Search results for: cardiac toxicity

Authors: Ledi Neçaj

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Objectives: The target of this paper is (1) to explain objectively physical activity model throughout three chronic cardiopulmonary conditions, and (2) to study the connection among physical activity dimensions with disease severity, self-reported physical and emotional functioning, and exercise performance. Material and Methods: This is a cross-sectional study of patients in their domestic environment. Patients with cardiopulmonary diseases were: chronic obstructive pulmonary disease (COPD), (n-63), coronary heart failure (n=60), and patients with implantable cardioverter defibrillator (n=60). Main results measures: Seven ambulatory physical activity dimensions (total steps, percentage time active, percentage time ambulating at low, medium, and hard intensity, maximum cadence for 30 non-stop minutes, and peak performance) have been measured with an accelerometer. Results: Subjects with COPD had the lowest amount of ambulatory physical activity compared with topics with coronary heart failure and cardiac dysrhythmias (all 7 interest dimensions, P<.05); total step counts have been: 5319 as opposed to 7464 as opposed to 9570, respectively. Six-minute walk distance becomes correlated (r=.44-.65, P<.01) with all physical activity dimensions inside the COPD pattern, the most powerful correlations being with total steps and peak performance. In topics with cardiac impairment, maximal oxygen intake had the most effective small to slight correlations with five of the physical activity dimensions (r=.22-.40, P<.05). In contrast, correlations among 6-minute walk test distance and physical activity have been higher (r=.48-.61, P<.01) albeit in a smaller pattern of most effective patients with coronary heart failure. For all three samples, self-reported physical and mental health functioning, age, frame mass index, airflow obstruction, and ejection fraction had both exceptionally small and no significant correlations with physical activity. Conclusions: Findings from this study present a profitable benchmark of physical activity patterns in individuals with cardiopulmonary diseases for comparison with future studies. All seven dimensions of ambulatory physical activity have disfavor between subjects with COPD, heart failure, and cardiac dysrhythmias. Depending on the research or clinical goal, the use of one dimension, such as total steps, may be sufficient. Although physical activity had high correlations with performance on a six-minute walk test relative to other variables, accelerometers-based physical activity monitoring provides unique, important information about real-world behavior in patients with cardiopulmonary not already captured with existing measures.

Keywords: ambulatory physical activity, walking, monitoring, COPD, heart failure, implantable defibrillator, exercise performance

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: Vadim A. Kuznetsov, Anna M. Soldatova, Tatyana N. Enina, Elena A. Gorbatenko, Dmitrii V. Krinochkin

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The aim of the study was to evaluate potential parameters related with super-response to CRT. Methods: 60 CRT patients (mean age 54.3 ± 9.8 years; 80% men) with congestive heart failure (CHF) II-IV NYHA functional class, left ventricular ejection fraction < 35% were enrolled. At baseline, 1 month, 3 months and each 6 months after implantation clinical, electrocardiographic and echocardiographic parameters, NT-proBNP level were evaluated. According to the best decrease of left ventricular end-systolic volume (LVESV) (mean follow-up period 33.7 ± 15.1 months) patients were classified as super-responders (SR) (n=28; reduction in LVESV ≥ 30%) and non-SR (n=32; reduction in LVESV < 30%). Results: At baseline groups differed in age (58.1 ± 5.8 years in SR vs 50.8 ± 11.4 years in non-SR; p=0.003), gender (female gender 32.1% vs 9.4% respectively; p=0.028), width of QRS complex (157.6 ± 40.6 ms in SR vs 137.6 ± 33.9 ms in non-SR; p=0.044). Percentage of LBBB was equal between groups (75% in SR vs 59.4% in non-SR; p=0.274). All parameters of mechanical dyssynchrony were higher in SR, but only difference in left ventricular pre-ejection period (LVPEP) was statistically significant (153.0 ± 35.9 ms vs. 129.3 ± 28.7 ms p=0.032). NT-proBNP level was lower in SR (1581 ± 1369 pg/ml vs 3024 ± 2431 pg/ml; p=0.006). The survival rates were 100% in SR and 90.6% in non-SR (log-rank test P=0.002). Multiple logistic regression analysis showed that LVPEP (HR 1.024; 95% CI 1.004–1.044; P = 0.017), baseline NT-proBNP level (HR 0.628; 95% CI 0.414–0.953; P=0.029) and age at baseline (HR 1.094; 95% CI 1.009-1.168; P=0.30) were independent predictors for CRT super-response. ROC curve analysis demonstrated sensitivity 71.9% and specificity 82.1% (AUC=0.827; p < 0.001) of this model in prediction of super-response to CRT. Conclusion: Super-response to CRT is associated with better survival in long-term period. Presence of LBBB was not associated with super-response. LVPEP, NT-proBNP level, and age at baseline can be used as independent predictors of CRT super-response.

