Search results for: dose%20optimization

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

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

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

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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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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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

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

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

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Authors: Tabassum Yasmin, Hamid Pahlevan

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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

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

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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

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

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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

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

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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

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

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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

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Authors: Sadaf Kalhori

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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

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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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

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Authors: Suman Som, Abhijit Maity, Sunil B. Daschakraborty, Sujit Chaudhuri, Manik Pradhan

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Background: Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. Currently H. pylori infection is detected by both invasive and non-invasive way but the diagnostic accuracy is not up to the mark. Aim: To set up an optimal diagnostic cut-off value of 13C-Urea Breath Test to detect H. pylori infection and evaluate a novel c-PDR methodology to overcome of inconclusive grey zone. Materials and Methods: All 83 subjects first underwent upper-gastrointestinal endoscopy followed by rapid urease test and histopathology and depending on these results; we classified 49 subjects as H. pylori positive and 34 negative. After an overnight, fast patients are taken 4 gm of citric acid in 200 ml water solution and 10 minute after ingestion of the test meal, a baseline exhaled breath sample was collected. Thereafter an oral dose of 75 mg 13C-Urea dissolved in 50 ml water was given and breath samples were collected upto 90 minute for 15 minute intervals and analysed by laser based high precisional cavity enhanced spectroscopy. Results: We studied the excretion kinetics of 13C isotope enrichment (expressed as δDOB13C ‰) of exhaled breath samples and found maximum enrichment around 30 minute of H. pylori positive patients, it is due to the acid mediated stimulated urease enzyme activity and maximum acidification happened within 30 minute but no such significant isotopic enrichment observed for H. pylori negative individuals. Using Receiver Operating Characteristic (ROC) curve an optimal diagnostic cut-off value, δDOB13C ‰ = 3.14 was determined at 30 minute exhibiting 89.16% accuracy. Now to overcome grey zone problem we explore percentage dose of 13C recovered per hour, i.e. 13C-PDR (%/hr) and cumulative percentage dose of 13C recovered, i.e. c-PDR (%) in exhaled breath samples for the present 13C-UBT. We further explored the diagnostic accuracy of 13C-UBT by constructing ROC curve using c-PDR (%) values and an optimal cut-off value was estimated to be c-PDR = 1.47 (%) at 60 minute, exhibiting 100 % diagnostic sensitivity , 100 % specificity and 100 % accuracy of 13C-UBT for detection of H. pylori infection. We also elucidate the gastric emptying process of present 13C-UBT for H. pylori positive patients. The maximal emptying rate found at 36 minute and half empting time of present 13C-UBT was found at 45 minute. Conclusions: The present study exhibiting the importance of c-PDR methodology to overcome of grey zone problem in 13C-UBT for accurate determination of infection without any risk of diagnostic errors and making it sufficiently robust and novel method for an accurate and fast non-invasive diagnosis of H. pylori infection for large scale screening purposes.

Keywords: 13C-Urea breath test, c-PDR methodology, grey zone, Helicobacter pylori

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

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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 291

Authors: Mustafa Malki, Ewan R. Pearson

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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

Procedia PDF Downloads 143

Authors: Anaelle Gabet, Helene Metivier, Christine De Brauer, Gilles Mailhot, Marcello Brigante

