Search results for: half dose thrombolysis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2715

Search results for: half dose thrombolysis

2115 Pyrazolylpyrazolines: Design, Synthesis and Biological Evaluation as Dual Acting Antimalarial-Antileishmanial Agents

Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

Abstract:

Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

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2114 Study of the Protective Effects of Summer Savory against Multiple Organ Damage Induced by Lead Acetate in Rats

Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

Abstract:

Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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2113 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

Abstract:

The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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2112 Design and Implementation of Control System in Underwater Glider of Ganeshblue

Authors: Imam Taufiqurrahman, Anugrah Adiwilaga, Egi Hidayat, Bambang Riyanto Trilaksono

Abstract:

Autonomous Underwater Vehicle glider is one of the renewal of underwater vehicles. This vehicle is one of the autonomous underwater vehicles that are being developed in Indonesia. Glide ability is obtained by controlling the buoyancy and attitude of the vehicle using the movers within the vehicle. The glider motion mechanism is expected to provide energy resistance from autonomous underwater vehicles so as to increase the cruising range of rides while performing missions. The control system on the vehicle consists of three parts: controlling the attitude of the pitch, the buoyancy engine controller and the yaw controller. The buoyancy and pitch controls on the vehicle are sequentially referring to the finite state machine with pitch angle and depth of diving inputs to obtain a gliding cycle. While the yaw control is done through the rudder for the needs of the guide system. This research is focused on design and implementation of control system of Autonomous Underwater Vehicle glider based on PID anti-windup. The control system is implemented on an ARM TS-7250-V2 device along with a mathematical model of the vehicle in MATLAB using the hardware-in-the-loop simulation (HILS) method. The TS-7250-V2 is chosen because it complies industry standards, has high computing capability, minimal power consumption. The results show that the control system in HILS process can form glide cycle with depth and angle of operation as desired. In the implementation using half control and full control mode, from the experiment can be concluded in full control mode more precision when tracking the reference. While half control mode is considered more efficient in carrying out the mission.

Keywords: control system, PID, underwater glider, marine robotics

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2111 Predictors for Success in Methadone Maintenance Treatment Clinic: 24 Years of Experience

Authors: Einat E. Peles, Shaul Schreiber, Miriam Adelson

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Background: Since established more than 50 years ago, methadone maintenance treatment (MMT) is the most effective treatment for opioid addiction, a chronic relapsing brain disorder that became an epidemic in western societies. Treatment includes daily individual optimal medication methadone dose (a long acting mu opioid receptor full agonist), accompanied with psychosocial therapy. It is well established that the longer retention in treatment the better outcome and survival occur. It reduces the likelihood to infectious diseases and overdose death that associated with drug injecting, enhanced social rehabilitation and eliminate criminal activity, and lead to healthy productive life. Aim: To evaluate predictors for long term retention in treatment we analyzed our prospective follow up of a major MMT clinic affiliated to a big tertiary medical center. Population Methods: Between June 25, 1993, and June 24, 2016, all 889 patients ( ≥ 18y) who ever admitted to the clinic were prospectively followed-up until May 2017. Duration in treatment from the first admission until the patient quit treatment or until the end of follow-up (24 years) was taken for calculating cumulative retention in treatment using survival analyses (Kaplan Meier) with log-rank and Cox regression for multivariate analyses. Results: Of the 889 patients, 25.2% were females who admitted to treatment at younger age (35.0 ± 7.9 vs. 40.6 ± 9.8, p < .0005), but started opioid usage at same age (22.3 ± 6.9). In addition to opioid use, on admission to MMT 58.5% had positive urine for benzodiazepines, 25% to cocaine, 12.4% to cannabis and 6.9% to amphetamines. Hepatitis C antibody tested positive in 55%, and HIV in 7.8% of the patients and 40%. Of all patients, 75.7% stayed at least one year in treatment, and of them, 67.7% stopped opioid usage (based on urine tests), and a net reduction observed in all other substance abuse (proportion of those who stopped minus proportion of those who have started). Long term retention up to 24 years was 8.0 years (95% Confidence Interval (CI) 7.4-8.6). Predictors for longer retention in treatment (Cox regression) were being older on admission ( ≥ 30y) Odds Ratio (OR) =1.4 (CI 1.1-1.8), not abusing opioids after one year OR=1.8 (CI 1.5-2.1), not abusing benzodiazepine after one year OR=1.7 (CI 1.4-2.1) and treating with methadone dose ≥ 100mg/day OR =1.8 (CI 1.5-2.3). Conclusions: Treating and following patients over 24 years indicate success of two main outcomes, high rate of retention after one year (75.7%) and high proportion of opiate abuse cessation (67.7%). As expected, longer cumulative retention was associated with patients treated with high adequate methadone dose that successfully result in opioid cessation. Based on these findings, in order to reduce morbidity and mortality, we find the establishment of more MMT clinics within a general hospital, a most urgent necessity.

