Search results for: exposure dose
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3160

Search results for: exposure dose

2650 The Evaluation of Occupational Exposure of Chrome in Welders of Stainless Steels

Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

Abstract:

Introduction: Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) in steel was above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. Materials and Methods: The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) was used cytogenetic analysis of peripheral blood lymphocytes, gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistical analysis was used the Mann-Whitney U-test. Results: The mean Cr level in exposed group was 0.095 mmol/l (0.019 min-max 0.504). No value does exceed the average normal value. The average value Cr in urine was 7.9 mmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs 0.80% and CSA-type 0.96% vs 0.90%). In the number of total CA was observed statistical difference between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44%<1.82%<2.13%). There was observed a statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups (1.22% vs. 0.59%, P<0.05). Discussion and conclusions: The work place is usually higher source of exposure to harmful factors. Workers need consistently and checked frequently health control. In assessing the risk of adverse effects of metals is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: genotoxicity, chromium, stainless steels, welders

Procedia PDF Downloads 360
2649 All Types of Base Pair Substitutions Induced by γ-Rays in Haploid and Diploid Yeast Cells

Authors: Natalia Koltovaya, Nadezhda Zhuchkina, Ksenia Lyubimova

Abstract:

We study the biological effects induced by ionizing radiation in view of therapeutic exposure and the idea of space flights beyond Earth's magnetosphere. In particular, we examine the differences between base pair substitution induction by ionizing radiation in model haploid and diploid yeast Saccharomyces cerevisiae cells. Such mutations are difficult to study in higher eukaryotic systems. In our research, we have used a collection of six isogenic trp5-strains and 14 isogenic haploid and diploid cyc1-strains that are specific markers of all possible base-pair substitutions. These strains differ from each other only in single base substitutions within codon-50 of the trp5 gene or codon-22 of the cyc1 gene. Different mutation spectra for two different haploid genetic trp5- and cyc1-assays and different mutation spectra for the same genetic cyc1-system in cells with different ploidy — haploid and diploid — have been obtained. It was linear function for dose-dependence in haploid and exponential in diploid cells. We suggest that the differences between haploid yeast strains reflect the dependence on the sequence context, while the differences between haploid and diploid strains reflect the different molecular mechanisms of mutations.

Keywords: base pair substitutions, γ-rays, haploid and diploid cells, yeast Saccharomyces cerevisiae

Procedia PDF Downloads 147
2648 DNA of Hibiscus sabdariffa Damaged by Radiation from 900 MHz GSM Antenna

Authors: A. O. Oluwajobi, O. A. Falusi, N. A. Zubbair, T. Owoeye, F. Ladejobi, M. C. Dangana, A. Abubakar

Abstract:

The technology of mobile telephony has positively enhanced human life and reports on the bio safety of the radiation from their antennae have been contradictory, leading to serious litigations and violent protests by residents in several parts of the world. The crave for more information, as requested by WHO in order to resolve this issue, formed the basis for this study on the effect of the radiation from 900 MHz GSM antenna on the DNA of Hibiscus sabdariffa. Seeds of H. sabdariffa were raised in pots placed in three replicates at 100, 200, 300 and 400 metres from the GSM antennae in three selected test locations and a control where there was no GSM signal. Temperature (˚C) and the relative humidity (%) of study sites were measured for the period of study (24 weeks). Fresh young leaves were harvested from each plant at two, eight and twenty-four weeks after sowing and the DNA extracts were subjected to RAPD-PCR analyses. There were no significant differences between the weather conditions (temperature and relative humidity) in all the study locations. However, significant differences were observed in the intensities of radiations between the control (less than 0.02 V/m) and the test (0.40-1.01 V/m) locations. Data obtained showed that DNA of samples exposed to rays from GSM antenna had various levels of distortions, estimated at 91.67%. Distortions occurred in 58.33% of the samples between 2-8 weeks of exposure while 33.33% of the samples were distorted between 8-24 weeks exposure. Approximately 8.33% of the samples did not show distortions in DNA while 33.33% of the samples had their DNA damaged twice, both at 8 and at 24 weeks of exposure. The study showed that radiation from the 900 MHz GSM antenna is potent enough to cause distortions to DNA of H. sabdariffa even within 2-8 weeks of exposure. DNA damage was also independent of the distance from the antenna. These observations would qualify emissions from GSM mast as environmental hazard to the existence of plant biodiversities and all life forms in general. These results will trigger efforts to prevent further erosion of plant genetic resources which have been threatening food security and also the risks posed to living organisms, thereby making our environment very safe for our existence while we still continue to enjoy the benefits of the GSM technology.

Keywords: damage, DNA, GSM antenna, radiation

Procedia PDF Downloads 331
2647 Synergistic Effect of Doxorubicin-Loaded Silver Nanoparticles – Polymeric Conjugates on Breast Cancer Cells

Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

Abstract:

Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

Procedia PDF Downloads 429
2646 In Vitro Hepatoprotective and Anti-Hepatitis B Activitis of Cyperus rotundus Rhizome Fractions

Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari

Abstract:

Cyperus rotendus rhizomes are used as traditional medicine, including Ayurveda in chronic liver diseases and hepatitis B. We investigated the in vitro hepatoprotective and anti-hepatitis B virus (HBV) potential of Cyperus rotundus rhizome organic and aqueous fractions. Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells at 48 h. DCFH-toxicated cells were recovered to about 88% and 96%, upon treatment with n-butanol and aqueous fractions (200 g/ml), respectively compared to DCFH-only treated cells. Further, C. rotundus fractions were tested for anti-HBV activities by measuring the expression levels of viral antigens (HBsAg and HBeAg) in the HepG2.2.15 culture supernatants. At 48 h post-treatment, the ethyl acetate, n-butanol and aqueous fractions showed dose-dependent inhibition wherein at a higher dose (100 g/ml), HBsAg production was reduced to 60.27%, 46.87 and 42.76%, respectively. In a time-course study, HBsAg production was inhibited up to 50% and 40% by ethyl acetate and n-butanol fractions (100 g/ml), respectively on day 5. Three three active fractions were further subjected to time-dependent inhibition of HBeAg expression, an indirect measure of HBV active DNA replication. At day 5 post-treatment, ethyl acetate and n-butanol fractions downregulated HBV replication by 44.14% and 24.70%, respectively. In conclusion, our results showed very promising hepatoprotective and anti-HBV potential of C. rotendus tubers fractions in vitro. Our data could, therefore, provide the basis for the claimed traditional use of C. rotendus for jaundice and hepatitis.

Keywords: anti-hepatitis B, cyperus rotundus, hepatitis B virus, hepatoprotection

Procedia PDF Downloads 231
2645 Liposomal Antihelmintics in Parasitology

Authors: Nina Ivanova

Abstract:

More than one third of the population and animals are infected with parasitic helminths. It is especially difficult to cure the larval forms of parasites. The larvae of Hymenolepis nana invade the villi of the intestinal mucosa. Toxocara larvae can live in the liver, heart, lungs, brain, eyes, and pancreas. Commercial antiparasitic drugs cannot guarantee a 100% cure after a single course of treatment, because parasite larvae invade the villi of the intestinal mucosa and the anthelmintics do not reach and kill cestode larvae. The aim of this work was to conduct a study of liposomal antihelminthics on the laboratory animals under the certification received from the Committee on Bioethics and Deontology. It has been checked: 1) anthelmintic activity of the liposomal form of fenasal in experimental hymenolepidosis of white mice (larval stage - Hymenolepis nana). 2) anthelmintic activity of the liposomal form of albendazole in experimental toxocariasis of white mice (in the lungs at the stage of larval migration). Since some helminths cause hemolysis of erythrocytes as we used a mixture of polar lipids developed by us with antihemolytic activity to obtain liposomes Fenasal and albendazole were included in the liposome membrane in the ratio of anthelmintic: lipids 1:10. . The average size of liposomes was 180 nm, and the concentration of lipids in liposomes was 1%. The researches were carried out on white male mice who were infected with Hymenolepis Nana invasional eggs in a peroral way with a doze of 100 eggs per animal. On the 5th day after infection, a liposomal fenasal and commercial fenasal were administered orally for comparison. The animals were observed for 15 days. Before the introduction of liposomes and on the 3rd, 5th, 15th day after the administration of the drug, studies were carried out on the presence of helminths in the organs of animals. The liposomal fenasal, when administered orally, had an anthelmintic effect on Hymenolepis Nana cysticercoids at a dose of 25 mg/kg. The percentage of efficiency was 90.06, 91.36 96.85% on days 3, 5, 15, respectively. For comparison, the commercial activity was at a dose of 200 mg/ml, which is 8 times higher than the dose of liposomal fenasal. To evaluate the anthelmintic effect of the liposomal form of albendazole in experimental toxocariasis of white mice (toxascaris in the lungs at the stage of larval migration), studies were also carried out on white mice. The animals were infected with invasive eggs of Toxocara canis, orally, at a dose of 100 eggs per animal. On the 5th day after infection, the liposomal albendazole was administered orally. The efficacy of the study dosage form was determined by counting Larva mirgans larvae in the lungs. The results obtained showed that the liposomal albendazole had the greatest anthelmintic effect on Toxocara larvae at a dose of 2.0 mg/kg, which was 3.75 times less than the therapeutic one. At the same time, the percentage of efficiency was 93.75% on the 3rd day, and 98.66% on the 5th day.

Keywords: hymenolepis, Toxocara, larvae, liposomes

Procedia PDF Downloads 107
2644 Experimental Device to Test Corrosion Behavior of Materials in the Molten Salt Reactor Environment

Authors: Jana Petru, Marie Kudrnova

Abstract:

The use of technologies working with molten salts is conditioned by finding suitable construction materials that must meet several demanding criteria. In addition to temperature resistance, materials must also show corrosion resistance to salts; they must meet mechanical requirements and other requirements according to the area of use – for example, radiation resistance in Molten Salt Reactors. The present text describes an experimental device for studying the corrosion resistance of candidate materials in molten mixtures of salts and is a partial task of the international project ADAR, dealing with the evaluation of advanced nuclear reactors based on molten salts. The design of the device is based on a test exposure of Inconel 625 in the mixture of salts Hitec in a high temperature tube furnace. The result of the pre-exposure is, in addition to the metallographic evaluation of the behavior of material 625 in the mixture of nitrate salts, mainly a list of operational and construction problems that were essential for the construction of the new experimental equipment. The main output is a scheme of a newly designed gas-tight experimental apparatus capable of operating in an inert argon atmosphere, temperature up to 600 °C, pressure 3 bar, in the presence of a corrosive salt environment, with an exposure time of hundreds of hours. This device will enable the study of promising construction materials for nuclear energy.