Keywords: cardiac resynchronisation therapy, superresponse, congestive heart failure, left bundle branch block

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Authors: Melanie Ostermann, Eivind Birkeland, Ying Xue, Alexander Sauter, Mihaela R. Cimpan

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Background: New reliable and robust techniques to assess biological effects of nanomaterials (NMs) in vitro are needed to speed up safety analysis and to identify key physicochemical parameters of NMs, which are responsible for their acute cytotoxicity. The central aim of this study was to validate and evaluate the applicability and reliability of an impedance-based flow cytometry (IFC) technique for the high-throughput screening of NMs. Methods: Eight inorganic NMs from the European Commission Joint Research Centre Repository were used: NM-302 and NM-300k (Ag: 200 nm rods and 16.7 nm spheres, respectively), NM-200 and NM- 203 (SiO₂: 18.3 nm and 24.7 nm amorphous, respectively), NM-100 and NM-101 (TiO₂: 100 nm and 6 nm anatase, respectively), and NM-110 and NM-111 (ZnO: 147 nm and 141 nm, respectively). The aim was to assess the biological effects of these materials on human monoblastoid (U937) cells. Dispersions of NMs were prepared as described in the NANOGENOTOX dispersion protocol and cells were exposed to NMs at relevant concentrations (2, 10, 20, 50, and 100 µg/mL) for 24 hrs. The change in electrical impedance was measured at 0.5, 2, 6, and 12 MHz using the IFC AmphaZ30 (Amphasys AG, Switzerland). A traditional toxicity assay, Trypan Blue Dye Exclusion assay, and dark-field microscopy were used to validate the IFC method. Results: Spherical Ag particles (NM-300K) showed the highest toxic effect on U937 cells followed by ZnO (NM-111 ≥ NM-110) particles. Silica particles were moderate to non-toxic at all used concentrations under these conditions. A higher toxic effect was seen with smaller sized TiO2 particles (NM-101) compared to their larger analogues (NM-100). No interferences between the IFC and the used NMs were seen. Uptake and internalization of NMs were observed after 24 hours exposure, confirming actual NM-cell interactions. Conclusion: Results collected with the IFC demonstrate the applicability of this method for rapid nanotoxicity assessment, which proved to be less prone to nano-related interference issues compared to some traditional toxicity assays. Furthermore, this label-free and novel technique shows good potential for up-scaling in directions of an automated high-throughput screening and for future NM toxicity assessment. This work was supported by the EC FP7 NANoREG (Grant Agreement NMP4-LA-2013-310584), the Research Council of Norway, project NorNANoREG (239199/O70), the EuroNanoMed II 'GEMN' project (246672), and the UH-Nett Vest project.

Keywords: cytotoxicity, high-throughput, impedance, nanomaterials

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Ildiko Fekete-Kertesz, Jade Chaker, Sylvain Berthelot, Viktoria Feigl, Monika Molnar, Lidia Favier

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There has been growing concern about emerging micropollutants in recent years, because of the possible environmental and health risk posed by these substances, which are released into the environment as a consequence of anthropogenic activities. Among them pharmaceuticals are currently not considered under water quality regulations; however, their potential effect on the environment have become more frequent in recent years. Due to the fact that these compounds can be detected in natural water matrices, it can be concluded, that the currently applied water treatment processes are not efficient enough for their effective elimination. To date, advanced oxidation processes (AOPs) are considered as highly competitive water treatment technologies for the removal of those organic micropollutants not treatable by conventional techniques due to their high chemical stability and/or low biodegradability. AOPs such as (photo)chemical oxidation and heterogeneous photocatalysis have proven their potential in degrading harmful organic compounds from aqueous matrices. However, some of these technologies generate reaction by-products, which can even be more toxic to aquatic organisms than the parent compounds. Thus, target compound removal does not necessarily result in the removal of toxicity. Therefore, to evaluate process efficiency the determination of the toxicity and ecotoxicity of the reaction intermediates is crucial to estimate the environmental risk of such techniques. In this context, the present study investigates the effectiveness of TiO2 assisted photodegradation for the removal of emerging water contaminants. Two drugs named losartan (used in high blood pressure medication) and levetiracetam (used to treat epilepsy) were considered in this work. The photocatalytic reactions were carried out with a commercial catalyst usually employed in photocatalysis. Moreover, the toxicity of the by-products generated during the process was assessed with various ecotoxicological methods applying aquatic test organisms from different trophic levels. A series of experiments were performed to evaluate the toxicity of untreated and treated solutions applying the Aliivibrio fischeri bioluminescence inhibition test, the Tetrahymena pyriformis proliferation inhibition test, the Daphnia magna lethality and immobilization tests and the Lemna minor growth inhibition test. The applied ecotoxicological methodology indicated sensitively the toxic effects of the treated and untreated water samples, hence the applied test battery is suitable for the ecotoxicological characterization of TiO2 based photocatalytic water treatment technologies and the indication of the formation of toxic by-products from the parent chemical compounds. Obtained results clearly showed that the TiO2 assisted photodegradation was more efficient in the elimination of losartan than levetiracetam. It was also observed that the treated levetiracetam solutions had more severe effect on the applied test organisms. A possible explanation would be the production of levetiracetam by-products, which are more toxic than the parent compound. The increased toxicity and the risk of formation of toxic metabolites represent one possible limitation to the implementation of photocatalytic treatment using TiO2 for the removal of losartan and levetiracetam. Our results proved that, the battery of ecotoxicity tests used in this work can be a promising investigation tool for the environmental risk assessment of photocatalytic processes.