Keywords: methadone maintenance treatment, epidemic, opioids, retention

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2110 Opuntia ficus-indica var. Saboten Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in 3T3-L1 Adipocytes

Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

Abstract:

The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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2109 A Retrospective Analysis of the Use of Vancomycin by Continous Infusion in the Critical Care Setting, Edinburgh

Authors: Sonia Nemakallu, Pota Kalima

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Introduction: Vancomycin is a glycopeptide antibiotic, commonly used to treat gram-positive bacteraemia. It has been increasingly used in the critical care setting due to an increased awareness of resistant gram positive organisms. In Edinburgh both tertiary hospitals, The Western General Hospital and The Royal Infirmary Of Edinburgh, commonly use Vancomycin for a variety of infections. Administration of Vancomyicn in these hospitals is by continuous infusion as it is thought to maintain serum concentrations easier and is a simpler monitoring system. Purpose: The aim of the study was to evaluate the efficacy and reliability in which Vancomycin is used. Material and Methods: A retrospective study, over a 6-month period from January 2014 to June 2014. 91 admissions were included, all received Vancomycin by continuous infusion during their critical care stay. Results: The number one use for Vancomycin in critical care settings was in the treatment of ventilator or hospital-acquired pneumonia. Only 3% of population had MRSA. 49% of admissions were not therapeutic on day 1 post loading dose. Of those that were therapeutic on day 1 post loading dose, 39% of admissions showed no organisms in any cultures taken, 42% had organisms sensitive to Vancomycin and 19% had only organisms resistant to Vancomycin. Those that were not therapeutic on day 1 showed similar organism sensitivities. 15% of admissions had Vancomycin levels above 25 (levels should be maintained between 15-25). An increase in creatinine was proportionally seen with an increase in Vancomycin levels. Conclusion: Within Edinburgh Vancomycin is being overused in the critical care setting with only 3% of the population having highly resistant organisms. Continuous infusion have not ruled out the complexity of maintaining therapeutic levels, with a large proportion of patients not being therapeutic on day 1. Further research is also required into the nephrotoxic effects of using higher doses of Vancomycin.

Keywords: Vancomycin, continuous infusion, multi resistant organisms, sepsis, renal toxicity

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2108 Assessing Image Quality in Mobile Radiography: A Phantom-Based Evaluation of a New Lightweight Mobile X-Ray Equipment

Authors: May Bazzi, Shafik Tokmaj, Younes Saberi, Mats Geijer, Tony Jurkiewicz, Patrik Sund, Anna Bjällmark

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Mobile radiography, employing portable X-ray equipment, has become a routine procedure within hospital settings, with chest X-rays in intensive care units standing out as the most prevalent mobile X-ray examinations. This approach is not limited to hospitals alone, as it extends its benefits to imaging patients in various settings, particularly those too frail to be transported, such as elderly care residents in nursing homes. Moreover, the utility of mobile X-ray isn't confined solely to traditional healthcare recipients; it has proven to be a valuable resource for vulnerable populations, including the homeless, drug users, asylum seekers, and patients with multiple co-morbidities. Mobile X-rays reduce patient stress, minimize costly hospitalizations, and offer cost-effective imaging. While studies confirm its reliability, further research is needed, especially regarding image quality. Recent advancements in lightweight equipment with enhanced battery and detector technology provide the potential for nearly handheld radiography. The main aim of this study was to evaluate a new lightweight mobile X-ray system with two different detectors and compare the image quality with a modern stationary system. Methods: A total of 74 images of the chest (chest anterior-posterior (AP) views and chest lateral views) and pelvic/hip region (AP pelvis views, hip AP views, and hip cross-table lateral views) were acquired on a whole-body phantom (Kyotokagaku, Japan), utilizing varying image parameters. These images were obtained using a stationary system - 18 images (Mediel, Sweden), a mobile X-ray system with a second-generation detector - 28 images (FDR D-EVO II; Fujifilm, Japan) and a mobile X-ray system with a third-generation detector - 28 images (FDR D-EVO III; Fujifilm, Japan). Image quality was assessed by visual grading analysis (VGA), which is a method to measure image quality by assessing the visibility and accurate reproduction of anatomical structures within the images. A total of 33 image criteria were used in the analysis. A panel of two experienced radiologists, two experienced radiographers, and two final-term radiographer students evaluated the image quality on a 5-grade ordinal scale using the software Viewdex 3.0 (Viewer for Digital Evaluation of X-ray images, Sweden). Data were analyzed using visual grading characteristics analysis. The dose was measured by the dose-area product (DAP) reported by the respective systems. Results: The mobile X-ray equipment (both detectors) showed significantly better image quality than the stationary equipment for the pelvis, hip AP and hip cross-table lateral images with AUCVGA-values ranging from 0.64-0.92, while chest images showed mixed results. The number of images rated as having sufficient quality for diagnostic use was significantly higher for mobile X-ray generation 2 and 3 compared with the stationary X-ray system. The DAP values were higher for the stationary compared to the mobile system. Conclusions: The new lightweight radiographic equipment had an image quality at least as good as a fixed system at a lower radiation dose. Future studies should focus on clinical images and consider radiographers' viewpoints for a comprehensive assessment.