Keywords: corrosion, experimental device, molten salt, steel

Procedia PDF Downloads 116
2643 Anti-Inflammatory Activity of Topical Anthocyanins by Complexation and Niosomal Encapsulation

Authors: Aroonsri Priprem, Sucharat Limsitthichaikoon, Suttasinee Thappasarapong

Abstract:

Anthocyanins are natural pigments with effective UV protection but their topical use could be limited due to their physicochemical characteristics. An attempt to overcome such limitations by complexation of 2 major anthocyanin-rich sources, C. ternatea, and Z. mays, for investigation on potential use as topical anti-inflammatory. Cell studies indicate no cytotoxicity of the anthocyanin complex (AC) up to 1 mg/ml tested in HaCaT and human forehead fibroblasts by MTT. Croton oil-induced ear edema in Wistar rats suggests an effective dose of 5 mg/cm2 of AC as a topical anti-inflammatory in comparison to 0.5 mg/cm2 of fluocinolone acetonide. Niosomal encapsulation of the AC significantly prolonged the anti-inflammatory activity particularly at 8 h after topical application (p = 0.0001). The AC was not cytotoxic and its anti-inflammatory and activity was dose-dependent and prolonged by niosomal encapsulation. It has also shown to promote collagen type 1 production in cell culture. Thus, AC could be a potential candidate for topical anti-inflammatory agent from natural resources.

Keywords: anthocyanin complex, ear edema, inflammation, niosomes, skin

Procedia PDF Downloads 322
2642 Potential Therapeutic Effect of Obestatin in Oral Mucositis

Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

Abstract:

Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

Procedia PDF Downloads 67
2641 Elucidation of Mechanism of Action of Antidepressant-Like Effect of Valeriana wallichii Maaliol Chemotype in Mice

Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

Abstract:

Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

Procedia PDF Downloads 293
2640 Bright Light Effects on the Concentration and Diffuse Attention Reaction Time, Tension, Angry, Fatigue and Alertness among Shift Workers

Authors: Mohammad Imani, JabraeilNasl Seraji, Abolfazl Zakerian

Abstract:

Background: Reaction time is the amount of time it takes to respond to a stimulus. In fact The time that passes between the introduction of a stimulus and the reaction by the subject to that stimulus. The aim of this interventional study is evaluation of bright light effects on concentration and diffuse attention reaction time, tension, angry, fatigue and alertness among shift workers. There are several incentives that can reduce the reaction time or added. Bright light as one of the environmental factors can reduce reaction time. Material &Method: This cross-sectional descriptive study was conducted in 1391, in 88 subjects (44 Fixed morning worker and 44 shift worker ) In a 24 h time (13-16-19-22-1-4-7-10) in an ordinary light situation after a randomly selected sample size calculation, concentration and diffuse attention test (reaction time) has been done. After intervention and using of bright light (4500lux), again reaction time test was done. After analyzing by ElISA method obtained data were analyzed by statistical software SPSS 19 and using T-test and ANOVA statistical analysis. Results: Between average of reaction time tests in ordinary light exposed to fixed morning workers and bright light exposed to shift worker, with 95% CI, (P>%5) there was no significant relationship. After the intervention and the use of bright light (4500 lux),between average of concentration and diffused attention reaction time tests in ordinary light exposure on the fixed morning workers and bright light exposure shift workers with 95% CI, (P<5%) there was significant relationship. Conclusion: In sometimes of 24 h during ordinary light exposure concentration and diffused attention reaction time has changed in shift workers. After intervention, during bright light (4500lux) exposure as a light shower, focused and diffuse attention reaction time, tension ,angry and fatigue decreased.

Keywords: bright light, reaction time, tension, angry, fatigue, alertness

Procedia PDF Downloads 378
2639 Positivity Rate of Person under Surveillance among Institut Jantung Negara’s Patients with Various Vaccination Statuses in the First Quarter of 2022, Malaysia

Authors: Mohd Izzat Md. Nor, Norfazlina Jaffar, Noor Zaitulakma Md. Zain, Nur Izyanti Mohd Suppian, Subhashini Balakrishnan, Geetha Kandavello

Abstract:

During the Coronavirus (COVID-19) pandemic, Malaysia has been focusing on building herd immunity by introducing vaccination programs into the community. Hospital Standard Operating Procedures (SOP) were developed to prevent inpatient transmission. Objective: In this study, we focus on the positivity rate of inpatient Person Under Surveillance (PUS) becoming COVID-19 positive and compare this to the National rate in order to see the outcomes of the patient who becomes COVID-19 positive in relation to their vaccination status. Methodology: This is a retrospective observational study carried out from 1 January until 30 March 2022 in Institut Jantung Negara (IJN). There were 5,255 patients admitted during the time of this study. Pre-admission Polymerase Chain Reaction (PCR) swab was done for all patients. Patients with positive PCR on pre-admission screening were excluded. The patient who had exposure to COVID-19-positive staff or patients during hospitalization was defined as PUS and were quarantined and monitored for potential COVID-19 infection. Their frequency and risk of exposure (WHO definition) were recorded. A repeat PCR swab was done for PUS patients that have clinical deterioration with or without COVID symptoms and on their last day of quarantine. The severity of COVID-19 infection was defined as category 1-5A. All patients' vaccination status was recorded, and they were divided into three groups: fully immunised, partially immunised, and unvaccinated. We analyzed the positivity rate of PUS patients becoming COVID-positive, outcomes, and correlation with the vaccination status. Result: Total inpatient PUS to patients and staff was 492; only 13 became positive, giving a positivity rate of 2.6%. Eight (62%) had multiple exposures. The majority, 8/13(72.7%), had a high-risk exposure, and the remaining 5 had medium-risk exposure. Four (30.8%) were boostered, 7(53.8%) were fully vaccinated, and 2(15.4%) were partial/unvaccinated. Eight patients were in categories 1-2, whilst 38% were in categories 3-5. Vaccination status did not correlate with COVID-19 Category (P=0.641). One (7.7%) patient died due to COVID-19 complications and sepsis. Conclusion: Within the first quarter of 2022, our institution's positivity rate (2.6%) is significantly lower than the country's (14.4%). High-risk exposure and multiple exposures to positive COVID-19 cases increased the risk of PUS becoming COVID-19 positive despite their underlying vaccination status.