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The presence of micropollutants in surface waters has been widely reported around the world, particularly downstream from wastewater treatment plants (WWTPs). Rural WWTPs constitute more than 90 % of the total WWTPs in France. Like conventional ones, they are not able to fully remove micropollutants. Estrogens are excreted by human beings every day and several studies have highlighted their endocrine disruption properties on river wildlife. They are mainly estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2). Rural WWTPs require cheap and robust tertiary processes. UVC activation of H₂O₂ for HO· generation, a very reactive molecule, has demonstrated its effectiveness. However, UVC rays are dangerous to manipulate and energy-consuming. This is why the ability of UVA rays was investigated in this study. Moreover, the use of S₂O₈²⁻ for SO₄·- generation as an alternative to HO· has emerged in the last few years. Such processes have been widely studied on a lab scale. However, pilot-scale works constitute fewer studies. This study was carried out on a 20-L pilot composed of a 1.12-L UV reactor equipped with a polychromatic UVA lamp or a monochromatic (254 nm) UVC lamp fed in recirculation. Degradation rates of a mixture of spiked E1, E2 and EE2 (5 µM each) were followed by HPLC-UV. Results are expressed in UV dose (mJ.cm-2) received by the compounds of interest to compare UVC and UVA. In every system, estrogen degradation rates followed pseudo-first-order rates. First, experiments were carried out in tap water. All estrogens underwent photolysis under UVC rays, although E1 photolysis is higher. However, only very weak photolysis was observed under UVA rays. Preliminary studies on both oxidants have shown that S₂O₈²⁻ photolysis constants are higher than H₂O₂ under both UVA and UVC rays. Therefore, estrogen degradation rates are about ten times higher in the presence of 1 mM of S₂O₈²⁻ than with one mM of H₂O₂ under both radiations. In the same conditions, the mixture of interest required about 40 times higher UV dose when using UVA rays compared to UVC. However, the UVA/S₂O₈²⁻ system only requires four times more UV dose than the conventional UVC/H₂O₂ system. Further studies were carried out in WWTP effluent with the UVC lamp. When comparing these results to the tap water ones, estrogen degradation rates were more inhibited in the S₂O₈²⁻ system than with H₂O₂. It seems that SO₄·- undergo higher quenching by a real effluent than HO·. Preliminary experiments have shown that natural organic matter is mainly responsible for the radical quenching and that HO and SO₄ both had similar second-order reaction rate constants with dissolved organic matter. However, E1, E2 and EE2 second-order reaction rate constants are about ten times lower with SO₄ than with HO. In conclusion, the UVA/S₂O₈²⁻ system showed encouraging results for the use of UVA rays but further studies in WWTP effluent have to be carried out to confirm this interest. The efficiency of other pollutants in the real matrix also needs to be investigated.

Keywords: AOPs, decontamination, estrogens, radicals, wastewater

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Authors: Kandi Sridhar, Charles Albert Linton

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Grapes are excellent sources of bioactive compounds, which have been suggested to be responsible for lowering the risk of chronic diseases. Fresh and freeze-dried extracts of Kyoho and Jubilee, commercial grape varieties available in Taiwan and attractive for their quality berries, were investigated for their total phenolics and total flavonoids contents and related dose-dependent antioxidants properties using various in vitro assays. The efficiency of the extraction yield ranged from 7.10 % to 25.53 % (w/w), depending on solvent used. Fresh samples of Kyoho and Jubilee exhibited total polyphenolic contents (351.56 ± 23.08 and 328.67 ± 16.54 µg GAE/mL, respectively), whereas Kyoho freeze-dried methanol: water extracts contains the good levels of total flavonoids (4767.82 ± 22.20 µg QE/mL). Kyoho and Jubilee freeze-dried extracts exhibited the highest total flavonoid contents. There was a weak correlation between total phenolic and flavonoid assays (r= -0.05, R2 = 0.02, p > 0.05). Kyoho fresh and freeze-dried samples showed the DPPH (11.51 – 77.82 %), superoxide scavenging activity (33.61 – 81.95 %), and total antioxidant inhibition (92.01 – 99.28 %), respectively. Total flavonoids were statistically correlated with EC50 DPPH scavenging radicals (r =0.91, p < 0.01), EC50 nitric oxide (r = 0.25, p > 0.05), and EC50 lipid peroxidation radicals (r = 0.38, p > 0.05). These results suggested that the two commercial grape cultivars in Taiwan could be used as a good source of natural antioxidants. Thus, consumption of grapes as a source antioxidant might lower the risk of chronic diseases. Moreover, future studies will investigate and develop phenolic acid profile for the cultivars in Taiwan.

Keywords: antioxidants, EC50 radical scavenging activity, grape cultivars, total phenolics