Keywords: aquatic micropollutants, ecotoxicology, nano titanium dioxide, photocatalysis, water treatment

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Authors: Asif Husain, Shah Alam Khan

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Coumarins and flavones are oxygen containing heterocyclic compounds which are present in various biologically active compounds. Both the heterocyclic rings are associated with diverse biological actions, therefore considered as an important scaffold for the design of molecules of pharmaceutical interest. Aim: To synthesize and evaluate the in vivo anti-inflammatory activity of few coumrain and flavone derivatives containing 1,4 dioxane ring system. Materials and methods: Coumarin derivatives (3a-d) were synthesized by reacting 7,8 dihydroxy coumarin (2a) and its 4-methyl derivative (2b) with epichlorohydrin/ethylene dibromide. The flavone derivatives (10a-d) were prepared by using quercetin and 3,4 dihydroxy flavones. Compounds of both the series were also evaluated for their anti-inflammatory, analgesic activity and ulcerogenicity in animal models by reported methods. Results and Discussion: The structures of all newly synthesized compounds were confirmed with the help of IR, 1H NMR, 13C NMR and Mass spectral studies. Elemental analyses data for each element analyzed (C, H, N) was found to be within acceptable range of ±0.4 %. Flavone derivatives, but in particular quercetin containing 1,4 dioxane ring system (10d) showed better anti-inflammatory and analgesic activity along with reduced gastrointestinal toxicity as compared to other synthesized compounds. The results of anti-inflammatory and analgesic activities of both the series are comparable with the positive control, diclofenac. Conclusion: Compound 10d, a quercetin derivative, emerged as a lead molecule which exhibited potent anti-inflammatory and analgesic activity with significant reduced gastric toxicity.

Keywords: analgesic, anti-inflammatory, 1, 4 dioxane, coumarin, flavone

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Authors: Hajar Hosseini Khorami

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Porphyrins are organic, aromatic compounds found in heme, cytochrome, cobalamin, chlorophyll , and many other natural products with essential roles in biological processes that their cationic forms have been used as groups of favorable non-viral vectors recently. Cationic porphyrins are self-chromogenic reagents with a high capacity for modifications, great interaction with DNA and protection of DNA from nuclease during delivery of it into a cell with low toxicity. In order to have high efficient gene transfection into the cell while causing low toxicity, genetically manipulations of the non-viral vector, cationic porphyrin, would be useful. In this study newly modified cationic porphyrin derivative, 5, 10-dihexyl-15, 20bis (N-methyl-4-pyridyl) porphyrin was applied. Cytotoxicity of synthesized cationic porphyrin on Chinese Hamster Ovarian (CHO) cells was evaluated by using MTT assay. This cationic derivative is dose-dependent, with low cytotoxicity at the ranges from 100 μM to 0.01μM. It was uptake by cells at high concentration. Using direct non-viral gene transfection method and different concentration of cationic porphyrin were tested on transfection of CHO cells by applying derived transfection reagent with X-tremeGENE HP DNA as a positive control. However, no transfection observed by porphyrin derivative and the parameters tested except for positive control. Results of this study suggested that applying different protocol, and also trying other concentration of cationic porphyrins and DNA for forming a strong complex would increase the possibility of efficient gene transfection by using cationic porphyrins.

Keywords: cationic porphyrins, gene delivery, non-viral vectors, transfection reagents

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Ahmad Abdi, M. Golzadeh Gangeraj, Alireza Barari, S. Shirali, S. Amini

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Aims: Diabetes is one of the common metabolic diseases in the world that has the dire adverse effects such as nephropathy, retinopathy and cardiovascular problems. Pharmaceutical and non-pharmaceutical strategies for control and treatment of diabetes are provided. Exercise and nutrition as non-drug strategies for the prevention and control of diabetes are considered. Exercises may increase oxidative stress and myocardium injury, thus it is necessary to take nutrition strategies to help diabetic athletes. Methods: This study was a semi-experimental research. Therefore, 24 men with type 2 diabetes were selected and randomly divided in four groups (1. control, 2. saffron extract, 3. aerobic exercises, 4. compound aerobic exercises and saffron extract). Saffron extract with 100 mg/day was used. Aerobic exercises, three days a week, for eight weeks, with 55-70% of maximum heart rate were performed. At the end, levels of Heart-type fatty acid-binding protein (HFABP) and Troponin T were measured. Data were analyzed by Paired t, One-way ANOVA and Tukey tests. Results: The serum Troponin T increased significantly in saffron extract, aerobic exercises and compound saffron extract -aerobic exercises in type 2 diabetic men(P=0.024, P =0.013, P=0.005 respectively). Saffron extract consumption (100 mg/day) and aerobic exercises did not significantly influence the serum HFABP (P =0.365, P =0.188 respectively). But serum HFABP decreased significantly in compound saffron extract -aerobic exercises group (P =0.003). Conclusions: Raised cardiac Troponin T and HFABP concentration accepted as the standard biochemical markers for the diagnosis of cardiac injury. Saffron intake may beneficially protect the myocardium from injuries. Compound saffron extract -aerobic exercises can decrease levels of Troponin T and HFABP in men with type 2 diabetes.

Keywords: Saffron, aerobic exercises, type 2 diabetes, HFABP, troponin T

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Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

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Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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Authors: Magdy Abouzeid, Nancy Abouzeid, Afaf Salem

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Background: The elite child athletes are one who has superior athletic talent. Monofin (a single surface swim fin) swimming already proved to be the most efficient method of swimming for human being. This is a novel descriptive study examining myocardial function indices in prepubertal monofin children. The aim of the present study was to determine the influence of long-term monofin training (LTMT), 36 weeks, 6 times per week, 90 min per unit on Myocardial function adaptation in elite child monofin athletes. Methods: 14 elite monofin children aged 11.95 years (± 1.09 yr) took part for (LTMT). All subjects underwent two-dimension, M-mode, and Doppler echocardiography before and after training to evaluate cardiac dimensions and function; septal and posterior wall thickness. Statistical methods of SPSS, means ± SD and paired t test, % of improvement were used. Findings: There was significant difference (p<0.01) and % improvement for all echocardiography parameter after (LTMT). Inter ventricular septal thickness in diastole and in systole increased by 27.9 % and 42.75 %. Left ventricular end systolic dimension and diastole increased by 16.81 % and 42.7 % respectively. Posterior wall thickness in systole very highly increased by 283.3 % and in diastole increased by 51.78 %. Left ventricular mass in diastole and in systole increased by 44.8 % and 40.1 % respectively. Stroke volume (SV) and resting heart rate (HR) significant changed (sv) 25 %, (HR) 14.7 %. Interpretation: the unique swim fin tool and create propulsion and overcome resistance. Further researches are needed to determine the effects of monofin training on right ventricular in child athletes.

