Indonesia that can be used to prevent pregnancy, launched urine and kidney inflammation. Kepel pulp has compounds alkaloid, triterpenoid, tannin, saponin, and flavonoid, when used will give the hormonal and cytotoxic effect. This study was aimed at evaluating ethanol extract of kepel in vivo for anti-implantation activities. In this experimental study with post test only control group design, 20 female mice were randomly divided into 4 groups. It was divided into the control, the 0,65 mg dose, 1,3 mg dose, and 3,6 mg dose of kepel pulp extract group. The extract soluted in DMSO’s solution and was given 1 ml per mice. The extract was given 10 days before copulation until 18 days of pregnancy. Then, the number of implantation, presence of fetus, and embrio resorbtion were recorded and used to calculate the percentage anti-implantation effect. The results were tested by One-way ANOVA. The mean number of implantation in group control, 0,65 mg;1,3 mg; and 2,6 mg were 5,60±1,14; 6,20± 1,64; 7,60±1,51; 8,00± 1,58, respectively. One way Annova test showed that there is no significant difference in the number of implantation between the group (p > 0,05). The administration of kepel pulp ethanol extract had no effect on the percentage anti-implantation effect and the number of and embrio resorbtion.

Keywords: antiimplantation, fetus, Stelechocarpus burahol, flavonoid

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Authors: Ola Abdel-Tawab Hussein

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Background: Boron is a naturally occurring agent and an essential trace element of human, animals and higher plants. It is released in the form of boric acid (BA) that is water soluble and biolologically available. Its largest uses are in glass, detergents, agriculture, leather tanning industries, cosmetics, photographic materials, soaps and cleaners. Human consume daily few milligrams in the water, fruits and vegetables. High doses of boron had been recorded to be developmental and reproductive toxin in animals(Only few studies on human had investigated the health effects associated with exposure to boron. Vitamin C is a major water soluble non-enzymatic antioxidant, acts to overcome the oxidative stress. Aim of the work: However , the liver is exposed to toxic substances that are absorbed, degraded or conjugated there were little information exists about the effects of boron that it would specifically have in the liver tissue of experimental rats. So the present work aimed to study the effects of long-term boron ingestion on histological structural of the liver of adult male albino rats and to evaluate the protective role of vitamin C against induced changes. Material and Methods: 30 adult male albino rats were divided into 3 equal groups; Group I: control, Group II: recieved drinking water containing 55x10-6 gm boron/liter for 90 days and Group III: recieved vitamin C (200mg/Kg.B.W) orally concomitant with boron for the same period. liver specimens were processed for light and electron microscopic(TEM) study. Results: Examination of the liver sections of group II revealed foci of severe dilatation and congestion of central and portal veins with mononuclear cellular infiltration and hepatocellular vacuolation. Increased collagen deposition specially around the portal areas. Marked electrolucent areas in the cytoplasm, heterochromatic nuclei and destroyed organelles of the hepatocytes. Apoptotic cells were observed and decreased lipid content of ito cells. In Group III the co administration of vitamin C improved most of the structural changes of the hepatocytes, Ito cells, increased binucleated cells and decreased collagen fibers deposition. Conclusion: Thus, the long term exposure to boron, induced histological changes on the structure of liver. The co administration of vitamin C improved most of these structural changes.

Keywords: boron, liver, vitamin C, rats

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Authors: Mahmut Sozmen, Alparslan Kadir Devrim, Yonca Betil Kabak, Tuba Devrim