Keywords: mobile x-ray, visual grading analysis, radiographer, radiation dose

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2107 Kawasaki Disease in a Two Months Kuwaiti Girl: A Case Report ‎and Literature Review.‎

Authors: Hanan Bin Nakhi, Asaad M. Albadrawi, Maged Al Shahat, ‎Entesar Mandani

Abstract:

Background:‎ Kawasaki disease (KD) is one of the most common vasculitis of childhood. ‎It is considered the leading cause of acquired heart disease in children. The ‎peak age of occurrence is 6 to 24 months, with 80% of affected children being ‎less than 5 years old. There are only a few reports of KD in infants younger ‎than 6 months. Infants had a higher incidence of atypical KD and of coronary ‎artery complications. This case report from Kuwait will reinforce considering ‎atypical KD in case of sepsis like condition with negative cultures and ‎unresponding to systemic antibiotics. Early diagnosis allows early treatment ‎with intravenous immune globulin (IVIG) and so decreases the incidence of ‎cardiac aneurysm.‎ Case Report:‎ A 2 month old female infant, product of full term normal delivery to ‎consanguineous parents, presented with fever and poor feeding. She was ‎admitted and treated as urinary tract infection as her urine routine revealed ‎pyurea. The baby continued to have persistent fever and hypoactivity inspite ‎of using intravenous antibiotics. Latter, she developed non purulent ‎conjunctivitis, skin mottling, oedema of the face / lower limb and was treated ‎in intensive care unit as a case of septic shock. In spite of her partial general ‎improvement, she continued to look unwell, hypoactive and had persistent ‎fever. Septic work up, metabolic, and immunologic screen were negative. KD ‎was suspected when the baby developed polymorphic erythematous rash and ‎noticed to have peeling of skin at perianal area and periangular area of the ‎fingers of the hand and feet. IVIG was given in dose of 2 gm/kg/day in single ‎dose and aspirin 100 mg/kg/day in four divided doses. The girl showed marked ‎clinical improvement. The fever subsided dramatically and the level acute ‎phase reactant markedly decreased but the platelets count increased to ‎‎1600000/mm3. Echo cardiography showed mild dilatation of mid right ‎coronary artery. Aspirin was continued in a dose of 5 mg/kg/d till repeating ‎cardiac echo. ‎Conclusion:‎ A high index of suspicion of KD must be maintained in young infants with ‎prolonged unexplained fever. Accepted criteria should be less restrictive to ‎allow early diagnosis of a typical KD in infants less than 6 months of age. ‎Timely appropriate treatment with IVIG is essential to avoid severe coronary ‎sequels.‎

Keywords: Kawasaki disease, atypical Kawasaki disease, infantile Kawasaki disease, hypo activity‎ ‎

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2106 Anti-Obesity Effects of Pteryxin in Peucedanum japonicum Thunb Leaves through Different Pathways of Adipogenesis In-Vitro

Authors: Ruwani N. Nugara, Masashi Inafuku, Kensaku Takara, Hironori Iwasaki, Hirosuke Oku

Abstract:

Pteryxin from the partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as the active compound related to anti-obesity. Thus, in this study we investigated the mechanisms related to anti-obesity activity in-vitro. The HP was fractionated, and effect on the triglyceride (TG) content was evaluated in 3T3-L1 and HepG2 cells. Comprehensive spectroscopic analyses were used to identify the structure of the active compound. The dose dependent effect of active constituent on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis and lipogenesis (20 μg/mL) were examined in-vitro. Furthermore, higher dosage of pteryxin (50μg/mL) was tested against 20μg/mL in 3T3-L1 adipocytes. The mRNA were subjected to SOLiD next generation sequencer and the obtained data were analyzed by Ingenuity Pathway Analysis (IPA). The active constituent was identified as pteryxin, a known compound in PJT. However, its biological activities against obesity have not been reported previously. Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes and HepG2 hepatocytes (P < 0.05). Sterol regulatory element-binding protein-1 (SREBP1 c), Fatty acid synthase (FASN), and acetyl-CoA carboxylase-1 (ACC1) were downregulated in pteryxin-treated adipocytes (by 18.0, 36.1 and 38.2%; P < 0.05, respectively) and hepatocytes (by 72.3, 62.9 and 38.8%, respectively; P < 0.05) indicating its suppressive effects on fatty acid synthesis. The hormone-sensitive lipase (HSL), a lipid catabolising gene was upregulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes suggesting improved lipolysis. Concordantly, the adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was downregulated (by 42.8%; P < 0.05), further accelerating the lipolytic activity. The upregulated trend of uncoupling protein 2 (UCP2; by 77.5%; P < 0.05) reflected the improved energy expenditure due to pteryxin. The 50μg/mL dosage of pteryxin completely suppressed PPARγ, MEST, SREBP 1C, HSL, Adiponectin, Fatty Acid Binding Protein (FABP) 4, and UCP’s in 3T3-L1 adipocytes. The IPA suggested that pteryxin at 20μg/mL and 50μg/mL suppress obesity in two different pathways, whereas the WNT signaling pathway play a key role in the higher dose of pteryxin in preadipocyte stage. Pteryxin in PJT play the key role in regulating lipid metabolism related gene network and improving energy production in vitro. Thus, the results suggests pteryxin as a new natural compound to be used as an anti-obesity drug in pharmaceutical industry.