Procedia PDF Downloads 164

Authors: G. H. Haddadi, S. Sajadi, R. Fardid, Z. Haddadi

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The heart is a radiosensitive organ, and its damage is a dose-limiting factor in radiotherapy. Different side effects including vascular plaque and heart fibrosis occur in patients with thorax irradiation. The present study aimed to evaluate the radioprotective efficacy of Hesperidin (HES), a naturally occurring citrus flavanoglycone, against γ-radiation induced tissue damage in the heart of male rats. Sixty-eight rats were divided into four groups. The rats in group 1 received PBS, and those in group 2 received HES. Also, the rats in group 3 received PBS and underwent γ-irradiation, and those in group 4 received HES and underwent γ-irradiation. They were exposed to 20 Gy γ-radiation using a single fraction cobalt-60 unit, and the dose of Hesperidin was (100 mg/kg/d, orally) for 7 days prior irradiation. Each group was divided into two subgroups. Samplings of rats in subgroup A was done 4-6 hours after irradiation. The samples were sent to laboratory for determination of Troponin’s I (TnI) serum level changes as a cardiac biomarker. The remaining animals (subgroups B) were sacrificed 8 weeks after radiotherapy for histopathological evaluation. In group 3, TnI obviously increased in comparison with group 1 (p < 0.05). The comparison of groups 1 and 4 showed no significant difference. Evaluation of histopathological parameters in subgroup B showed significant differences between groups 1 and 3 in some of the cases. Inflammation (p=0.008), pericardial effusion (p=0.001) and vascular plaque (p=0.001) increased in the rats exposed to 20 Gy γ-irradiation. Using oral administration of HES significantly decreased all the above factors when compared to group 4 (P > 0.016). Administration of 100 mg/kg/day Hesperidin for 7 days resulted in decreased Troponin I and radiation heart injury. This agent may have protective effects against radiation-induced heart damage.

Keywords: hesperidin, radioprotector, troponin I, cardiac inflammation, vascular plaque

Procedia PDF Downloads 234

Authors: Sebnem Canikli Engin, Mutlu Sevinc, Hasan Guzelbektes

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In this study, we aim to define the effects of erythromycin and bethanechol which are prokinetic agents, on the value of abomasal discharge in healthy, diarrhea and premature calves. In the work, 5 healty calves, 12 diarrheaic calves and 12 premature calves, amounting to a total of 29 calves. In healty calves work; the same 5 calves were used for controlled, erythromycin and bethanechol studies (there was a 48-hour waiting period between each work). In diarrheic calves work; 12 diarrheic calves were used during the study (4 of them for control group, 4 of them bethanechol group and last 4 calves erythromycin group). In premature calves works; 12 premature calves were used during the study (4 of them for control group, 4 of them bethanechol group and last 4 calves erythromycin group). 10 mg/kg IM dose of erythromycin were applied to each erythromycin group, 0,07 mg/kg IM dose of bethanechol were applied on bethanechol group. No drugs were applied to the control group and substitution milk was given to all calves. 50 mg/kg acetominophen and 25 gram/L glucose have been added into the substitution milk to evaluate the speed of gastrointestinal motility with the test results of absorptions of acetominophen and glucose. The blood samples have been taken before substitution milk application and 30, 60, 90, 120, 180, 240 and 300 minutes after substitution milk application. Respiratory rates and number of heartbeats were also recorded during the test time. No changes were observed in the number of heartbeats, respiratory rates and general conditions for all groups after drug application. It is observed that, the feces of some calves became slightly watery and viscous and premature calves generaly defecated after 180 minutes. When Cmax, Tmax and AUC values of acetaminophen and glucose are compared with control group’s after applying erythromycin on the calves in the premature group, we obtain higher Cmax (P<0,05), shorter Tmax and greather AUC (P>0,05) values. In conclusion, according to clinical and laboratory findings, it may be stated that the application of 10 mg/kg doze of erythromycin IM has provided faster abomazal emptying in premature calves.

Keywords: abomazal emptying, bethanechol, calf, erythromycin

Procedia PDF Downloads 317

Authors: Ya'u Muhammad, Umar Umar A. Mallammadori, Dahiru Mansur

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Effect of kaempferol on haematological parameters in two weeks old broiler chickens with experimental Eimeria tenella infection was evaluated in this study. Sixty-day old broilers were randomly allotted into six groups (I-VI) of ten broilers each and brooded for two weeks with commercial broiler feed (vital feed®) and provided water ad libitum. At two weeks of age broilers in group 1 were neither infected nor treated. Broilers in groups II-VI were infected with Eimeria tenella sporulated oocyst (104/ml) via oral inoculation. After infection was established, broilers in groups II-IV were treated orally with 1 mg/kg, 1.5 mg/kg, and 2 mg/kg of kaempferol, respectively. Broilers in group V were treated for five days with amprolium, 1.25 g/L in drinking water. Broilers in group VI were administered normal saline, 5 ml/kg per os for five days. Five days post infection; all broilers were sacrificed by severing their jugular veins. Blood sample from each bird was collected in EDTA container for haematology. Caecal contents were harvested and used to determine the lesion score and caecal Oocyst count respectively. Data obtained was analyzed using pad prism version 5.0. Mean Packed Cell Volume (PCV), haemoglobin (Hb) concentration, and Red Blood Cell (RBC) count significantly (P < 0.05) increased in groups II, III, and IV in a dose dependent manner. Similarly, PCV, Hb concentration, and RBC count significantly (P < 0.05) increased in groups II, III, and IV when compared to VI. No significant (P > 0.05) difference in the mean values of PCV, Hb and RBC count were recorded between groups treated with kaempferol and group V. Caecal Oocyst counts and lesion scores reduced significantly (P < 0.05) in groups II, III, and IV in a dose dependent manner. It was therefore observed in this study that kaempferol improved haematological parameters and reduced Oocyst count as well as the lesion scores in broilers infected with Eimeria tenella.

