Search results for: metabolism and excretion–toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1462

Search results for: metabolism and excretion–toxicity

1012 Phytoremediation of Pharmaceutical Emerging Contaminant-Laden Wastewater: A Techno-Economic and Sustainable Development Approach

Authors: Reda A. Elkhyat, Mahmoud Nasr, Amel A. Tammam, Mohamed A. Ghazy

Abstract:

Pharmaceuticals and personal care products (PPCPs) are a unique group of emerging contaminants continuously introduced into the aquatic ecosystem at concentrations capable of inducing adverse effects on humans and aquatic organisms, even at trace levels ranging from ppt to ppm. Amongst the common pharmaceutical emerging pollutants detected in several aquatic environments, acetaminophen has been recognized for its high toxicity. Once released into the aquatic environment, acetaminophen could be degraded by the microbial community and adsorption/ uptake by the plants. Although many studies have investigated the hazard risks of acetaminophen pollutants on aquatic animals, the number of studies demonstrating its removal efficiency and effects on the aquatic plant still needs to be expanded. In this context, this study aims to apply the aquatic plant-based phytoremediation system to eliminate this emerging contaminant from domestic wastewater. The phytoremediation experiment was performed in a hydroponic system containing Eichhornia crassipes and operated under the natural environment at 25°C to 30°C. This system was subjected to synthetic domestic wastewater with the maximum initial chemical oxygen demand (COD) of 390 mg/L and three different acetaminophen concentrations of 25, 50, and 200 mg/L. After 17 d of operation, the phytoremediation system achieved removal efficiencies of about 100% and 85.6±4.2% for acetaminophen and COD, respectively.Moreover, the Eichhornia crassipes could withstand the toxicity associated with increasing the acetaminophen concentrations from 25 to 200 mg/L. This high treatment performance could be assigned to the well-adaptation of the water hyacinth to the phytoremediation factors. Moreover, it has been proposed that this phytoremediation system could be largely supported by phytodegradation and plant uptaking mechanisms; however, detecting the generated intermediates, metabolites, and degradation products are still under investigation. Applying this free-floating plant in wastewater treatment and reducing emerging contaminants would meet the targets of SDGs 3, 6, and. 14. The cost-benefit analysis was performed for the phytoremediation system. The phytoremediation system is financially viable as the net profit was 2921 US $/ y with a payback period of nine years.

Keywords: domestic wastewater, emerging pollutants, hydrophyte Eichhornia crassipes, paracetamol removal efficiency, sustainable development goals (SDGs)

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1011 Acute Effects of Exogenous Hormone Treatments on Postprandial Acylation Stimulating Protein Levels in Ovariectomized Rats After a Fat Load

Authors: Bashair Al Riyami

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Background: Acylation stimulating protein (ASP) is a small basic protein that was isolated based on its function as a potent lipogenic factor. The role of ASP in lipid metabolism has been described in numerous studies. Several association studies suggest that ASP may play a prominent role in female fat metabolism and distribution. Progesterone is established as a female lipogenic hormone, however the mechanisms by which progesterone exert its effects are not fully understood. AIM: Since ASP is an established potent lipogenic factor with a known mechanism of action, in this study we aim to investigate acute effects of different hormone treatments on ASP levels in vivo after a fat load. Methods: This is a longitudinal study including 24 female wister rats that were randomly divided into 4 groups including controls (n=6). The rats were ovariectomized, and fourteen days later the fasting rats were injected subcutaneously with a single dose of different hormone treatments (progesterone, estrogen and testosterone). An hour later, olive was administered by oral gavage, and plasma blood samples were collected at several time points after oil administration for ASP and triglyceride measurements. Area under the curve (TG-AUC) was calculated to represent TG clearance Results: RM-ANCOVA and post-analysis showed that only the progesterone treated group had a significant postprandial ASP increase at two hours compared to basal levels and to the controls (439.8± 62.4 vs 253.45± 59.03 ug/ml), P= 0.04. Interestingly, increased postprandial ASP levels coordinated negatively with corresponding TG levels and TG-AUC across the postprandial period most apparent in the progesterone and testosterone treated groups that behaved in an opposite manner. ASP levels were 3-fold higher in the progesterone compared to the testosterone treated group, whereas TG-AUC was significantly lower in the progesterone treated group compared to the testosterone treated group. Conclusion: These findings suggest that progesterone treatment enhances ASP production and TG clearance in a simultaneous manner. The strong association of postprandial ASP levels and TG clearance in the progesterone treated group support the notion of a stimulatory role for progesterone on ASP mediated TG clearance. This is the first functional study to demonstrate a cause-effect relationship between hormone treatment and ASP levels in vivo. These findings are promising and may contribute to further understanding the mechanism of progesterone function as a female lipogenic hormone through enhancing ASP production and plasma levels.