Keywords: obesity, peucedanum japonicum thunb, pteryxin, food science

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2105 The Use of the Mediated Learning Experience in Response of Special Needs Education

Authors: Maria Luisa Boninelli

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This study wants to explore the effects of a mediated intervention program in a primary school. The participants where 120 students aged 8-9, half of them Italian and half immigrants of first or second generation. The activities consisted on the cognitive enhancement of the participants through Feuerstein’s Instrumental Enrichment, (IE) and on an activity centred on body awareness and mediated learning experience. Given that there are limited studied on learners in remedial schools, the current study intented to hypothesized that participants exposed to mediation would yiel a significant improvement in cognitive functioning. Hypothesis One proposed that, following the intervention, improved Q1vata scores of the participants would occur in each of the groups. Hypothesis two postulated that participants within the Mediated Learning Experience would perform significantly better than those group of control. For the intervention a group of 60 participants constituted a group of Mediation sample and were exposed to Mediated Learning Experience through Enrichment Programm. Similiary the other 60 were control group. Both the groups have students with special needs and were exposed to the same learning goals. A pre-experimental research design, in particular a one-group pretest-posttest approach was adopted. All the participants in this study underwent pretest and post test phases whereby they completed measures according to the standard instructions. During the pretest phase, all the participants were simultaneously exposed to Q1vata test for logical and linguistic evaluation skill. During the mediation intervention, significant improvement was demonstrated with the group of mediation. This supports Feuerstein's Theory that initial poor performance was a result of a lack of mediated learning experience rather than inherent difference or deficiencies. Furthermore the use of an appropriate mediated learning enabled the participants to function adequately.

Keywords: cognitive structural modifiability, learning to learn, mediated learning experience, Reuven Feuerstein, special needs

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2104 Management of Insect Pests Using Baculovirus Based Biopesticides in India

Authors: Mudasir Gani, Rakesh Kumar Gupta, Kamlesh Bali, Abdul Rouf Wani

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The gypsy moth (Lymantria obfuscata) and tent caterpillar (Malacosoma indicum) are serious pests that attack a wide range of fruit and forest trees in Jammu & Kashmir range of North-Western Himalayas in India. Investigations were carried out to isolate and bioprospect naturally occurring nucleopolyhedroviruses (NPVs) as potent biopesticides against these pests. The biological and molecular characterization of NPV isolates from different ecosystems was conducted, and the polh, lef-8 and lef-9 genes were sequenced and subjected to phylogenetic analysis. The L. obfuscata NPV was more closely related to the L. dispar NPV, whereas M. indicum NPV was more closely related to the M. californicum NPV in the NCBI taxonomy database. Among different isolates, Bhaderwah isolates exhibited highest virus activity (LD₅₀ = 250 POBs/larvae) and speed of kill (ST₅₀ = 6.80 days) against L. obfuscata whereas Mahor isolates proved most virulent against M. indicum, with lowest LD₅₀ (257 POBs/larva) and ST₅₀ (6.80 days). The in vivo mass production for highest productivity and quality revealed that the optimum yield was obtained when 3rd instar larvae were inoculated with a viral dose of 1.44 × 105 POBs/larva and allowed to incubate for nine days for L. obfuscata. However, for M. indicum larvae, a viral dose of 2.88 × 10⁶ POBs/larva and incubation period of 10 days were found optimum. It was found that harvesting of moribund larvae yields good quality NPV. The field application of L. obfuscata NPV and M. indicum NPV against the respective host populations on apple and willow with the pre-standardized dosage of 1 × 10¹² POBs/acre reduced the larval population density up to 25-63%.

Keywords: baculoviruses, biopesticides, Lymantria obfuscata, Malacosoma indicum

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2103 Research of Actuators of Common Rail Injection Systems with the Use of LabVIEW on a Specially Designed Test Bench

Authors: G. Baranski, A. Majczak, M. Wendeker

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Currently, the most commonly used solution to provide fuel to the diesel engines is the Common Rail system. Compared to previous designs, as a due to relatively simple construction and electronic control systems, these systems allow achieving favourable engine operation parameters with particular emphasis on low emission of toxic compounds into the atmosphere. In this system, the amount of injected fuel dose is strictly dependent on the course of parameters of the electrical impulse sent by the power amplifier power supply system injector from the engine controller. The article presents the construction of a laboratory test bench to examine the course of the injection process and the expense in storage injection systems. The test bench enables testing of injection systems with electromagnetically controlled injectors with the use of scientific engineering tools. The developed system is based on LabView software and CompactRIO family controller using FPGA systems and a real time microcontroller. The results of experimental research on electromagnetic injectors of common rail system, controlled by a dedicated National Instruments card, confirm the effectiveness of the presented approach. The results of the research described in the article present the influence of basic parameters of the electric impulse opening the electromagnetic injector on the value of the injected fuel dose. Acknowledgement: This work has been realized in the cooperation with The Construction Office of WSK ‘PZL-KALISZ’ S.A.’ and is part of Grant Agreement No. POIR.01.02.00-00-0002/15 financed by the Polish National Centre for Research and Development.