Keywords: COVID-19, boostered, high risk, Malaysia, quarantine, vaccination status

Procedia PDF Downloads 85
2638 Protective Effect of Levetiracetam on Aggravation of Memory Impairment in Temporal Lobe Epilepsy by Phenytoin

Authors: Asher John Mohan, Krishna K. L.

Abstract:

Objectives: (1) To assess the extent of memory impairment induced by Phenytoin (PHT) at normal and reduced dose on temporal lobe epileptic mice. (2) To evaluate the protective effect of Levetiracetam (LEV) on aggravation of memory impairment in temporal lobe epileptic mice by PHT. Materials and Methods: Albino mice of either sex (n=36) were used for the study for a period of 64 days. Convulsions were induced by intraperitoneal administration of pilocarpine 280 mg/kg on every 6th day. Radial arm maze (RAM) was employed to evaluate the memory impairment activity on every 7th day. The anticonvulsant and memory impairment activity were assessed in PHT normal and reduced doses both alone and in combination with LEV. RAM error scores and convulsive scores were the parameters considered for this study. Brain acetylcholine esterase and glutamate were determined along with histopathological studies of frontal cortex. Results: Administration of PHT for 64 days on mice has shown aggravation of memory impairment activity on temporal lobe epileptic mice. Although the reduction in PHT dose was found to decrease the degree of memory impairment the same decreased the anticonvulsant potency. The combination with LEV not only brought about the correction of impaired memory but also replaced the loss of potency due to the reduction of the dose of the antiepileptic drug employed. These findings were confirmed with enzyme and neurotransmitter levels in addition to histopathological studies. Conclusion: This study thus builds a foundation in combining a nootropic anticonvulsant with an antiepileptic drug to curb the adverse effect of memory impairment associated with temporal lobe epilepsy. However further extensive research is a must for the practical incorporation of this approach into disease therapy.

Keywords: anti-epileptic drug, Phenytoin, memory impairment, Pilocarpine

Procedia PDF Downloads 306
2637 The Impact of Social Media Exposure on COVID- 19 Vaccine Hesitancy “A Comparative Study on the Public in Egypt and the United Arab Emirates”

Authors: Lamiaa Shehata

Abstract:

The current (COVID-19) pandemic is one of the international crises, and a lot of efforts have been directed toward the improvement of efficient vaccines, however vaccine hesitancy is one of the universal menaces that make the fulfillment of society immunity very hard. The World Health Organization acknowledges vaccine hesitancy as the society’s maximum risk to people's health protection, especially in little and moderate-revenue nations. Social media is strong in observing audience behaviors and evaluating the circulation, which would supply useful data for strategy makers. It has a significant function in spreading facts during the pandemic, it could assist to boost protective manners. The objective of this study is to determine the effects of social media exposure on vaccine hesitancy. Data were collected using a survey in a form of a structured questionnaire conducted during December 2021- January 2022 using convenient sampling techniques (680) in Egypt and the United Arab Emirates. The results revealed that there was a significant relationship between the high exposure to social media and the refusal of the Covid19 vaccine also, the percentage of the refusal of the vaccine is higher in Egypt, however, UAE forced people to take the vaccine. Furthermore, public attitudes toward COVID-19 vaccination vary from gender and region. In conclusion, policymakers must adjust their policies through the use of social media to immediate actions to vaccine-related news to support vaccination approval.

Keywords: COVID-19, hesitancy, social media, vaccine

Procedia PDF Downloads 128
2636 Exposure to Particulate Matter Taking Various Transportation Modes in Cebu City, Philippines

Authors: Mona Loraine M. Barabad, Duckshin Park, Michael E. Versoza

Abstract:

This study gives a comparison of the commuters’ exposure to particulate matter while taking different transportation mode (jeepney, motorcycle and taxi) in Cebu City, Philippines. A personal aerosol monitor (Sidepak AM510) was used for data collection; in addition, both temperature and humidity were also documented. Analysis was done and showed that Jeepney, which is the most commonly used mode in the country, has the highest PM collected having an average of 358.0μg/m^3, followed by the motorcycle with an average of 244.6 μg/m^3. The taxi recorded to have an average of 50.0 μg/m^3 and the lowest between the microenvironments sampled. The outcome was greatly significant to the traffic volume together with several factors that could possibly affect the result. However, due to the lack of time and resources, the data collected was limited. Further and thorough investigation should be implemented to provide more essential information regarding the subject.