Keywords: ASP, lipids, sex hormones, wister rats

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1010 Differential Proteomics Expression in Purple Rice Supplemented Type 2 Diabetic Rats’ Skeletal Muscle

Authors: Ei Ei Hlaing, Narissara Lailerd, Sittiruk Roytrakul, Pichapat Piamrojanaphat

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Type 2 diabetes is one of the most common metabolic diseases all over the world. The pathogenesis of type 2 diabetes is not the only dysfunction of pancreatic beta cells but also insulin resistance in muscle, liver and adipose tissue. High levels of circulating free fatty acids, an increased lipid content of muscle cells, impaired insulin-mediated glucose uptake and diminished mitochondrial functioning are pathophysiological hallmarks of diabetic skeletal muscles. Purple rice (Oryza sativa L. indica) has been shown to have antidiabetic effects. However, the underlying mechanism(s) of antidiabetic activity of purple rice is still unraveled. In this research, to explore in-depth cellular mechanism(s), proteomic profile of purple rice supplemented type 2 diabetic rats’ skeletal muscle were analyzed contract with non-supplemented rats. Diabetic rats were induced high-fat diet combined with streptozotocin injection. By using one- dimensional gel electrophoresis (1-DE) and LC-MS/MS quantitative proteomic method, we analyzed proteomic profiles in skeletal muscle of normal rats, normal rats with purple rice supplementation, type 2 diabetic rats, and type 2 diabetic rats with purple rice supplementation. Total 2676 polypeptide expressions were identified. Among them, 24 peptides were only expressed in type 2 diabetic rats, and 24 peptides were unique peptides in type 2 diabetic rats with purple rice supplementation. Acetyl CoA carboxylase 1 (ACACA) found as unique protein in type 2 diabetic rats which is the major enzyme in lipid synthesis and metabolism. Interestingly, DNA damage response protein, heterogeneous nuclear ribonucleoprotein K [Mus musculus] (Hnrnpk), was upregulated in type 2 diabetic rats’ skeletal muscle. Meanwhile, unique proteins of type 2 diabetic rats with purple rice supplementation (bone morphogenetic 7 protein preproprotein, BMP7; and forkhead box protein NX4, Foxn4) involved with muscle cells growth through the regulation of TGF-β/Smad signaling network. Moreover, BMP7 may effect on insulin signaling through the downstream signaling of protein kinase B (Akt) which acts in protein synthesis, glucose uptake, and glycogen synthesis. In conclusion, our study supports that type 2 diabetes impairs muscular lipid metabolism. In addition, purple rice might recover the muscle cells growth and insulin signaling.

Keywords: proteomics, purple rice bran, skeletal muscle, type 2 diabetic rats

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1009 Exploring the Safety of Sodium Glucose Co-Transporter-2 Inhibitors at the Imperial College London Diabetes Centre, UAE

Authors: Raad Nari, Maura Moriaty, Maha T. Barakat

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Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs with a unique mechanism of action. They are used to improve glycaemic control in adults with type 2 diabetes by enhancing urinary glucose excretion. In the UAE, there has been certainly an increased use of these medications. As with any new medication, there are safety considerations related to their use in patients with type two diabetes. A retrospective study was conducted at the three main centres of the Imperial College London Diabetes Centre. Methodology: All patients in electronic database (Diamond) from October 2014 to October 2017 were included with a minimum of six months usage of sodium glucose co-transporter inhibitors that comprise canagliflozin, dapagliflozin and empagliflozin. There were 15 paired sample biochemical and clinical correlations. The analysis was done at the start of the study, three months and six months apart. SPSS version 24 was used for this study. Conclusion: This study of sodium glucose co-transporter-2 inhibitors used showed significant reductions in weight, glycated haemoglobin A1C, systolic and diastolic blood pressures. As the case with systematic reviews, there were similar changes in liver enzymes, raised total cholesterol, low density lipopoptein and high density lipoprotein. There was slight improvement in estimated glomerular filtration rate too. Our analysis also showed that they increased in the incidence of urinary tract symptoms and incidence of urinary tract infections.