Keywords: fuel injector, combustion engine, fuel pressure, compression ignition engine, power supply system, controller, LabVIEW

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2102 Involvement of BCRP/ABCG2 in Protective Mechanisms of Resveratrol against Methotrexate-Induced Renal Damage in Rats

Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

Abstract:

Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

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2101 Hyparrhenia hirta: A Potential Protective Agent against DNA Damage and Liver Toxicity of Sodium Nitrate in Adult Rats

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

Abstract:

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

Procedia PDF Downloads 521
2100 Unhealthy Food Consumption Behavior in Suan Sunandha Rajabhat Universities

Authors: Narumon Piaseu

Abstract:

This survey research was aimed to describe and compare consumption behavior of health risk food among students in Suan Sunandha Rajabhat University. Sample included 400 undergraduate students enrolled in the first semester of 2008 academic year. Data were collected by using self reported questionnaire developed by the researcher. Data were then analyzed by descriptive statistics including frequency, percentage, mean, standard deviation, and inferential statistics including independent t-test, and Oneway ANOVA. Results revealed that most of the sample were women (67%), enrolled in social related programs (74%). Approximately half of them (45.5%) stayed in dormitory. The mean of monthly income was 5,164 Baht and daily food expenditure was 114.55 Baht. Majority of them (83%) had ready-to-eat food. A major factor influencing their food selection was their parents (61%). A main reason for their food selection was food that looks good (70.75%). Almost half of them (46.25%) had heavy exercise less than 3 times per week. Regarding knowledge on health risk food, 43.5% of the sample had good knowledge. The followings were moderate (41%) and poor (41%). Most of the sample (60.75%) had consumption behavior at low risk. The following was at moderate risk (37.25%). Only 2% were at high risk. Among the sample, consumption behavior of health risk food were significantly different in years of study (F = 3.168, p = .024), daily food expenditure (F = 8.950, p <.001), and knowledge on health risk food (F = 37.856, p <.001), while no significant difference in consumption behavior of health risk food was found in those with a difference in gender, program of study, living place, and monthly income. Results indicate the importance of providing knowledge regarding health risk food for students and their parents in order to promote appropriate food consumption behavior among the students.

Keywords: food consumption, risky behavior, Suan Sunandha Rajabhat University, health risk

Procedia PDF Downloads 457
2099 Protective Role of Curcumin against Ionising Radiation of Gamma Ray

Authors: Turban Kar, Maitree Bhattacharyya

Abstract:

Curcumin, a dietary antioxidant has been identified as a wonder molecule to possess therapeutic properties protecting the cellular macromolecules from oxidative damage. In our experimental study, we have explored the effectiveness of curcumin in protecting the structural paradigm of Human Serum Albumin (HSA) when exposed to gamma irradiation. HSA, being an important transport protein of the circulatory system, is involved in binding of variety of metabolites, drugs, dyes and fatty acids due to the presence of hydrophobic pockets inside the structure. HSA is also actively involved in the transportation of drugs and metabolites to their targets, because of its long half-life and regulation of osmotic blood pressure. Gamma rays, in its increasing concentration, results in structural alteration of the protein and superoxide radical generation. Curcumin, on the other hand, mitigates the damage, which has been evidenced in the following experiments. Our study explores the possibility for protection by curcumin during the molecular and conformational changes of HSA when exposed to gamma irradiation. We used a combination of spectroscopic methods to probe the conformational ensemble of the irradiated HSA and finally evaluated the extent of restoration by curcumin. SDS - PAGE indicated the formation of cross linked aggregates as a consequence of increasing exposure of gamma radiation. CD and FTIR spectroscopy inferred significant decrease in alpha helix content of HSA from 57% to 15% with increasing radiation doses. Steady state and time resolved fluorescence studies complemented the spectroscopic measurements when lifetime decay was significantly reduced from 6.35 ns to 0.37 ns. Hydrophobic and bityrosine study showed the effectiveness of curcumin for protection against radiation induced free radical generation. Moreover, bityrosine and hydrophobic profiling of gamma irradiated HSA in presence and absence of curcumin provided light on the formation of ROS species generation and the protective (magical) role of curcumin. The molecular mechanism of curcumin protection to HSA from gamma irradiation is yet unknown, though a possible explanation has been proposed in this work using Thioflavin T assay. It was elucidated, that when HSA is irradiated at low dose of gamma radiation in presence of curcumin, it is capable of retaining the native characteristic properties to a greater extent indicating stabilization of molecular structure. Thus, curcumin may be utilized as a therapeutic strategy to protect cellular proteins.