Keywords: air quality, particulate matter, Philippines, transportation

Procedia PDF Downloads 358
2635 Larvicidal Activity of Azadirachtin and Essential Oils from Thymus capitatus against Prays oleae Bern (Lepidoptera, Yponomeutidae)

Authors: Imen Blibech, Mohiedine Ksantini, Mohamed Bouaziz

Abstract:

Prays oleae is a major insect of olive in the Mediterranean Region. In an effort to find effective and affordable ways of controlling this pest, larvicidal activity of essential oils from Tunisian Thymus capitatus were analyzed in comparison to Azadirachtin, a biologically active compound insecticide. The essential oils were extracted by hydrodistillation, and their chemical composition was determined by gas liquid-chromatography coupled with mass spectroscopy. The main components of chemical components were oxygenated monoterpenes (60.24%). The most abundant oxygenated monoterpenes were carvacrol (54.11%). Monoterpenes hydrocarbons were much more abundant and dominated by the o-cymene (16.68%). Both active compounds of Azadirachtin and Thymus capitatus oil extracts exhibited significant larvicidal activity against P. oleae with LC50 values 81.30 ppm and 52.49 ppm respectively. Dose-response relationships were established with almost 100% mortality when using the highest dose 100 ppm of T. capitatus oil extracts and 80 ppm of Azadirachtin. At the lowest dose (10 ppm), T. capitatus oil extracts and Azadirachtin caused 60% and 76% larval mortality in 48 hours respectively. The larval mortality rate greatly decreased with increases of the dilution of both oil extract compounds. Larval development duration appeared to be prolonged to about 12 days for larvae feeding on control diet. The maximum antifeedant activity was shown by both T. capitatus oil extract and Azadirachtin at LC90 values (47.5 and 50.1 ppm respectively). Tunisian T. capitatus oil extract used at low concentrations could be considered as eco-friendly promising insecticide similar to Azadirachtin that has significant potential for the biological control of P. oleae.

Keywords: Thymus capitatus, chemical composition, azadirachtin, larvicidal effects, antifeedant activity, Prays oleae

Procedia PDF Downloads 194
2634 Evaluation of Acetylcholinesterase, Glutathione S-Transferase and Catalase Activities in the Land Snail Helix aspersa Exposed to Thiamethoxam

Authors: Ait Hamlet Smina, Bensoltane Samira, Djekoun Mohamed, Berrebbah Houria

Abstract:

In Algeria, the use of insecticides and other phytosanitary products are considerably spreading with the development of agriculture. But, the analyses of the residues of pesticides are not systematically made. In this context, we estimated through an experimental study, the effect of a neonicotinoid insecticide, the thiamethoxam which is used as a commercial preparation on the land snail Helix aspersa. This snail is one of the most abundant gastropod in North-East Algeria. Little information is available in the literature concerning the study of the biochemical markers of mollusks which are exposed to insecticides and especially, thiamethoxam.In this work, adult snails Helix aspersa were used to estimate the effect of a neonicotinoid insecticide (thiamethoxam) on the acetylcholinesterase (AChE), glutathione S-transferase (GST) and catalase (CAT) activities in this gastropod after a treatment of 6 weeks. During this period, snails were exposed by ingestion and contact to fresh lettuce leaves which were soaked with an insecticide solution. The thiamethoxam test solutions were 0, 25, 50, 100 and 200 mg/L, which are lower or equal to the concentrations that are applied in field. The results showed that the enzymatic activities of AChE and GST and CAT increased significantly with a dose-dependent manner. These results confirmed the toxic effect of thiamethoxam on snails exposed to the lettuce contaminated with this neonicotinoid insecticide, likely to be used as biomarker of exposure, at first to thiamethoxam then to other insecticides belonging to the same chemical family, currently present in the environment.

Keywords: helix aspersa, insecticide, thiamethoxam, AChE, GST, CAT

Procedia PDF Downloads 444
2633 Effect of Fire Exposure on the Ultimate Strength of Loaded Columns

Authors: Hatem Hamdy Ghieth

Abstract:

In the recent time many fires happened in many skeleton buildings. The fire may be continues for a long time. This fire may cause a collapse of the building. This collapse may be happened due to the time of exposure to fire as well as the rate of the loading to the carrying elements. In this research a laboratory study for reinforced concrete columns under effect of fire with temperature reaches (650 ْ C) on the behavior of columns which loaded with axial load and with exposing to fire temperature only from all sides of columns. the main parameters of this study are level of load applying to the column, and the temperature applied to the fire, this temperatures was 500oC and 650oc. Nine concrete columns with dimensions 20x20x100 cms were casted one of these columns was tested to determine the ultimate load while the least were fired according to the experimental schedule.

Keywords: columns, fire duration, concrete strength, level of loading

Procedia PDF Downloads 433
2632 The Influence of Phosphate Fertilizers on Radiological Situation of Cultivated Lands: ²¹⁰Po, ²²⁶Ra, ²³²Th, ⁴⁰K and ¹³⁷Cs Concentrations in Soil

Authors: Grzegorz Szaciłowski, Marta Konop, Małgorzata Dymecka, Jakub Ośko

Abstract:

In 1996, the European Council Directive 96/29/EURATOM pointed phosphate fertilizers to have a potentially negative influence on the environment from the radiation protection point of view. Fertilizers along with irrigation and crop rotation were the milestones that allowed to increase agricultural productivity. Firstly based on natural materials such as compost, manure, fish processing waste, etc., and since the 19th century created synthetically, fertilizers caused a boom in crop yield and helped to propel global food production, especially after World War II. In this work the concentrations of ²¹⁰Po, ²²⁶Ra, ²³²Th, ⁴⁰K, and ¹³⁷Cs in selected fertilizers and soil samples were determined. The results were used to calculate the annual addition of natural radionuclides and increment of the external radiation exposure caused by the use of studied fertilizers. Soils intended for different types of crops were sampled in early spring when no vegetation had occurred yet. Analysed fertilizers were those with which the soil was previously fertilized. For gamma radionuclides, a high purity germanium detector GX3520 from Canberra was used. The polonium concentration was determined by radiochemical separation followed by measurement by means of alpha spectrometry. The spectrometer used in this study was equipped with 450 cm² PIPS detector from Canberra. Obtained results showed significant differences in radionuclide composition between phosphate and nitrogenous fertilizers (e.g. the radium equivalent activity for phosphate fertilizer was 207.7 Bq/kg in comparison to <5.6 Bq/kg for nitrogenous fertilizer). The calculated increase of external radiation exposure due to use of phosphate fertilizer ranged between 3.4 and 5.4 nG/h, which represents up to 10% of the polish average outdoor exposure due to terrestrial gamma radiation (45 nGy/h).

Keywords: ²¹⁰Po, alpha spectrometry, exposure, gamma spectrometry, phosphate fertilizer, soil

Procedia PDF Downloads 292
2631 Craving Intensity Measurements in Opiate Addicts to Objectify the Opioid Substitution Therapy Dose and Reduce the Relapse Risk

Authors: Igna Brajevic-Gizdic, Magda Pletikosa Pavić

Abstract:

Introduction: Research in opiate addiction is increasingly indicating the importance of substitution therapy in opiate addicts. Opiate addiction is a chronic relapsing disease that includes craving as a criterion. Craving has been considered a predictor of a relapse, which is defined as a strong desire with an excessive need to take a substance. The study aimed to measure the intensity of craving using the VAS (visual analog scale) in opioid addicts taking Opioid Substitution Therapy (OST). Method: The total sample compromised of 30 participants in outpatient treatment. Two groups of opiate addicts were considered: Methadone-maintenance and buprenorphine-maintenance addicts. The participants completed the survey questionnaire during the outpatient treatment. Results: The results indicated high levels of cravings in patients during the treatment of OST, which is considered an important destabilization factor in abstinence. Thus, the use of methadone/buprenorphine dose should be considered. Conclusion: These findings provided an objective measurement of methadone /buprenorphine dosage and therapy options. The underdoes of OST can put patients at high risk of relapse, resulting in high levels of craving. Thus, when determining the therapeutic dose of OST, it is crucial to consider patients' cravings. This would achieve stabilization more quickly and avoid relapse in abstinence. Subjective physician assessment and patients' statement are the main criteria to determine OST dosage. Future studies should use larger sample sizes and focus on the importance of intensity craving measurement on OST to objectify methadone /buprenorphine dosage.

Keywords: buprenorphine, craving, heroin addicts, methadone, OST

Procedia PDF Downloads 82
2630 Biosorption of Fluoride from Aqueous Solutions by Tinospora Cordifolia Leaves

Authors: Srinivasulu Dasaiah, Kalyan Yakkala, Gangadhar Battala, Pavan Kumar Pindi, Ramakrishna Naidu Gurijala

Abstract:

Tinospora cordifolia leaves biomass used for the removal fluoride from aqueous solutions. Batch biosorption technique was applied, pH, contact time, biosorbent dose and initial fluoride concentration was studied. The Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) techniques used to study the surface characteristics and the presence of chemical functional groups on the biosorbent. Biosorption isotherm models and kinetic models were applied to understand the sorption mechanism. Results revealed that pH, contact time, biosorbent dose and initial fluoride concentration played a significant effect on fluoride removal from aqueous solutions. The developed biosorbent derived from Tinospora cordifolia leaves biomass found to be a low-cost biosorbent and could be used for the effective removal of fluoride in synthetic as well as real water samples.

Keywords: biosorption, contact time, fluoride, isotherms

Procedia PDF Downloads 173
2629 Pharmacodynamic Interaction between Tamsulosin and Finasteride Treatment on Induced Benign Prostate Hyperplasia in Mice by Using Chou-Talalay Method

Authors: Firas Rashad Al-Samarai

Abstract:

Introduction: Benign prostatic hyperplasia (BPH) is a common condition as men get older. An enlarged prostate gland can cause uncomfortable urinary symptoms, such as blocking the flow of urine out of the bladder. It can also cause bladder, urinary tract, or kidney problems. Objective: to evaluate the efficacy and interaction of tamsulosin with finasteride treatment on induced benign prostate hyperplasia (BPH) in mice. Methods: BPH was induced by subcutaneous injection of testosterone propionate (20 mg/kg) for 30 days. Eighty-five mice were divided into five groups. The first group (G1): twenty-five mice induced BPH treated with tamsulosin orally and divided into five equal subgroups with doses (0.017, 0.052, 0.087, 0. 123, and 0.158) mg/kg, the second group (G2): twenty-five mice induced BPH treated with finasteride orally and divided into five equal subgroups with doses (0.175, 0.527, 0.878, 1.23, and 1.580) mg/kg. the third group (G3): twenty-five mice induced BPH treated with a combination of tamsulosin with finasteride orally, and divided into five equal subgroups with doses (0.0085, 0.0875), (0.026, 0.2635), (0.0435, 0.439) , (0.0615, 0.615) and ( 0.079 , 0.790 ) mg/kg respectively. Fourth group (G4): five mice induced BPH and treated distilled water. Fifth group (G5): five mice were not inducing BPH and without any treatment. Results: The results showed a gradual significant increase in prostate weight % and prostate index % Inhibitions until reached saturation in the last two doses of tamsulosin, finasteride, and combination groups, the maximum effective dose of tamsulosin and finasteride were (0.156) and (1.495) mg/kg respectively. Moreover, the effective dose of the combination (tamsulosin and finasteride) was estimated (0.06876, 0.6876) mg/kg, respectively, as well as the type of interaction was synergism and the value of the combination index was 0.046. Conclusions: We concluded that the combination of tamsulosin with finasteride showed a synergistic effect in BPH treatment by minimizing the side effect of each drug as s result of decreasing the dose of each one.