Keywords: prepubertal, monofin training, heart athlete's, elite child athlete, echocardiography

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Authors: Zouhair Haddi, Stephane Delliaux, Jean-Francois Pons, Ismail Kechaf, Jean-Claude De Haro, Mustapha Ouladsine

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Atrial fibrillation (AF) has been considered as the most common cardiac arrhythmia, and a major public health burden associated with significant morbidity and mortality. Nowadays, telemedical approaches targeting cardiac outpatients situate AF among the most challenged medical issues. The automatic, early, and fast AF detection is still a major concern for the healthcare professional. Several algorithms based on univariate analysis have been developed to detect atrial fibrillation. However, the published results do not show satisfactory classification accuracy. This work was aimed at resolving this shortcoming by proposing multivariate data analysis methods for automatic AF detection. Four publicly-accessible sets of clinical data (AF Termination Challenge Database, MIT-BIH AF, Normal Sinus Rhythm RR Interval Database, and MIT-BIH Normal Sinus Rhythm Databases) were used for assessment. All time series were segmented in 1 min RR intervals window and then four specific features were calculated. Two pattern recognition methods, i.e., Principal Component Analysis (PCA) and Learning Vector Quantization (LVQ) neural network were used to develop classification models. PCA, as a feature reduction method, was employed to find important features to discriminate between AF and Normal Sinus Rhythm. Despite its very simple structure, the results show that the LVQ model performs better on the analyzed databases than do existing algorithms, with high sensitivity and specificity (99.19% and 99.39%, respectively). The proposed AF detection holds several interesting properties, and can be implemented with just a few arithmetical operations which make it a suitable choice for telecare applications.

Keywords: atrial fibrillation, multivariate data analysis, automatic detection, telemedicine

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Authors: Zafar Iqbal, Sana Irshad Khan

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Organic extract from newly isolated plant growth promoting fungus (PGPF) Penicillium sp EU0013 was subjected to bioassays including anti fungal (disc diffusion) cytotoxicity (brine shrimp lethality), herbicidal (Lemna minor) and nematicidal activities. Metabolite profile of the extract was also assessed using HPLC analysis with the aim to identify bioactive natural products in the extract as new drug candidate(s). The extract showed anti fungal potential against tested fungal pathogens. Growth of the Wilt pathogen Fusarium oxyosproum was inhibited up to 63% when compared to negative reference. Activity against brine shrimps was weak and mortality up to 10% was observed at concentration of 200 µg. mL-1. The extract exhibited no toxicity against Lemna minor frond at 200 µg. mL-1. Nematicidal activity was observed very potent against root knot nematode and LC50 value was calculated as 52.5 ug. mL-1 using probit analysis. Methodically assessment of metabolites profile by HPLC showed the presence of kojic acid (Rt 1.4 min) and aflatoxin B1 (Rt 5.9 min) in the mycellial extract as compared with standards. The major unidentified metabolite was eluted at Rt 8.6 along with other minor peaks. The observed high toxicity against root knot nematode was attributed to the unidentified compounds that make fungal extract worthy of further exploration for isolation and structural characterization studies for development of future commercial nematicidal compound(s).

Keywords: penicillium, nematicidal activity, metabolites, HPLC

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Authors: Gabrielle Peck, Ryan Hayes

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The use of a phi meter allows for definition of equivalence ratio during a fire test. Previous phi meter designs have used expensive catalysts and had restricted portability due to the large furnace and requirement for pure oxygen. The new design of the phi meter did not require the use of a catalyst. The furnace design was based on the existing micro-scale combustion calorimetry (MCC) furnace and operating conditions based on the secondary oxidizer furnace used in the steady state tube furnace (SSTF). Preliminary tests were conducted to study the effects of varying furnace temperatures on combustion efficiency. The SSTF was chosen to validate the phi meter measurements as it can both pre-set and independently quantify the equivalence ratio during a test. The data were in agreement with the data obtained on the SSTF. It was also validated by a comparison of CO2 yields obtained from the SSTF oxidizer and those obtained by the phi meter. The phi meter designed and constructed in this work was proven to work effectively on a bench-scale. The phi meter was then used to measure the equivalence ratio on a series of large-scale ISO 9705 tests for numerous fire conditions. The materials used were a range of non-homogenous materials such as polyurethane. The measurements corresponded accurately to the data collected, showing the novel design can be used from bench to large-scale tests to measure equivalence ratio. This cheaper, more portable, safer and easier to use phi meter design will enable more widespread use and the ability to quantify fire conditions of tests, allowing for better understanding of flammability and smoke toxicity.