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Acute myocardial infarction is the leading cause of deaths in the worldwide. Mature cardiomyocytes do not have the ability to regenerate instead fibrous tissue proliferate and granulation tissue to fill out. Periostin is an extracellular matrix protein from fasciclin family and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The main objective of this project is to investigate the effects of the recombinant murine periostin peptide administration for the cardiomyocyte regeneration in a rat model of acute myocardial infarction. The experiment was performed on 84 male rats (6 months old) in 4 group each contains 21 rats. Saline applied subcutaneously (1 ml/kg) two times with 24 hours intervals to the rats in control group (Group 1). Recombinant periostin peptide (1 μg/kg) dissolved in saline applied intraperitoneally in group 2 on 1, 3, 7, 14 and 21. days on same dates in group 4. Isoproterenol dissolved in saline applied intraperitoneally (85mg/kg/day) two times with 24 hours intervals to the groups 3 and 4. Rats in group 4 further received recombinant periostin peptide (1 μg/kg) dissolved in saline intraperitoneally starting one day after the final isoproterenol administration on days 1, 3, 7, 14 and 21. Following the final application of periostin rats continued to feed routinely with pelleted chow and water ad libitum for further seven days. At the end of 7th day rats sacrificed, blood and heart tissue samples collected for the immunohistochemical and biochemical analysis. Angiogenesis in response to tissue damage, is a highly dynamic process regulated by signals from the surrounding extracellular matrix and blood serum. In this project, VEGF, ANGPT, bFGF, TGFβ are the key factors that contribute to cardiomyocyte regeneration were investigated. Additionally, the relationship between mitosis and apoptosis (Bcl-2, Bax, PCNA, Ki-67, Phopho-Histone H3), cell cycle activators and inhibitors (Cyclin D1, D2, A2, Cdc2), the origin of regenerating cells (cKit and CD45) were examined. Present results revealed that periostin stimulated cardiomyocye cell-cycle re-entry in both normal and MCA damaged cardiomyocytes and increased angiogenesis. Thus, periostin contributes to cardiomyocyte regeneration during the healing period following myocardial infarction which provides a better understanding of its role of this mechanism, improving recovery rates and it is expected to contribute the lack of literature on this subject. Acknowledgement: This project was financially supported by Turkish Scientific Research Council- Agriculture, Forestry and Veterinary Research Support Group (TUBİTAK-TOVAG; Project No: 114O734), Ankara, TURKEY.

Keywords: cardiotoxicity, immunohistochemistry, isoproterenol, periostin

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Authors: A. ElZawam, D. McLean, A. Tibary

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In alpaca, age at puberty is variable and the factors regulating the pattern of puberty and sexual maturation are a subject of controversy. Plasma testosterone level is often used as an indicator of sexual maturity. Our hypothesis is that hCG treatment will cause an increase in testosterone level that is correlated with animal age. The specific aim was to investigate the testicular tissue response to a single hCG injection by monitoring the serum testosterone concentration. Eighty four (n=84) males ranging in age from 6 to 60 months were used. Alpacas were grouped based on their ages into 15 groups. Each group had three to five male animals. Blood samples were collected from the jugular vein before treatment with hCG and 2 hours after intravenous administration of 3000 IU of hCG (Chorulon®). The serum was harvested and stored at -20ºC until the analysis. The effect of age on basal testosterone level and response to hCG treatment was evaluated by Analysis of Variance. As a result, basal serum testosterone concentrations were very low (<0.1ng/ml) until 9 months of age. Although basal serum testosterone concentrations increased steadily with age there was a significant variation amongst males within the same age group. Administration of 3000 IU of hCG, resulted in an average increase of 50% (P<0.05) in serum testosterone concentration after 2 hours. The percentage increase in serum testosterone in response to hCG stimulation varied from 51 to 81%. There was no correlation between the degree of response and age. However, the response to hCG injection presented two modes of increase depending on the age of animals. The first mode occurred at ages 9 to 14 months and the second mode was observed between 22 and 36 months. In conclusion, our results suggest that testicular growth and sensitivity to LH stimulation may be bimodal in the male alpaca with a rapid increase in growth and sensitivity between 9 and 14 months of age and a second phase of increased responsiveness after 21 months of ages.

Keywords: alpaca, testosterone, hCG, animal science

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: Iñaki Milton-Laskibar, Leixuri Aguirre, Maria P. Portillo