Keywords: Tamsulosin, Finasteride, combination, BPH

Procedia PDF Downloads 73
2628 Insecticide Efficacy against Jassids in Egg Plants

Authors: Zunnu Raen Akhtar, Farhan Ali, Muhammad Saeed-Ur-Rehman

Abstract:

Jassids are considered as serious sucking pests in eggplants. Jassids can be controlled using imidacloprid, but it can also result in non-target ecological impacts on eco-system. It can also result in reduced population of predators of jassids in the field. An experiment was conducted on jassids, Amrasca sp. reared on eggplant leaves were treated with insecticide imidacloprid at lower, recommended and higher doses including 1L, 2L, 3L respectively. 3rd instar larvae and adults of jassids were exposed to lower, recommended, higher doses. Mortality tests were repeated three times for each dose and insect growth stage. Imidacloprid was sprayed on the leaves followed by drying. Data was recorded for 4, 8, 12, 16, 20, 24 hours after spraying insecticide on the leaves. Results showed that higher mortality was observed in higher and recommended doses, while slow mortality was observed in the case of lower dose. It can be asserted that higher and recommended doses causing immediate mortality of insects are better to control Amrasca sp. in the field, it will not cause immediate resistance development in insects against imidacloprid.

Keywords: Amrasca sp., imidacloprid, egg plant, efficacy

Procedia PDF Downloads 218
2627 Methylprednisolone Injection Did Not Inhibit Anti-Hbs Response Following Hepatitis B Vaccination in Mice

Authors: P. O. Ughachukwu, P. O. Okonkwo, P. C. Unekwe, J. O. Ogamba

Abstract:

Background: The prevalence of hepatitis B viral infection is high worldwide with liver cirrhosis and hepatocellular carcinoma as important complications. Cases of poor antibody response to hepatitis B vaccination abound. Immunosuppression, especially from glucocorticoids, is often cited as a cause of poor antibody response and there are documented evidences of irrational administration of glucocorticoids to children and adults. The study was, therefore, designed to find out if administration of glucocorticoids affects immune response to vaccination against hepatitis B in mice. Methods: Mice of both sexes were randomly divided into 2 groups. Daily intramuscular methylprednisolone injections, (15 mg kg-1), were given to the test group while sterile deionized water (0.1ml) was given to control mice for 30 days. On day 6 all mice were given 2 μg (0.1ml) hepatitis B vaccine and a booster dose on day 27. On day 34, blood samples were collected and analyzed for anti-HBs titres using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was done using Graph Pad Prism 5.0 and the results taken as statistically significant at p value < 0.05. Results: There were positive serum anti-HBs responses in all mice groups but the differences in titres were not statistically significant. Conclusions: At the dosages and length of exposure used in this study, methylprednisolone injection did not significantly inhibit anti-HBs response in mice following immunization against hepatitis B virus. By extrapolation, methylprednisolone, when used in the usual clinical doses and duration of therapy, is not likely to inhibit immune response to hepatitis B vaccinations in man.

Keywords: anti-HBs, hepatitis B vaccine, immune response, methylprednisolone, mice

Procedia PDF Downloads 319
2626 Physiological and Reproductive Changes in Honey Bee Female Castes Following Direct Colony Exposure to Pesticides

Authors: Valizadeh Gever Bita, Joel Caren, Louisa Huand, Yu-Cheng Zhu, Esmaeil Amiri

Abstract:

Within a honey bee colony, queen is the sole reproducer of fertilized eggs, while queens are safeguarded by worker bees, trophallactic behavior and food sharing activities could expose them to agrochemicals. Here, we assessed the effects of three widely used pesticides—Acephate, Bifenthrin, and Chlorantraniliprole— on worker bees, to investigate indirect effects on the physiology and reproductive traits of queens as well as the eggs they produce. Using RT-qPCR we measured the expression of several detoxification and immune genes in adult worker bees, queens, and freshly laid eggs after pesticide exposure. These analyses aimed to elucidate the physiological changes in queens and potential transgenerational effects. While no significant changes in reproductive traits were observed following Chlorantraniliprole and Bifenthrin exposure, Acephate caused adverse effects on egg size, egg-laying activity, and queen weight. The expression of detoxification, immune and antioxidant-related genes in workers, queens and freshly laid eggs changed over time in response to these pesticides. The results of this investigation revealed that pesticides can cause negative impact on queen physiology and reproduction indirectly through their effects on exposed worker bees. These effects can potentially extend to the next generation of honey bees.