Keywords: phi meter, smoke toxicity, fire condition, ISO9705, novel equipment

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Authors: Amna Beshir Medani Ahmed, Samia Mohammed Ali El Badwi, Ahmed El Amin Mohammed

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This work has been managed to yield toxicity information on water treatment agents in the Sudan namely polyDADMAC, using New Zealand rabbits at multiple daily oral doses for a period of 10 weeks. Thirty-three heads of New Zealand rabbits were divided into 11 groups, each of three. Group 1 animals were the undosed controls. Test groups of either species were given polyDADMAC at similar dose rates of 0.5, 2.5, 4.5, 10, 15, 20, 25, 50, 100 and 150 mg/kg body weight respectively for groups 2,3,4,5,6,7,8,9,10 and 11. Clinical signs were closely observed with postmortem and histopathological examinations. Chemical investigations included enzymatic concentrations of ALP, GOT, CK, GPT and LDH together with hematological changes in Hb, PCV, RBCs and WBCs. Mortalities occurred to variable degrees irrespective of the dose level. On polyDADMAC challenge, the test species showed clinical signs of dullness, loss of weight, anorexia, diarrhea, difficulty in respiration, hind limb paralysis and recumbency. Notably oral dosing with polyDADMAC caused lung emphysema, hepatic and renal dysfunctions, irregularity in enzymatic activities and serum metabolites, sloughing of intestinal epithelium, decreased electrolytes in serum, and splenic haemosiderosis. On evaluation of the above results, polyDADMAC was considered toxic to New Zealand rabbits at all dose rates tried. Practical implications of the results were highlighted and suggestions for future work were put forward.

Keywords: polydiallyldiethylaluminiumchloride (polyDADMAC), nubian goats, toxicity of drinking water, treatment of drinking water using chemicals

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Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: N. Haj Salem, M. Belhadj, S. Ben Jomâa, S. Saadi, R. Dhouieb, A. Chadly

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Introduction: Sudden death in young is seen as a dramatic phenomenon requiring knowledge of its impact and determining their causes. Aim: We aim to study the epidemiological characteristics of sudden death in young, and to discuss the mechanism and the importance of autopsy in these situations. Material and methods: We performed a retrospective cohort study using autopsy data from the department of forensic medicine at the University Hospital of Fattouma Bourguiba, Monastir-Tunisia. A review of all autopsies performed during 23 years was done. In each case, clinical information and circumstances of death were obtained. We have included all sudden death in persons aged between 1 year and 35 years for the male and from one year to 45 years for female. We collected 312 cases of sudden death during the studied period. The collected data were processed using SPSS 20. The significance level was set at 0.05. Results: Thirty-two cases of cardiac ischemic sudden death have been collected. Myocardial infarction was the second cause of sudden death in young patients. There was a male predominance. The most affected subjects were aged between 25-45 years. The death occurred more frequently at rest. Coronary artery disease has been discovered in twenty-four cases (75%). A severe coronary artery disease was observed in two children with medical history of familial hypercholesterolemia. The myocardial infarction occurred in healthy coronary arteries in eight cases. An anomalous course of coronary arteries, in particular, myocardial bridging, was found in eight cases (25%). Toxicological screening was negative in all cases. Second cause of death was hypertrophic cardiomyopathy. Neurological and respiratory causes of death were implicated respectively in 10% and 15%. Conclusion: Identifying epidemiological characteristics of sudden death in this population is important for guiding approaches to prevention that must be based on dietary hygienic measures and the control of cardiovascular risk factors.

Keywords: autopsy, cardiac death, sudden death, young

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Authors: Hakima Althalb

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Petroleum contamination of sandy soils is a severe environmental problem in Libya, but relatively little work has been carried out to optimize the bioremediation of such heavily contaminated soil, particularly at a pilot scale. The purpose of this research was to determine the potential for the microbial-based bioremediation of hydrocarbon-contaminated soil obtained from an oil refinery in Libya and to assess the potential of both ozonation and phytoremediation (both applied after initial bioremediation) to reduce residual hydrocarbon levels. Plots containing 500 kg soil (triplicates) (contaminated soil diluted with clean soil 50% volume) were set up, (designated as Land Treatment Units; LTUs) containing five different nutrient levels and mixtures (Urea + NPK (nitrogen; phosphor; potassium) mixtures) to obtain C:N:P ratios 100:10:1, and monitored for 90 days. Hydrocarbon levels, microbial numbers, and toxicity (EC50 using luminescent microbial based tests) were assessed. Hydrocarbon levels in non-diluted and diluted soil ranged from 20 733-22 366 mg/kg and from 16 000-17 000 mg/kg respectively. Although all the land treatment units revealed a significant hydrocarbon reduction over time, the highest reduction in hydrocarbon levels obtained was around 60%. For example, 63% hydrocarbon removal was observed using a mixture of urea and NPK with a C:N:P ratio of 100:10:1). Soil toxicity (as assessed using luminescence based toxicity assays) reduced in line with the reduction in total petroleum hydrocarbons observed. However, as relatively high residual TPH (total petroleum hydrocarbon) levels (ranging from 6033-14166mg/kg) were still present after initial bioremediation two ‘post-treatments’ (phytoremediation and ozonation) were attempted to remove residual hydrocarbons remaining. Five locally grown (agriculturally important) plant species were tested. The germination of all plants examined was strongly inhibited (80-100%) and seedlings failed to grow well in the contaminated soil, indicating that the previously bioremediated soils were still toxic to the plants. Subsequent ozonation followed by another bioremediation of soil was more successful than phytoremediation. But even the most promising successful treatment in this study (ozonation for 6 hours at 25ppm followed by bioremediation) still only removed approximately 31% of the residual hydrocarbons. Overall, this work showed that the bioremediation of such highly contaminated soils is difficult and that a combination of treatments would be required to achieve successful remediation. Even after initial dilution and bioremediation the soils remained toxic to plant growth and were therefore not suitable for phytoremediation.