Keywords: broilers, Eimeria tenella, kaempferol, lesion scores, oocyst count,

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Authors: Girmaye Abebe, Brook Lemma

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Adsorption of phosphorus (P as PO43-) in filter cake was studied to assess the media's capability in removing phosphorous from wastewaters. The composition of the filter cake that was generated from alum manufacturing process as waste residue has high amount of silicate from the complete silicate analysis of the experiment. Series of batches adsorption experiments were carried out to evaluate parameters that influence the adsorption capacity of PO43-. The factors studied include the effect of contact time, adsorbent dose, thermal pretreatment of the adsorbent, neutralization of the adsorbent, initial PO43- concentration, pH of the solution and effect of co-existing anions. Results showed that adsorption of PO43- is fairly rapid in first 5 min and after that it increases slowly to reach the equilibrium in about 1 h. The treatment efficiency of PO43- was increased with adsorbent extent. About 90% removal efficiency was increased within 1 h at an optimum adsorbent dose of 10 g/L for initial PO43- concentration of 10 mg/L. The amount of PO43- adsorbed increased with increasing initial PO43- concentration. Heat treatment and surface neutralization of the adsorbent did not improve the PO43- removal capacity and efficiency. The percentage of PO43- removal remains nearly constant within the pH range of 3-8. The adsorption data at ambient pH were well fitted to the Langmuir Isotherm and Dubinin–Radushkevick (D–R) isotherm model with a capacity of 25.84 and 157.55 mg/g of the adsorbent respectively. The adsorption kinetic was found to follow a pseudo-second-order rate equation with an average rate constant of 3.76 g.min−1.mg−1. The presence of bicarbonate or carbonate at higher concentrations (10–1000 mg/L) decreased the PO43- removal efficiency slightly while other anions (Cl-, SO42-, and NO3-) have no significant effect within the concentration range tested. The overall result shows that the filter cake is an efficient PO43- removing adsorbent against many parameters.

Keywords: wastewater, filter cake, adsorption capacity, phosphate (PO43-)

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Authors: Reza Fardid, Aliyeh Alipour

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Introduction: Coronary heart disease (CHD) is the most common and deadliest diseases. A coronary angiography is an important tool for the diagnosis and treatment of this disease. Because angiography is performed by exposure to ionizing radiation, it can lead to harmful effects. Ionizing radiation induces double-stranded breaks in DNA, which is a potentially life-threatening injury. The purpose of the present study is an investigation of the phosphorylation of histone H2AX in the location of the double-stranded break in Peripheral blood lymphocytes as an indication of Biological effects of radiation on angiography patients. Materials and Methods: This method is based on measurement of the phosphorylation of histone (gamma-H2AX, gH2AX) level on serine 139 after formation of DNA double-strand break. 5 cc of blood from 24 patients with angiography were sampled before and after irradiation. Blood lymphocytes were removed, fixed and were stained with specific ϒH2AX antibodies. Finally, ϒH2AX signal as an indicator of the double-strand break was measured with Flow Cytometry Technique. Results and discussion: In all patients, an increase was observed in the number of breaks in double-stranded DNA after irradiation (20.15 ± 14.18) compared to before exposure (1.52 ± 0.34). Also, the mean of DNA double-strand break was showed a linear correlation with DAP. However, although induction of DNA double-strand breaks associated with radiation dose in patients, the effect of individual factors such as radiosensitivity and regenerative capacity should not be ignored. If in future we can measure DNA damage response in every patient angiography and it will be used as a biomarker patient dose, will look very impressive on the public health level. Conclusion: Using flow cytometry readings which are done automatically, it is possible to detect ϒH2AX in the number of blood cells. Therefore, the use of this technique could play a significant role in monitoring patients.