Keywords: SGLT2 inhibitors dapagliflozin empagliflozin canagliflozin, adverse effects, amputation diabetic ketoacidosis DKA, urinary tract infection

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1008 Antimicrobial Effects and Phytochemical Analysis of Chrysophyllum Albidum Plant Parts (Leaves, Roots and Seeds) Extracts on Bacterial Isolates from Urinary Catheters

Authors: Ebere Christian Ugochukwu, Okafor Josephine, Oyawoye Tomisin

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The occurrence of multidrug resistance patterns that have been developed by bacteria has made it difficult to properly treat infections using standard clinical medications. Hence, the use of herbs as an alternative source of therapy is considered cheap and easily accessible to locals. This research explored the antimicrobial effects of aqueous and ethanolic extracts obtained from Chrysophyllum albidum (commonly called ‘Agbalumo’ in southwest Nigeria and ‘Udara’ in the eastern and southern parts of Nigeria) plant parts (leaves, roots and seeds) against bacteria isolated from urinary catheter tips. The following isolates were obtained; Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Klebsiella aerogenes. The agar well diffusion method was used. The average percentages of antimicrobial resistance of the isolates to gentamycin were 45.5% for P. aeruginosa, 42.1% for E. coli, 46.9% for K. aerogenes, and ˃90% for other isolates. Qualitative phytochemical screening of the plant parts extracts was done using chemical test for the screening and identification of bioactive chemical constituents. The ethanolic extract mixtures (leaf, root and seed) had the greatest effect on all the isolates, with inhibition zones (IZs) ranging from 8-26 mm and MICs ranging from <16-32 mg/ml. The Potencies of the C. albidum extracts based on the IZ and MIC values were greater in the extract mixtures, followed by those in the roots. Phytochemical screening revealed that all the extracts contained phenol except for the seeds while tannins were present in all the extracts except the leaves. The activity of the ethanolic extracts of each part at high and low concentrations was greater than that of the aqueous extracts at the same concentrations (p<0.05). The acute toxicity results showed that the LD50 of the extracts was ˃5000 mg/body weight, indicating no toxicity. The antibacterial activities of the extract mixtures and roots on the isolates confirmed the use of C. albidum in folk medicine for the treatment of CAUTIs, hence indicating its antibacterial potential for use in novel antibiotic production.

Keywords: antimicrobials, susceptibility, minimum inhibitory concentration, extracts

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1007 Comprehensive Longitudinal Multi-omic Profiling in Weight Gain and Insulin Resistance

Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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1006 Associations among Fetuin A, Cortisol and Thyroid Hormones in Children with Morbid Obesity and Metabolic Syndrome

Authors: Mustafa Metin Donma, Orkide Donma

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Obesity is a disease with an ever-increasing prevalence throughout the world. The metabolic network associated with obesity is very complicated. In metabolic syndrome (MetS), it becomes even more difficult to understand. Within this context, hormones, cytokines, and many others participate in this complex matrix. The collaboration among all of these parameters is a matter of great wonder. Cortisol, as a stress hormone, is closely associated with obesity. Thyroid hormones are involved in the regulation of energy as well as glucose metabolism with all of its associates. Fetuin A is known for years; however, the involvement of this parameter in obesity discussions is rather new. Recently, it has been defined as one of the new generation markers of obesity. In this study, the aim was to introduce complex interactions among all to be able to make clear comparisons, at least for a part of this complicated matter. Morbid obese (MO) children participated in the study. Two groups with 46 MO children and 43 with MetS were constituted. All children included in the study were above 99th age- and sex-adjusted body mass index (BMI) percentiles according to World Health Organization criteria. Forty-three morbid obese children in the second group had also MetS components. Informed consent forms were filled by the parents of the participants. The institutional ethics committee has given approval for the study protocol. Data as well as the findings of the study were evaluated from a statistical point of view. Two groups were matched for their age and gender compositions. Significantly higher body mass index (BMI), waist circumference, thyrotropin, and insulin values were observed in the MetS group. Triiodothyronine concentrations did not differ between the groups. Elevated levels for thyroxin, cortisol, and fetuin-A were detected in the MetS group compared to the first group (p > 0.05). In MO MetS- group, cortisol was correlated with thyroxin and fetuin-A (p < 0.05). In the MO MetS+ group, none of these correlations were present. Instead, a correlation between cortisol and thyrotropin was found (p < 0.05). In conclusion, findings have shown that cortisol was the key player in severely obese children. The association of this hormone with the participants of thyroid hormone metabolism was quite important. The lack of association with fetuin A in the morbid obese MetS+ group has suggested the possible interference of MetS components in the behavior of this new generation obesity marker. The most remarkable finding of the study was the unique correlation between cortisol and thyrotropin in the morbid obese MetS+ group, suggesting that thyrotropin may serve as a target along with cortisol in the morbid obese MetS+ group. This association may deserve specific attention during the development of remedies against MetS in the pediatric population.