Keywords: bioremediation, petroleum hydrocarbons, ozone, phytoremediation

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Authors: Chikang Wang, Jhongjheng Jian, Poming Huang

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Among a wide variety of pharmaceutical compounds, tetracycline antibiotics are one of the largest groups of pharmaceutical compounds extensively used in human and veterinary medicine to treat and prevent bacterial infections. Because it is water soluble, biologically active, stable and bio-refractory, release to the environment threatens aquatic life and increases the risk posed by antibiotic-resistant pathogens. In practice, due to its antibacterial nature, tetracycline cannot be effectively destructed by traditional biological methods. Hence, in this study, two advanced oxidation processes such as ozonation and sono-Fenton processes were conducted individually to degrade the tetracycline for investigating their feasibility on tetracycline degradation. Effect of operational variables on tetracycline degradation, release of nitrogen and change of toxicity were also proposed. Initial tetracycline concentration was 50 mg/L. To evaluate the efficiency of tetracycline degradation by ozonation, the ozone gas was produced by an ozone generator (Model LAB2B, Ozonia) and introduced into the reactor with different flows (25 - 500 mL/min) at varying pH levels (pH 3 - pH 11) and reaction temperatures (15 - 55°C). In sono-Fenton system, an ultrasonic transducer (Microson VCX 750, USA) operated at 20 kHz combined with H₂O₂ (2 mM) and Fe²⁺ (0.2 mM) were carried out at different pH levels (pH 3 - pH 11), aeration gas and flows (air and oxygen; 0.2 - 1.0 L/min), tetracycline concentrations (10 - 200 mg/L), reaction temperatures (15 - 55°C) and ultrasonic powers (25 - 200 Watts), respectively. Sole ultrasound was ineffective on tetracycline degradation, where the degradation efficiencies were lower than 10% with 60 min reaction. Contribution of Fe²⁺ and H₂O₂ on the degradation of tetracycline was significant, where the maximum tetracycline degradation efficiency in sono-Fenton process was as high as 91.3% followed by 45.8% mineralization. Effect of initial pH level on tetracycline degradation was insignificant from pH 3 to pH 6 but significantly decreased as the pH was greater than pH 7. Increase of the ultrasonic power was slightly increased the degradation efficiency of tetracycline, which indicated that the hydroxyl radicals dominated the oxidation of tetracycline. Effects of aeration of air or oxygen with different flows and reaction temperatures were insignificant. Ozonation showed better efficiencies in tetracycline degradation, where the optimum reaction condition was found at pH 3, 100 mL O₃/min and 25°C with 94% degradation and 60% mineralization. The toxicity of tetracycline was significantly decreased due to the mineralization of tetracycline. In addition, less than 10% of nitrogen content was released to solution phase as NH₃-N, and the most degraded tetracycline cannot be full mineralized to CO₂. The results shown in this study indicated that both the sono-Fenton process and ozonation can effectively degrade the tetracycline and reduce its toxicity at profitable condition. The costs of two systems needed to be further investigated to understand the feasibility in tetracycline degradation.

Keywords: degradation, detoxification, mineralization, ozonation, sono-Fenton process, tetracycline

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Authors: Siti Rajaah Binti Sayed Sultan

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Managing the code blue event is stressful for nurses, the patient, and the patient's families. The rapid response from the first and second responders in the code blue event will improve patient outcomes and prevent tissue hypoxia that leads to brain injury and other organ failures. Providing 1 minute for the cardiac massage and 2 minutes for defibrillation will significantly improve patient outcomes. As we know, the American Heart Association came out with guidelines for managing cardiac arrest patients. The hospital must provide competent staff to manage this situation. It can be achieved when the staff is well equipped with the skill, attitude, and knowledge to manage this situation with well-planned strategies, i.e., clear guidelines for managing the code blue event, competent staff, and functional equipment. The code blue simulation (CBS) was chosen in the training program for code blue management because it can mimic real scenarios. Having the code blue simulation module will allow the staff to appreciate what they will face during the code blue event, especially since it rarely happens in that area. This CBS module training will help the staff familiarize themselves with the activities that happened during actual events and be able to operate the equipment accordingly. Being challenged and independent in managing the code blue in the early phase gives the patient a better outcome. The CBS module will help the assessor and the hospital management team with the proper tools and guidelines for managing the code blue drill accordingly. As we know, prompt action will benefit the patient and their family. It also indirectly increases the confidence and job satisfaction among the nurses, increasing the standard of care, reducing the complication and hospital burden, and enhancing cost-effective care.

Keywords: code blue simulation module, development of code blue simulation module, code blue response time, code blue drill, cardiorespiratory arrest, managing code blue