Keywords: coronary angiography, DSB of DNA, ϒH2AX, ionizing radiation

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Authors: S. Hatamikia, A. Biguri, H. Furtado, G. Kronreif, J. Kettenbach, W. Birkfellner

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Nowadays, three dimensional Cone Beam CT (CBCT) has turned into a widespread clinical routine imaging modality for interventional radiology. In conventional CBCT, a circular sourcedetector trajectory is used to acquire a high number of 2D projections in order to reconstruct a 3D volume. However, the accumulated radiation dose due to the repetitive use of CBCT needed for the intraoperative procedure as well as daily pretreatment patient alignment for radiotherapy has become a concern. It is of great importance for both health care providers and patients to decrease the amount of radiation dose required for these interventional images. Thus, it is desirable to find some optimized source-detector trajectories with the reduced number of projections which could therefore lead to dose reduction. In this study we investigate some source-detector trajectories with the optimal arbitrary orientation in the way to maximize performance of the reconstructed image at particular regions of interest. To achieve this approach, we developed a box phantom consisting several small target polytetrafluoroethylene spheres at regular distances through the entire phantom. Each of these spheres serves as a target inside a particular region of interest. We use the 3D Point Spread Function (PSF) as a measure to evaluate the performance of the reconstructed image. We measured the spatial variance in terms of Full-Width-Half-Maximum (FWHM) of the local PSFs each related to a particular target. The lower value of FWHM shows the better spatial resolution of reconstruction results at the target area. One important feature of interventional radiology is that we have very well-known imaging targets as a prior knowledge of patient anatomy (e.g. preoperative CT) is usually available for interventional imaging. Therefore, we use a CT scan from the box phantom as the prior knowledge and consider that as the digital phantom in our simulations to find the optimal trajectory for a specific target. Based on the simulation phase we have the optimal trajectory which can be then applied on the device in real situation. We consider a Philips Allura FD20 Xper C-arm geometry to perform the simulations and real data acquisition. Our experimental results based on both simulation and real data show our proposed optimization scheme has the capacity to find optimized trajectories with minimal number of projections in order to localize the targets. Our results show the proposed optimized trajectories are able to localize the targets as good as a standard circular trajectory while using just 1/3 number of projections. Conclusion: We demonstrate that applying a minimal dedicated set of projections with optimized orientations is sufficient to localize targets, may minimize radiation.

Keywords: CBCT, C-arm, reconstruction, trajectory optimization

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: G. Traini, G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, S. M. Valle, C. Voena, V. Patera

Abstract:

In Particle Therapy (PT) treatments a large amount of secondary particles, whose emission point is correlated to the dose released in the crossed tissues, is produced. The measurement of the secondary charged fragments component could represent a valid technique to monitor the beam range during the PT treatments, that is a still missing item in the clinical practice. A sub-millimetrical precision on the beam range measurement is required to significantly optimise the technique and to improve the treatment quality. In this contribution, a detector, named Dose Profiler (DP), is presented. It is specifically planned to monitor on-line the beam range exploiting the secondary charged particles produced in PT Carbon ions treatment. In particular, the DP is designed to track the secondary fragments emitted at large angles with respect to the beam direction (mainly protons), with the aim to reconstruct the spatial coordinates of the fragment emission point extrapolating the measured track toward the beam axis. The DP is currently under development within of the INSIDE collaboration (Innovative Solutions for In-beam Dosimetry in hadrontherapy). The tracker is made by six layers (20 × 20 cm²) of BCF-12 square scintillating fibres (500 μm) coupled to Silicon Photo-Multipliers, followed by two plastic scintillator layers of 6 mm thickness. A system of front-end boards based on FPGAs arranged around the detector provides the data acquisition. The detector characterization with cosmic rays is currently undergoing, and a data taking campaign with protons will take place in May 2017. The DP design and the performances measured with using MIPs and protons beam will be reviewed.

Keywords: fragmentation, monitoring, particle therapy, tracking

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Authors: Yi-An Liao, Lu-Wei Kuo, Yu-Jen Shih, Yao-Hui Huang