Keywords: Bityrosine content, conformational change, curcumin, gamma radiation, human serum albumin

Procedia PDF Downloads 139
2098 Performance of the Photovoltaic Module under Different Shading Patterns

Authors: E. T. El Shenawy, O. N. A. Esmail, Adel A. Elbaset, Hesham F. A. Hamed

Abstract:

Generation of the electrical energy based on photovoltaic (PV) technology has been increased over the world due to either the continuous reduction in the traditional energy sources in addition to the pollution problems related to their usage, or the clean nature and safe usage of the PV technology. Also, PV systems can generate clean electricity in the site of use without any transmission, which can be considered cost effective than other generation systems. The performance of the PV system is highly affected by the amount of solar radiation incident on it. Completely or partially shaded PV systems can affect its output. The PV system can be shaded by trees, buildings, dust, incorrect system configuration, or other obstacles. The present paper studies the effect of the partial shading on the performance of a thin film PV module under climatic conditions of Cairo, Egypt. This effect was measured and evaluated according to practical measurement of the characteristic curves such as current-voltage and power-voltage for two identical PV modules (with and without shading) placed at the same time on one mechanical structure for comparison. The measurements have been carried out for the following shading patterns; half cell (bottom, middle, and top of the PV module); complete cell; and two adjacent cells. The results showed that partially shading the PV module changes the shapes of the I-V and P-V curves and produces more than one maximum power point, that can disturb the traditional maximum power point trackers. Also, the output power from the module decreased according to the incomplete solar radiation reaching the PV module due to shadow patterns. The power loss due shading was 7%, 22%, and 41% for shading of half-cell, one cell, and two adjacent cells of the PV module, respectively.

Keywords: I-V measurements, PV module characteristics, PV module power loss, PV module shading

Procedia PDF Downloads 119
2097 A Case Study of Response to Dual Genotype Chronic Hepatitis C/HIV Co-Infection to Fixed Dose Sofosbuvir/Ledipasvir

Authors: Tabassum Yasmin, Hamid Pahlevan

Abstract:

HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

Procedia PDF Downloads 179
2096 Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain

Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

Abstract:

Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

Procedia PDF Downloads 343
2095 Comparison of FNTD and OSLD Detectors' Responses to Light Ion Beams Using Monte Carlo Simulations and Exprimental Data

Authors: M. R. Akbari, H. Yousefnia, A. Ghasemi

Abstract:

Al2O3:C,Mg fluorescent nuclear track detector (FNTD) and Al2O3:C optically stimulated luminescence detector (OSLD) are becoming two of the applied detectors in ion dosimetry. Therefore, the response of these detectors to hadron beams is highly of interest in radiation therapy (RT) using ion beams. In this study, these detectors' responses to proton and Helium-4 ion beams were compared using Monte Carlo simulations. The calculated data for proton beams were compared with Markus ionization chamber (IC) measurement (in water phantom) from M.D. Anderson proton therapy center. Monte Carlo simulations were performed via the FLUKA code (version 2011.2-17). The detectors were modeled in cylindrical shape at various depths of the water phantom without shading each other for obtaining relative depth dose in the phantom. Mono-energetic parallel ion beams in different incident energies (100 MeV/n to 250 MeV/n) were collided perpendicularly on the phantom surface. For proton beams, the results showed that the simulated detectors have over response relative to IC measurements in water phantom. In all cases, there were good agreements between simulated ion ranges in the water with calculated and experimental results reported by the literature. For proton, maximum peak to entrance dose ratio in the simulated water phantom was 4.3 compared with about 3 obtained from IC measurements. For He-4 ion beams, maximum peak to entrance ratio calculated by both detectors was less than 3.6 in all energies. Generally, it can be said that FLUKA is a good tool to calculate Al2O3:C,Mg FNTD and Al2O3:C OSLD detectors responses to therapeutic proton and He-4 ion beams. It can also calculate proton and He-4 ion ranges with a reasonable accuracy.

Keywords: comparison, FNTD and OSLD detectors response, light ion beams, Monte Carlo simulations

Procedia PDF Downloads 324
2094 Study of Natural Radioactive and Radiation Hazard Index of Soil from Sembrong Catchment Area, Johor, Malaysia

Authors: M. I. A. Adziz, J. Sharib Sarip, M. T. Ishak, D. N. A. Tugi

Abstract:

Radiation exposure to humans and the environment is caused by natural radioactive material sources. Given that exposure to people and communities can occur through several pathways, it is necessary to pay attention to the increase in naturally radioactive material, particularly in the soil. Continuous research and monitoring on the distribution and determination of these natural radionuclides' activity as a guide and reference are beneficial, especially in an accidental exposure. Surface soil/sediment samples from several locations identified around the Sembrong catchment area were taken for the study. After 30 days of secular equilibrium with their daughters, the activity concentrations of the naturally occurring radioactive material (NORM) members, i.e. ²²⁶Ra, ²²⁸Ra, ²³⁸U, ²³²Th, and ⁴⁰K, were measured using high purity germanium (HPGe) gamma spectrometer. The results obtained showed that the radioactivity concentration of ²³⁸U ranged between 17.13 - 30.13 Bq/kg, ²³²Th ranged between 22.90 - 40.05 Bq/kg, ²²⁶Ra ranged between 19.19 - 32.10 Bq/kg, ²²⁸Ra ranged between 21.08 - 39.11 Bq/kg and ⁴⁰K ranged between 9.22 - 51.07 Bq/kg with average values of 20.98 Bq/kg, 27.39 Bq/kg, 23.55 Bq/kg, 26.93 Bq/kg and 23.55 Bq/kg respectively. The values obtained from this study were low or equivalent to previously reported in previous studies. It was also found that the mean/mean values obtained for the four parameters of the Radiation Hazard Index, namely radium equivalent activity (Raeq), external dose rate (D), annual effective dose and external hazard index (Hₑₓ), were 65.40 Bq/kg, 29.33 nGy/h, 19.18 ¹⁰⁻⁶Sv and 0.19 respectively. These obtained values are low compared to the world average values and the values of globally applied standards. Comparison with previous studies (dry season) also found that the values for all four parameters were low and equivalent. This indicates the level of radiation hazard in the area around the study is safe for the public.