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Authors: K. Rasool

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Sulfate-reducing bacteria (SRBs) induced biofilm formation is a global industrial concern due to its role in the development of microbial-induced corrosion (MIC). Herein, we have developed a biodegradable chitosan/lignosulfonate nanocomposite (CS@LS) as an efficient green biocide for the inhibition of SRBs biofilms. We investigated in detail the inhibition mechanism of SRBs by CS@LS in seawater media. Stable CS@LS-1:1 with 150–200 nm average size and zeta potential of + 34.25 mV was synthesized. The biocidal performance of CS@LS was evaluated by sulfate reduction profiles coupled with analysis of extracted extracellular polymeric substances (EPS) and lactate dehydrogenase (LDH) release assays. As the nanocomposite concentration was increased from 50 to 500 µg/mL, the specific sulfate reduction rate (SSRR) decreased from 0.278 to 0.036 g-sulfate/g-VSS*day showing a relative sulfate reduction inhibition of 86.64% as compared to that of control. Similarly, the specific organic uptake rate (SOUR) decreased from 0.082 to 0.039 0.036 g-TOC/g-VSS*day giving a relative co-substrate oxidation inhibition of 52.19% as compared to that of control. The SRBs spiked with 500 µg/mL CS@LS showed a reduction in cell viability to 1.5 × 106 MPN/mL. To assess the biosafety of the nanocomposite on the marine biota, the 72-hours acute toxicity assays using the zebrafish embryo model revealed that the LC50 for the CS@LS was 103.3 µg/mL. Thus, CS@LS can be classified as environmentally friendly. The nanocomposite showed long-term stability and excellent antibacterial properties against SRBs growth and is thus potentially useful for combating the problems of biofilm growth in harsh marine and aquatic environments.

Keywords: green biocides, chitosan/lignosulfonate nanocomposite, SRBs, toxicity

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

Procedia PDF Downloads 125

Authors: Wei-Chih Huang, Pei-Lung Chung, Ching-Heng Lin, Hsuan-Chia Yang, Der-Ming Liou

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Background: In-Hospital Cardiac Arrest (IHCA) threaten life of the inpatients, cause serious effect to patient safety, quality of inpatients care and hospital service. Health providers must identify the signs of IHCA early to avoid the occurrence of IHCA. This study will consider the potential association between early signs of IHCA and the essence of patient care provided by nurses and other professionals before an IHCA occurs. The aim of this study is to identify significant associations between nursing interventions and abnormal early evaluation results of IHCA that can assist health care providers in monitoring inpatients at risk of IHCA to increase opportunities of IHCA early detection and prevention. Materials and Methods: This study used one of the data mining techniques called association rules mining to compute associations between nursing interventions and abnormal early evaluation results of IHCA. The nursing interventions and abnormal early evaluation results of IHCA were considered to be co-occurring if nursing interventions were provided within 24 hours of last being observed in abnormal early evaluation results of IHCA. The rule based methods were utilized 23.6 million electronic medical records (EMR) from a medical center in Taipei, Taiwan. This dataset includes 733 concepts of nursing interventions that coded by clinical care classification (CCC) codes and 13 early evaluation results of IHCA with binary codes. The values of interestingness and lift were computed as Q values to measure the co-occurrence and associations’ strength between all in-hospital patient care measures and abnormal early evaluation results of IHCA. The associations were evaluated by comparing the results of Q values and verified by medical experts. Results and Conclusions: The results show that there are 4195 pairs of associations between nursing interventions and abnormal early evaluation results of IHCA with their Q values. The indication of positive association is 203 pairs with Q values greater than 5. Inpatients with high blood sugar level (hyperglycemia) have positive association with having heart rate lower than 50 beats per minute or higher than 120 beats per minute, Q value is 6.636. Inpatients with temporary pacemaker (TPM) have significant association with high risk of IHCA, Q value is 47.403. There is significant positive correlation between inpatients with hypovolemia and happened abnormal heart rhythms (arrhythmias), Q value is 127.49. The results of this study can help to prevent IHCA from occurring by making health care providers early recognition of inpatients at risk of IHCA, assist with monitoring patients for providing quality of care to patients, improve IHCA surveillance and quality of in-hospital care.

Keywords: in-hospital cardiac arrest, patient safety, nursing intervention, association rule mining

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Authors: Nesrine Benarous, Hassiba Bougueria, Nabila Moussa Slimane, Aouatef Cherouana

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Crystal polymorphism is important for the synthesis of more potent and bioactive pharmaceutical compounds, including their different properties, such as packing arrangement and conformation. In fact, polymorphism plays a vital role in drug development. Different parameters affect the crystallization and give their degree of freedom. Severalproperties affected polymorphism, like kinetics, thermodynamics, spectroscopy, and mechanical property. Various techniques are used for characterizing polymorphs, are crystallography, morphology, phase transitions, molecular motion, and chemical environment. In this work, crystal structures of two polymorphs (I and II) of the Schiff base (SB) title compound were prepared by condensation reaction. The crystal structures of both polymorphs were determined by single X-ray analysis. The two polymorphs crystallize in two different space groups: P21/c for I and Pbca for II. The dihedral angles between the two phenyl rings are 4.81º for I and 82.27º for II. Both crystal structures are built on the basis of moderate and weak hydrogen bonds, 𝜋-stacking, and halogen⋯halogeninteractions. On the other hand, Hirshfeld surface (HS) analysis indicates that the most important contributions to the crystal packing for the two polymorphs are from Cl⋯H/H⋯Cl, H⋯H, and N⋯H/H⋯N contacts. These are followed by C⋯H/H⋯C for compound I and C⋯C and by C⋯H/H⋯C contacts for compound II. Afterwards, the in vitro antibacterial activity revealed that the SB have been found effective against G- bacteria Klebsiella pneumonia andG+ bacteria Staphylococcus aureuswith MIC value of14.37μg/mL. Moreover, the SBexhibited moderate toxicity against Brine Shrimp with LC50 value of 44.19μg/mL.