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Abstract—Imidacloprid (IMI, a widely used pesticide, iImidacloprid (IMI), a widely used pesticide, is known to affect the bee populations. A sulfate radical-based oxidation method was utilized to remove the commercial pesticide consisted of IMI, dimethylacetamide, N-methyl-2-pyrrolidone, and methanol (TOC0 = 497 ppm). The experimental results evidenced that sulfate radicals created by UV activation (254nm, 6.4 mW/cm2) of S2O82- could remove 97% of total organic carbon (TOC) from the synthetic wastewater in 4 h using 120 mM of oxidant dosage. The dose of oxidant, temperature and the light flux were the key factors to further improve the mineralization efficiency, while the ferrous ions decreased the efficacy of UV/S2O82- reaction due to the competition of UV-adsorption by complex formation of FeSO4+.s known to affect the bee populations. A sulfate radical-based oxidation method was utilized to remove the commercial pesticide consisted of IMI, dimethylacetamide, N-methyl-2-pyrrolidone, and methanol (TOC0 = 497 ppm). The experimental results evidenced that sulfate radicals created by UV activation (254nm, 6.4 mW/cm2) of S2O82- could remove 97% of total organic carbon (TOC) from the synthetic wastewater in 4 h using 120 mM of oxidant dosage. The dose of oxidant, temperature and the light flux were the key factors to further improve the mineralization efficiency, while the ferrous ions decreased the efficacy of UV/S2O82- reaction due to the competition of UV-adsorption by complex formation of FeSO4+.

Keywords: organic nitrogen, photochemical oxidation, imidacloprid, UV-persulfate, mineralization

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Authors: Houda Oueriemmi, Petra Susan Kidd, Carmen Trasar-Cepeda, Beatriz Rodríguez-Garrido, Mohamed Moussa, Ángeles Prieto-Fernández, Mohamed Ouessar

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Organic amendments are generally used for improving the fertility of arid and semi-arid soils. However, the price of farmyard manure, the organic amendment typically applied to many arid and semi-arid soils has highly increased in the last years. To investigate at field scale whether cheap, highly available organic amendments, such as sewage sludge compost and municipal solid waste compost, may be acceptable as substitutes for farmyard manure is therefore of great interest. A field plots experiment was carried out to assess the effects of a single application of three organic amendments on soil fertility, distribution of trace elements and on barley yield. Municipal solid waste compost (MSWC), farmyard manure (FYM) and sewage sludge compost (SSC) were applied at rates of 0, 20, 40 and 60 t ha⁻¹, and barley was cultivated in two consecutive years. Plant samples and soils were collected for laboratory analyses after two consecutive harvests. Compared with unamended soil, the application of the three organic residues improved the fertility of the topsoil, showing a significant dose-dependent increase of TOC, N, P contents up to the highest dose of 60 t ha⁻¹ (0.74%, 0.06% and 40 mg kg⁻¹, respectively). The enhancement of soil nutrient status impacted positively on grain yield (up to 51%). The distribution of trace elements in the soil, analysed by a sequential extraction procedure, revealed that the MSWC increased the acid-extractable Co and Cu and reducible Ni, while SSC increased reducible Co and Ni and oxidisable Cu, relative to the control soil.

Keywords: municipal solid waste compost, sewage sludge compost, fertility, trace metals

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Authors: A. Fomujong, P. Mobit, A. Ndlovu, R. Teboh

Abstract:

Purpose: Film’s unique qualities, such as tissue equivalence, high spatial resolution, near energy independence and comparatively less expensive dosimeter, ought to make it the preferred and widely used in radiotherapy centers in low and middle income countries (LMICs). This, however, is not always the case, as other factors that are often maybe taken for granted in advanced radiotherapy centers remain a challenge in LMICs. We explored the unique qualities of film dosimetry that can make it possible for one Institution to benefit from another’s protocols via collaboration. Methods: For simplicity, two Institutions were considered in this work. We used a single batch of films (EBT-XD) and established a calibration protocol, including scan protocols and calibration curves, using the radiotherapy delivery system at Institution A. We then proceeded and performed patient-specific QA for patients treated on system A (PSQA-A-A). Films from the same batch were then sent to a remote center for PSQA on radiotherapy delivery system B. Irradiations were done at Institution B and then returned to Institution A for processing and analysis (PSQA-B-A). The following points were taken into consideration throughout the process (a) A reference film was irradiated to a known dose on the same system irradiating the PSQA film. (b) For calibration, we utilized the one-scan protocol and maintained the same scan orientation of the calibration, PSQA and reference films. Results: Gamma index analysis using a dose threshold of 10% and 3%/2mm criteria showed a gamma passing rate of 99.8% and 100% for the PSQA-A-A and PSQA-B-A, respectively. Conclusion: This work demonstrates that one could use established film dosimetry protocols in one Institution, e.g., an advanced radiotherapy center and apply similar accuracies to irradiations performed at another institution, e.g., a center located in LMIC, which thus encourages collaboration between the two for worldwide patient benefits.

Keywords: collaboration, film dosimetry, LMIC, radiotherapy, calibration

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