Keywords: children, cortisol, fetuin A, morbid obesity, thyrotropin

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1005 Carbendazim Toxicity and Ameliorative Effect of Vitamin E in African Giant Rats

Authors: A. O. Omonona, T. A. Jarikre

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Increase specialization in agriculture and use of pesticides may inadvertently cause ecosystem degradation and eventually loss of biodiversity. The populations of numerous wildlife species have undergone a precipitous decline. Many of these problems have been attributed directly to habitat loss and over exploitation resulting from unregulated pesticide uses. Carbendazim a broad spectrum benzimidazole fungicide and a metabolite of benomyl, is used to control plant disease in cereals and fruit. The effect of carbendazim exposure and the ameliorative effect of tocopherol (vitamin E) were assessed on African giant rat AGR. Hematological, biochemical and histological changes were used to determine the health condition of the animals exposed to pesticide. Sixteen AGR were stabilized, weighed and then divided into four experimental groups (A to D). Two groups were pretreated with vitamin. Group A was exposed to carbendazim only, B- carbendazim + vitamin, C- vitamin only, and D- blank (control). Packed cell volume PCV was estimated by the microhematocrit method, Leucocyte and Platelet counts were determined using the hemocytometric method. Cholinesterase (AchE) and markers of oxidative stress were quantified, and tissue changes examined microscopically. There were no behavioral changes observed in the animals, but there was a decrease in body weight and abortion after 23 days of exposure to carbendazim. There was significant differences in the packed cell volume, the hemoglobin concentration and the red blood cell counts (p < 0.05). The increases in malonyl aldehyde MDA was significant (p < 0.05) in the pesticide intoxicated rats compared to control. Vitamin E supplementation reduced MDA level significantly (p < 0.05). There was a sharp remarkable decrease in acetylcholinesterase levels in the pesticide intoxicated rats (p < 0.05). Vitamin E supplementation normalise the AchE levels comparable to that in control. Grossly, the vital organs appeared normal in the pesticide exposed and control groups except moderate pulmonary congestion. Microscopically, there was severe diffuse hepatocellular swelling in carbendazim exposed group. The severity of hepatocellular injury was reduced in the rats with vitamin E. This study ascertained the toxic effect of carbendazim and antioxidative properties of vitamins in the Africa giant rat.

Keywords: African giant rat, antioxidant, carbendazim, pesticides, toxicity

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1004 Potential Impacts of Maternal Nutrition and Selection for Residual Feed Intake on Metabolism and Fertility Parameters in Angus Bulls

Authors: Aidin Foroutan, David S. Wishart, Leluo L. Guan, Carolyn Fitzsimmons

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Maximizing efficiency and growth potential of beef cattle requires not only genetic selection (i.e. residual feed intake (RFI)) but also adequate nutrition throughout all stages of growth and development. Nutrient restriction during gestation has been shown to negatively affect post-natal growth and development as well as fertility of the offspring. This, when combined with RFI may affect progeny traits. This study aims to investigate the impact of selection for divergent genetic potential for RFI and maternal nutrition during early- to mid-gestation, on bull calf traits such as fertility and muscle development using multiple ‘omics’ approaches. Comparisons were made between High-diet vs. Low-diet and between High-RFI vs. Low-RFI animals. An epigenetics experiment on semen samples identified 891 biomarkers associated with growth and development. A gene expression study on Longissimus thoracis muscle, semimembranosus muscle, liver, and testis identified 4 genes associated with muscle development and immunity of which Myocyte enhancer factor 2A [MEF2A; induces myogenesis and control muscle differentiation] was the only differentially expressed gene identified in all four tissues. An initial metabolomics experiment on serum samples using nuclear magnetic resonance (NMR) identified 4 metabolite biomarkers related to energy and protein metabolism. Once all the biomarkers are identified, bioinformatics approaches will be used to create a database covering all the ‘omics’ data collected from this project. This database will be broadened by adding other information obtained from relevant literature reviews. Association analyses with these data sets will be performed to reveal key biological pathways affected by RFI and maternal nutrition. Through these association studies between the genome and metabolome, it is expected that candidate biomarker genes and metabolites for feed efficiency, fertility, and/or muscle development are identified. If these gene/metabolite biomarkers are validated in a larger animal population, they could potentially be used in breeding programs to select superior animals. It is also expected that this work will lead to the development of an online tool that could be used to predict future traits of interest in an animal given its measurable ‘omics’ traits.