Keywords: polymorph, crystal structure, hirshfeld surface analysis, in vitro antibacterial activity, toxicity

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Authors: Stephanie PB Caligiuri, Harold M Aukema, Delfin Rodriguez-Leyva, Amir Ravandi, Randy Guzman, Grant N. Pierce

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Background: Hypertension leads to cardiac and cerebral events and therefore is the leading risk factor attributed to death in the world. Oxylipins may be mediators in these events as they can regulate vascular tone and inflammation. Oxylipins are derived from fatty acids. Dietary flaxseed is rich in the n3 fatty acid, alpha-linolenic acid, and, therefore, may have the ability to change the substrate profile of oxylipins. As a result, this could alter blood pressure. Methods: A randomized, double-blinded, controlled clinical trial, the Flax-PAD trial, was used to assess the impact of dietary flaxseed on blood pressure (BP), and to also assess the relationship of plasma oxylipins to BP in 81 patients with peripheral arterial disease (PAD). Patients with PAD were chosen for the clinical trial as they are at an increased risk for hypertension and cardiac and cerebral events. Thirty grams of ground flaxseed were added to food products to consume on a daily basis for 6 months. The control food products contained wheat germ, wheat bran, and mixed dietary oils instead of flaxseed. Central BP, which is more significantly associated to organ damage, cardiac, and cerebral events versus brachial BP, was measured by pulse wave analysis at baseline and 6 months. A plasma profile of 43 oxylipins was generated using solid phase extraction, HPLC-MS/MS, and stable isotope dilution quantitation. Results: At baseline, the central BP (systolic/diastolic) in the placebo and flaxseed group were, 131/73 ± 2.5/1.4 mmHg and 128/71 ± 2.6/1.4 mmHg, respectively. After 6 months of intervention, the flaxseed group exhibited a decrease in blood pressure of 4.0/1.0 mmHg. The 6 month central BP in the placebo and flaxseed groups were, 132/74 ± 2.9/1.8 mmHg and 124/70 ± 2.6/1.6 mmHg (P<0.05). Correlation and logistic regression analyses between central blood pressure and oxylipins were performed. Significant associations were observed between central blood pressure and 17 oxylipins, primarily produced from arachidonic acid. Every 1 nM increase in 16-hydroxyeicosatetraenoic acid (HETE) increased the odds of having high central systolic BP by 15-fold, of having high central diastolic BP by 6-fold and of having high central mean arterial pressure by 15-fold. In addition, every 1 nM increase in 5,6-dihydroxyeicosatrienoic acid (DHET) and 11,12-DHET increased the odds of having high central mean arterial pressure by 45- and 18-fold, respectively. Flaxseed induced a significant decrease in these as well as 4 other vasoconstrictive oxylipins. Conclusion: Dietary flaxseed significantly lowered blood pressure in patients with PAD and hypertension. Plasma oxylipins were strongly associated with central blood pressure and may have mediated the flaxseed-induced decrease in blood pressure.

Keywords: hypertension, flaxseed, oxylipins, peripheral arterial disease

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Authors: Walaa G. Hozayen, Osama M. Ahmed, Haidy T. Abo Sree

Abstract:

The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects.

Keywords: doxorubicin, purslane, testis function, antioxidants

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

Abstract:

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 247

Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet

Abstract:

Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.

Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation

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Authors: Pei-Ying Lo, Jing-Hao Ciou, Kai-Cheng Yang, Jia-Huei Zheng, Shih-Hsiang Huang, Kuen-Chan Lee, Er-Chieh Cho

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As-produced CNTs are insoluble in all organic solvents and aqueous solutions have imposed limitations to the use of CNTs. Therefore, how to debundle carbon nanotubes and to modify them for further uses is an important issue. There are several methods for the dispersion of CNTs in water using covalent attachment of hydrophilic groups to the surface of tubes. These methods, however, alter the electronic structure of the nanotubes by disrupting the network of sp2 hybridized carbons. In order to keep the nanotubes’ intrinsic mechanical and electrical properties intact, non-covalent interactions are increasingly being explored as an alternative route for dispersion. Apart from conventional surfactants such as sodium dodecylsulfate (SDS) or sodium dodecylbenzenesulfonate (SDBS) which are highly effective in dispersing CNTs, biopolymers have received much attention as dispersing agents due to the anticipated biocompatibility of the dispersed CNTs. Also, The pyrenyl group is known to interact strongly with the basal plane of graphene via π-stacking. In this study, a highly re-dispersible biopolymer is reported for the synthesis of pyrene-modified poly-L-lysine (PBPL) and poly(D-Glu, D-Lys) (PGLP). To provide the evidence of the safety of the PBPL/CNT & PGLP/CNT materials we use in this study, H1299 and HCT116 cells were incubated with PBPL/CNT & PGLP/CNT materials for toxicity analysis, MTS assays. The results from MTS assays indicated that no significant cellular toxicity was shown in H1299 and HCT116 cells. Furthermore, the fluorescence marker fluorescein isothiocyanate (FITC) was added to PBPL & PGLP dispersions. From the fluorescent measurements showed that the chemical functionalisation of the PBPL/CNT & PGLP/CNT conjugates with the fluorescence marker were successful. The fluorescent PBPL/CNT & PGLP/CNT conjugates could find application in medical imaging. In the next step, the GFP gene is immobilized onto PBPL/CNT conjugates by introducing electrostatic interaction. GFP-transfected cells that emitted fluorescence were imaged and counted under a fluorescence microscope. Due to the unique biocompatibility of PBPL modified CNTs, the GFP gene could be transported into H1299 cells without using antibodies. The applicability of such soluble and chemically functionalised polypeptide/CNT conjugates in biomedicine is currently investigated. We expect that this polypeptide/CNT system will be a safe and multi-functional nanomedical delivery platform and contribute to future medical therapy.

Keywords: carbon nanotube, nanotoxicology, GFP transfection, polypeptide/CNT hybrids

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