Keywords: catchment area, gamma spectrometry, naturally occurring radioactive material (NORM), soil

Procedia PDF Downloads 83
2093 Deltamethrin-Induces Oxidative Stress to the Freshwater Ciliate Model: Paramecium tetraurelia

Authors: Amamra Ryma, Djebar Mohamed Reda, Moumeni Ouissem, Otmani Hadjer, Berrebbah Houria

Abstract:

The problem of environmental contamination by the excessive use of organics cannot be neglected. Extensive application is usually companied with serious problems and health risk. It is established that many chemicals, in common use, can produce some toxic effects on biological systems through their mode of action or by production of free radicals that damage all cell compounds. Deltamethrin, a widely used type II pyrethroid pesticide, is one of the most common contaminants in freshwater aquatic system. In this study, we investigate the effects of deltamethrin exposure on the induction of oxidative stress to the freshwater ciliate Paramecium tetraurelia. After the treatment of paramecium cells with increasing concentrations of insecticide, we followed up the growth kinetics, generation time and the percentage response. Also, we studied the variation in biomarkers of stress such as: GSH content, GST, GPX and CAT activities. Our results showed a significant decrease in the proliferation of cells correlated by the decrease in generation number and the increase in generation time. Also, we noted an inhibition in the percentage response. The monitoring of biomarkers revealed depletion in GSH content in a proportional and dose dependent manner accompanied by an increase in the GST activity. In parallel, a strong induction in the CAT and GPX activities was noted specially for the highest dose. In summary, under the current experimental conditions, deltamethrin is highly toxic to the freshwater ciliate Paramecium tetraurelia. Exposure to low concentrations showed significant adverse on growth accompanied with the induction of oxidative damage supported by the decrease in GSH content and the intensification of the antioxidant enzymes.

Keywords: deltamethrin, Paramecium tetraurelia, growth, oxidative stress, biomarkers, antioxidant

Procedia PDF Downloads 448
2092 Anticancer Effect of Resveratrol-Loaded Gelatin Nanoparticles in NCI-H460 Non-Small Cell Lung Carcinoma Cell Lines

Authors: N. Rajendra Prasad

Abstract:

Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

Procedia PDF Downloads 432
2091 Assessment of Cardioprotective Effect of Deferiprone on Doxorubicin-Induced Cardiac Toxicity in a Rat Model

Authors: Sadaf Kalhori

Abstract:

Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

Procedia PDF Downloads 120
2090 The Immunosuppressive Effects of Silymarin with Rapamaycin on the Proliferation and Apoptosis of T Cell

Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

Abstract:

Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

Procedia PDF Downloads 248
2089 Study of the Genotoxic Potential of Plant Growth Regulator Ethephon

Authors: Mahshid Hodjat, Maryam Baeeri, Mohammad Amin Rezvanfar, Mohammad Abdollahi

Abstract:

Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. The toxicity of organophosphate compounds is mostly attributed to their potent inhibition of acetylcholinesterase and their involvement in neurodegenerative disease. Although there are few reports on butyrylcholinesterase inhibitory role of ethephon, still there is no evidence on neurotoxicity and genotoxicity of this compound. The aim of the current study is to assess the potential genotoxic effect of ethephon using two genotoxic endpoints; γH2AX expression and comet assay on embryonic murine fibroblast. γH2AX serves as an early and sensitive biomarker for evaluating the genotoxic effects of chemicals. Oxidative stress biomarkers, including intracellular reactive oxygen species, lipid peroxidation and antioxidant capacity were also examined. The results showed a significant increase in cell proliferation 24h post-treatment with 10, 40,160µg/ml ethephon. The γH2AX expression and γH2AX foci count per cell were increased at low concentration of ethephon that was concomitant with increased DNA damage break at 40 and 160 µg/ml as illustrated by increased comet tail moment. A significant increase in lipid peroxidation and ROS formation were observed at 160 µg/ml and higher doses. The results showed that low-dose of ethephon promoted cell proliferation while induce DNA damage, raising the possibility of ethephon mutagenicity. Ethephon-induced genotoxic effect of low dose might not related to oxidative damage. However, ethephon was found to increase oxidative stress at higher doses, lead to cellular cytotoxicity. Taken together, all data indicated that ethylene, deserves more attention as a plant regulator with potential genotoxicity for which appropriate control is needed to reduce its usage.