Keywords: biomarker, maternal nutrition, omics, residual feed intake

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1003 Occupational Exposure to Polycyclic Aromatic Hydrocarbons (Pha) among Asphalt and Road Paving Workers

Authors: Boularas El Alia, H. Rezk-Allah, S. Chaoui, A. Chama, B. Rezk-Allah

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Aims: To assess the current exposure to the PHA among various workers in the sector of asphalt and road paving. Methods: The assessment of the exposure to PHA has been performed on workers (n=14) belonging to two companies, allocated into several activities such as road paving, manufacturing of coated bituminous warm, manufacturing of asphalt cut-back, manufacturing of emulsion of asphalt. A group of control subjects (n=18) was associated. The internal exposure to PHA was investigated by measurement of the urinary excretion of 2-naphtol, urine metabolite of naphtalene, one of the biomarkers of total PHA exposure. Urine samples were collected from the exposed workers, at the beginning of the week, at the beginning of the work shift (BWBS) and at the end of the work shift, at the end of the week (ESEW). In the control subjects, single samples of urine were collected after the end of the work shift.Every subject was invited to answer a questionnaire for the collection of technical and medical data as well as smoking habits and food intake. The concentration of 2-naphtol in the hydrolysate of urine was determined spectrophotometrically, after its reaction with the Fast Blue BB salt (diazotized 4-benzoylamino-2,5-diethoxyaniline). Results: For all the workers included in the study, the 2-urinary naphtol concentrations were higher than those in the control subjects (Median=9,55 µg/g creatinine) whether it is at (BWBS) (Md=16,2 µg/g creatinine) or at (ESEW) (n=18,Median=32,22 µg/g creatinine). Considerable differences are observed according to the category of job. The concentrations are also higher among smokers. Conclusion:The results show a significant exposure, mainly during manual laying, reveals an important risk particularly for the respiratory system.Considering the current criteria, carcinogenic risk due to the PHA seems not insignificant.

Keywords: PHA, asphalt, assessment, occupational, exposure

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1002 Investigation of Mutagenicity and DNA Binding Properties of Metal-Free and Metallophthalocyanines Containing α-Napththolbenzein Groups on the Peripheral Positions

Authors: Meltem Betül Sağlam, Halil İbrahim Güler, Aykut Sağlam

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In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.

Keywords: dye, mutagenicity, phthalocyanine, toxicity

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1001 Sustainable Treatment of Vegetable Oil Industry Wastewaters by Xanthomonas campestris

Authors: Bojana Ž. Bajić, Siniša N. Dodić, Vladimir S. Puškaš, Jelena M. Dodić

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Increasing industrialization as a response to the demands of the consumer society greatly exploits resources and generates large amounts of waste effluents in addition to the desired product. This means it is a priority to implement technologies with the maximum utilization of raw materials and energy, minimum generation of waste effluents and/or their recycling (secondary use). Considering the process conditions and the nature of the raw materials used by the vegetable oil industry, its wastewaters can be used as substrates for the biotechnological production which requires large amounts of water. This way the waste effluents of one branch of industry become raw materials for another branch which produces a new product while reducing wastewater pollution and thereby reducing negative environmental impacts. Vegetable oil production generates wastewaters during the process of rinsing oils and fats which contain mainly fatty acid pollutants. The vegetable oil industry generates large amounts of waste effluents, especially in the processes of degumming, deacidification, deodorization and neutralization. Wastewaters from the vegetable oil industry are generated during the whole year in significant amounts, based on the capacity of the vegetable oil production. There are no known alternative applications for these wastewaters as raw materials for the production of marketable products. Since the literature has no data on the potential negative impact of fatty acids on the metabolism of the bacterium Xanthomonas campestris, these wastewaters were considered as potential raw materials for the biotechnological production of xanthan. In this research, vegetable oil industry wastewaters were used as the basis for the cultivation media for xanthan production with Xanthomonas campestris ATCC 13951. Examining the process of biosynthesis of xanthan on vegetable oil industry wastewaters as the basis for the cultivation media was performed to obtain insight into the possibility of its use in the aforementioned biotechnological process. Additionally, it was important to experimentally determine the absence of substances that have an inhibitory effect on the metabolism of the production microorganism. Xanthan content, rheological parameters of the cultivation media, carbon conversion into xanthan and conversions of the most significant nutrients for biosynthesis (carbon, nitrogen and phosphorus sources) were determined as indicators of the success of biosynthesis. The obtained results show that biotechnological production of the biopolymer xanthan by bacterium Xanthomonas campestris on vegetable oil industry wastewaters based cultivation media simultaneously provides preservation of the environment and economic benefits which is a sustainable solution to the problem of wastewater treatment.