Keywords: apis mellifera, egg laying, detoxification enzymes, gene expression, honey bee queen

Procedia PDF Downloads 58
2625 Effect of Amlodipine on Dichlorvos-Induced Seizure in Mice

Authors: Omid Ghollipoor Bashiri, Farzam Hatefi

Abstract:

Dichlorvos a synthetic organophosphate poisons are used as insecticide. These toxins can be used insecticides in agriculture and medicine for destruction and/or eradication of ectoparasites of animals. Studies have shown that Dichlorvos creation seizure effects in different animals. Amlodipine, dihydropyridine calcium channel blockers, widely used for treatment of cardiovascular diseases. Studies have shown that the calcium channel blockers are anticonvulsant effects in different animal models. The aim of this study was to determine the effect of Amlodipine on Dichlorvos-induced seizures in mice. In this experiment, the animals were received different doses of Amlodipine (2.5, 5, 10, 20 and 40 mg/ kg b.wt.) intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg/kg b.wt). After Dichlorvos injection, clonic and tonic seizures, and finally was the fate was investigated. Results showed that Amlodipine dose-dependently reduced the severity of Dichlorvos-induced seizures, so that Amlodipine at a dose of 5mg (The lowest, p<0.05) and 40 mg/kg b.wt. (The highest, p<0.001) which had anticonvulsant effects. The anticonvulsant activity of Amlodipine suggests that possibly due to the antagonistic effect on voltage-dependent calcium channel.

Keywords: dichlorvos, amlodipine, seizures, mice

Procedia PDF Downloads 300
2624 Observational Study of Ionising Radiation Exposure in Orthopaedic Theatre

Authors: Adam Aboalkaz, Rana Shamoon, Duncan Meikle, James Lewis

Abstract:

Background and aims: In orthopaedic theatres, radiological screening during operations is a commonly used and useful technique to visualise and guide the operating surgeon. Within any theatre using ionising radiation, it is imperative that the use of protective equipment and the wearing of a dosimeter at all times. 1. To assess compliance with use of protective equipment during orthopaedic procedures involving ionising radiation. 2. To assess the radiation risk knowledge of staff members regularly present in an orthopaedic theatre of a national major trauma centre, in accordance to the ionising radiation regulation (2000) guidelines. Method: We conducted an Observational study of 21 operations at the University Hospital of Wales, which is a major trauma centre, recording the compliance with use of protective equipment (lead aprons and thyroid shields) and dosimeters. The observations were performed sporadically over a two week period to ensure that all staff in monitored operating theatres were not aware of the ongoing study, as to avoid bias. A questionnaire testing the knowledge of trainees and staff within the orthopaedic department was given following completion of the initial phase of the study, with 19 responses. The questions were based on knowledge of ionising radiation exposure and monitoring. The questions also tested the general staff knowledge of what equipment should be worn and where to locate such equipment. Results: This study found that only 25% of staff members were wearing thyroid protectors when less than 1 meter from the radiation source and only 50% were wearing appropriate lead aprons whilst in this same vicinity. The study also showed that 0% of all staff members used a dosimeter whilst in an area of radiation exposure. From the distributed questionnaires, only 40% of staff understood where to stand whilst radiation was being used, and only 25% of staff knew where to find protective equipment. Conclusion: Overall our audit showed poor compliance with regards to the National and local policies, due to lack of awareness of the policy and lack of basic ionising radiation exposure knowledge. It was evident from the observational study and questionnaire that staff were not fully aware of what equipment should be worn, where to find such equipment and did not appreciate that the distance from the ionising radiation source altered its exposure effect. This lack of knowledge may affect the staff health and safety after long term exposure. Changes to clinical practice: From the outcome of this study, we managed to drastically increase awareness of ionising radiation within the orthopaedic department. A mandatory teaching session on the safety of ionising radiation has been incorporated into the orthopaedic induction week for all staff. The dosimeters have been moved to a visible location within the trauma operating theatre and all staff made aware of where to find protective equipment.

Keywords: audit, ionising radiation, observational study, protection

Procedia PDF Downloads 252
2623 Rabies Surveillance Data Analysis in Addis Ababa, Ethiopia during 2012/13: Retrospective Cross Sectional Study

Authors: Fantu Lombamo Untiso, Sylvia Murphy, Emily Pieracci

Abstract:

Background: Rabies is a highly fatal viral disease of all warm-blooded animals including human globally. However, effective rabies control program still remains to be a reality and needs to be strengthened. Objective: Reviewing of recorded data and analyzing it to generate information on the status of rabies in Addis Ababa in the year 2012/13. Methods: A retrospective data were used from the Ethiopian Public Health Institute rabies case record book registered in the year 2012/13. Results: Among 1357 suspected rabid animals clinically examined; only 8.84% were positive for rabies. Out of 216 animal brains investigated in the laboratory with Fluorescent Antibody Technique, 55.5% were confirmed rabies positive. Among the laboratory confirmed positive rabies cases, high percentage of the animals came from Yeka (20%) and lower number from Kirkos subcity (3.3%). Out of 1149 humans who came to the institute seeking anti-rabies post-exposure prophylaxis, 85.65% and 7.87% of them were exposed to suspected dogs and cats respectively. 3 human deaths due to rabies were reported in the year after exposure to dog bite of unknown vaccination status. Conclusion: The principal vector of rabies in Addis Ababa is dog. Effective rabies management and control based on confirmed cases and mass-immunization and control of stray dog populations is recommended.

Keywords: Addis Ababa, exposure, rabies, surveillance

Procedia PDF Downloads 172
2622 Targeting Tumour Survival and Angiogenic Migration after Radiosensitization with an Estrone Analogue in an in vitro Bone Metastasis Model

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

Abstract:

Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 154
2621 A Systematic Review for the Association between Active Smoking and Latent Tuberculosis Infection

Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh

Abstract:

Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.

Keywords: latent tuberculosis infection, systematic review, active smoking, model

Procedia PDF Downloads 251