Keywords: ethephon, DNA damage, γH2AX, oxidative stress

Procedia PDF Downloads 293
2088 Experimental Research of Smoke Impact on the Performance of Cylindrical Eight Channel Cyclone

Authors: Pranas Baltrėnas, Dainius Paliulis

Abstract:

Cyclones are widely used for separating particles from gas in energy production objects. Efficiency of normal centrifugal air cleaning devices ranges from 85 to 90%, but weakness of many cyclones is low collection efficiency of particles less than 10 μm in diameter. Many factors have impact on cyclone efficiency – humidity, temperature, gas (air) composition, airflow velocity and etc. Many scientists evaluated only effect of origin and size of PM on cyclone efficiency. Effect of gas (air) composition and temperature on cyclone efficiency still demands contributions. Complex experimental research on efficiency of cylindrical eight-channel system with adjustable half-rings for removing fine dispersive particles (< 20 μm) was carried out. The impact of gaseous smoke components on removal of wood ashes was analyzed. Gaseous components, present in the smoke mixture, with the dynamic viscosity lower than that of same temperature air, decrease the d50 value, simultaneously increasing the overall particulate matter removal efficiency in the cyclone, i.e. this effect is attributed to CO2 and CO, while O2 and NO have the opposite effect. Air temperature influences the d50 value, an increase in air temperature yields an increase in d50 value, i.e. the overall particulate matter removal efficiency declines, the reason for this being an increasing dynamic air viscosity. At 120 °C temperature the d50 value is approximately 11.8 % higher than at air temperature of 20 °C. With an increase in smoke (gas) temperature from 20 °C to 50 °C, the aerodynamic resistance in a 1-tier eight-channel cylindrical cyclone drops from 1605 to 1380 Pa, from 1660 to 1420 Pa in a 2-tier eight-channel cylindrical cyclone, from 1715 to 1450 Pa in a 3-tier eight-channel cylindrical cyclone. The reason for a decline in aerodynamic resistance is the declining gas density. The aim of the paper is to analyze the impact of gaseous smoke components on the eight–channel cyclone with tangential inlet.

Keywords: cyclone, adjustable half-rings, particulate matter, efficiency, gaseous compounds, smoke

Procedia PDF Downloads 273
2087 Effect of Tooth Bleaching Agents on Enamel Demineralisation

Authors: Najlaa Yousef Qusti, Steven J. Brookes, Paul A. Brunton

Abstract:

Background: Tooth discoloration can be an aesthetic problem, and tooth whitening using carbamide peroxide bleaching agents are a popular treatment option. However, there are concerns about possible adverse effects such as demineralisation of the bleached enamel; however, the cause of this demineralisation is unclear. Introduction: Teeth can become stained or discoloured over time. Tooth whitening is an aesthetic solution for tooth discoloration. Bleaching solutions of 10% carbamide peroxide (CP) have become the standard agent used in dentist-prescribed and home-applied ’vital bleaching techniques’. These materials release hydrogen peroxide (H₂O₂), the active whitening agent. However, there is controversy in the literature regarding the effect of bleaching agents on enamel integrity and enamel mineral content. The purpose of this study was to establish if carbamide peroxide bleaching agents affect the acid solubility of enamel (i.e., make teeth more prone to demineralisation). Materials and Methods: Twelve human premolar teeth were sectioned longitudinally along the midline and varnished to leave the natural enamel surface exposed. The baseline behavior of each tooth half in relation to its demineralisation in acid was established by sequential exposure to 4 vials containing 1ml of 10mM acetic acid (1 minute/vial). This was followed by exposure to 10% CP for 8 hours. After washing in distilled water, the tooth half was sequentially exposed to 4 further vials containing acid to test if the acid susceptibility of the enamel had been affected. The corresponding tooth half acted as a control and was exposed to distilled water instead of CP. The mineral loss was determined by measuring [Ca²⁺] and [PO₄³⁻] released in each vial using a calcium ion-selective electrode and the phosphomolybdenum blue method, respectively. The effect of bleaching on the tooth surfaces was also examined using SEM. Results: Exposure to carbamide peroxide did not significantly alter the susceptibility of enamel to acid attack, and SEM of the enamel surface revealed a slight alteration in surface appearance. SEM images of the control enamel surface showed a flat enamel surface with some shallow pits, whereas the bleached enamel appeared with an increase in surface porosity and some areas of mild erosion. Conclusions: Exposure to H₂O₂ equivalent to 10% CP does not significantly increase subsequent acid susceptibility of enamel as determined by Ca²⁺ release from the enamel surface. The effects of bleaching on mineral loss were indistinguishable from distilled water in the experimental system used. However, some surface differences were observed by SEM. The phosphomolybdenum blue method for phosphate is compromised by peroxide bleaching agents due to their oxidising properties. However, the Ca²⁺ electrode is unaffected by oxidising agents and can be used to determine the mineral loss in the presence of peroxides.

Keywords: bleaching, carbamide peroxide, demineralisation, teeth whitening

Procedia PDF Downloads 109
2086 Genetics of Pharmacokinetic Drug-Drug Interactions of Most Commonly Used Drug Combinations in the UK: Uncovering Unrecognised Associations

Authors: Mustafa Malki, Ewan R. Pearson

Abstract:

Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

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