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Introduction: Energy restriction is an effective approach in preventing liver steatosis. However, due to social and economic reasons among others, compliance with this treatment protocol is often very poor, especially in the long term. Resveratrol, a natural polyphenolic compound that belongs to stilbene group, has been widely reported to imitate the effects of energy restriction. Objective: To analyze the effects of resveratrol under normoenergetic feeding conditions and under a mild energy restriction on liver fat accumulation and hepatic fatty acid oxidation. Methods: 36 male six-week-old rats were fed a high-fat high-sucrose diet for 6 weeks in order to induce steatosis. Then, rats were divided into four groups and fed a standard diet for 6 additional weeks: control group (C), resveratrol group (RSV, resveratrol 30 mg/kg/d), restricted group (R, 15 % energy restriction) and combined group (RR, 15 % energy restriction and resveratrol 30 mg/kg/d). Liver triacylglycerols (TG) and total cholesterol contents were measured by using commercial kits. Carnitine palmitoyl transferase 1a (CPT 1a) and citrate synthase (CS) activities were measured spectrophotometrically. TFAM (mitochondrial transcription factor A) and peroxisome proliferator-activator receptor alpha (PPARα) protein contents, as well as the ratio acetylated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/Total PGC1α were analyzed by Western blot. Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: No differences were observed among the four groups regarding liver weight and cholesterol content, but the three treated groups showed reduced TG when compared to the control group, being the restricted groups the ones showing the lowest values (with no differences between them). Higher CPT 1a and CS activities were observed in the groups supplemented with resveratrol (RSV and RR), with no difference between them. The acetylated PGC1α /total PGC1α ratio was lower in the treated groups (RSV, R and RR) than in the control group, with no differences among them. As far as TFAM protein expression is concerned, only the RR group reached a higher value. Finally, no changes were observed in PPARα protein expression. Conclusions: Resveratrol administration is an effective intervention for liver triacylglycerol content reduction, but a mild energy restriction is even more effective. The mechanisms of action of these two strategies are different. Thus resveratrol, but not energy restriction, seems to act by increasing fatty acid oxidation, although mitochondriogenesis seems not to be induced. When both treatments (resveratrol administration and a mild energy restriction) were combined, no additive or synergic effects were appreciated. Acknowledgements: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: energy restriction, fat, liver, oxidation, resveratrol

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Authors: Chia-Ching Tsai

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The study examined the control illusion of conditioned superstition by using Taiwanese subjects. The study had a three-group experimental design, that is, conditioning group and a control group, and the conditioning group was further separated into superstitious and unsuperstitious groups. The results showed that conditioned superstition can significantly influence the control illusion. Further analysis showed that the control illusion in the superstitious conditioning group was significantly greater than in the control group or in the unsuperstitious conditioning group. Besides, there was no significant difference between the control group and the unsuperstitious conditioning group.

Keywords: Control illusion, Conditioned superstition, experimental design

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Authors: Lina Liang, Kai Xu, Jing Zhang

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Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement is discussed as a potential therapy for AMD. Besides intravitreal injection and subretinal injection, intravenous administration has been explored as an alternative route. This study is to observe the effect of BSYJ, a traditional Chinese medicine on the homing and differentiation of mesenchymal stem cells transplanted via tail vein injection in an age-related macular degeneration mouse model. Methods: Four-week-old C57BL/6J mice were injected with 40 mg/kg NaIO₃ to induce age-related macular degeneration model. At the second day after NaIO₃ injection, 1×10⁷ GFP labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs) were transplanted via tali vein injection into the experimental mice. Then the mice were randomly divided into two groups, gavaged with either BSYJ solution (BSYJ group, n=12) or distilled water (DW group, n=12). 12 age-matched healthy C57BL/6J mice were fed regularly as normal control. At day 7, day 14, and day 28 after treatment, retina flat mounting was used to detect the homing of mesenchymal stem cells at the retina. Double-labeling immunofluorescence was used to determine the differentiation of mesenchymal stem cells. Results: At 7, 14, 28 days after treatment, the numbers of GFP-MSCs detected by retina flatmount were 10.2 ± 2.5, 14.5 ± 3.4 and 18.7 ± 5.8, respectively in the distilled water group, while 15.7 ± 3.8, 32.3 ± 3.5 and 77.3 ± 6.4 in BSYJ group, the differences between the two groups were significant (p < 0.05). At 28 days after treatment, it was shown by double staining immunofluorescence that there were more GFP positive cells in the retina of BSYJ group than that of the DW group, but none of the cells expressed RPE specific genes such as RPE65 and CRALBP, or photoreceptor genes such as recoverin and rhodopsin either in BSYJ group or DW group. However, GFAP positive cells were found among the cells labeled with GFP, and the double labeling cells were much more in the BSYJ group than the distilled water group. Conclusion: BSYJ could promote homing of mesenchymal stem cells at the retina of age-related macular degeneration model mice induced by NaIO₃, and the differentiation towards to glial cells. Acknowledgement: National Natural Foundation of China (No: 81473736, 81674033,81973912).

Keywords: BSYJ, differentiation, homing, mesenchymal stem cells

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Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

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Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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