Keywords: biotechnology, sustainable bioprocess, vegetable oil industry wastewaters, Xanthomonas campestris

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1000 Breath Ethanol Imaging System Using Real Time Biochemical Luminescence for Evaluation of Alcohol Metabolic Capacity

Authors: Xin Wang, Munkbayar Munkhjargal, Kumiko Miyajima, Takahiro Arakawa, Kohji Mitsubayashi

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The measurement of gaseous ethanol plays an important role of evaluation of alcohol metabolic capacity in clinical and forensic analysis. A 2-dimensional visualization system for gaseous ethanol was constructed and tested in visualization of breath and transdermal alcohol. We demonstrated breath ethanol measurement using developed high-sensitive visualization system. The concentration of breath ethanol calculated with the imaging signal was significantly different between the volunteer subjects of ALDH2 (+) and (-).

Keywords: breath ethanol, ethnaol imaging, biochemical luminescence, alcohol metabolism

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999 Wastewater Treatment Using Ternary Hybrid Advanced Oxidation Processes Through Heterogeneous Fenton

Authors: komal verma, V. S. Moholkar

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In this current study, the challenge of effectively treating and mineralizing industrial wastewater prior to its discharge into natural water bodies, such as rivers and lakes, is being addressed. Particularly, the focus is on the wastewater produced by chemical process industries, including refineries, petrochemicals, fertilizer, pharmaceuticals, pesticides, and dyestuff industries. These wastewaters often contain stubborn organic pollutants that conventional techniques, such as microbial processes cannot efficiently degrade. To tackle this issue, a ternary hybrid technique comprising of adsorption, heterogeneous Fenton process, and sonication has been employed. The study aims to evaluate the effectiveness of this approach for treating and mineralizing wastewater from a fertilizer industry located in Northeast India. The study comprises several key components, starting with the synthesis of the Fe3O4@AC nanocomposite using the co-precipitation method. The nanocomposite is then subjected to comprehensive characterization through various standard techniques, including FTIR, FE-SEM, EDX, TEM, BET surface area analysis, XRD, and magnetic property determination using VSM. Next, the process parameters of wastewater treatment are statistically optimized, focusing on achieving a high level of COD (Chemical Oxygen Demand) removal as the response variable. The Fe3O4@AC nanocomposite's adsorption characteristics and kinetics are also assessed in detail. The remarkable outcome of this study is the successful application of the ternary hybrid technique, combining adsorption, Fenton process, and sonication. This approach proves highly effective, leading to nearly complete mineralization (or TOC removal) of the fertilizer industry wastewater. The results highlight the potential of the Fe3O4@AC nanocomposite and the ternary hybrid technique as a promising solution for tackling challenging wastewater pollutants from various chemical process industries. This paper reports investigations in the mineralization of industrial wastewater (COD = 3246 mg/L, TOC = 2500 mg/L) using a ternary (ultrasound + Fenton + adsorption) hybrid advanced oxidation process. Fe3O4 decorated activated charcoal (Fe3O4@AC) nanocomposites (surface area = 538.88 m2/g; adsorption capacity = 294.31 mg/g) were synthesized using co-precipitation. The wastewater treatment process was optimized using central composite statistical design. At optimum conditions, viz. pH = 4.2, H2O2 loading = 0.71 M, adsorbent dose = 0.34 g/L, reduction in COD and TOC of wastewater were 94.75% and 89%, respectively. This result results from synergistic interactions among the adsorption of pollutants onto activated charcoal and surface Fenton reactions induced due to the leaching of Fe2+/Fe3+ ions from the Fe3O4 nanoparticles. Micro-convection generated due to sonication assisted faster mass transport (adsorption/desorption) of pollutants between Fe3O4@AC nanocomposite and the solution. The net result of this synergism was high interactions and reactions among and radicals and pollutants that resulted in the effective mineralization of wastewater. The Fe3O4@AC showed excellent recovery (> 90 wt%) and reusability (> 90% COD removal) in 5 successive cycles of treatment. LC-MS analysis revealed effective (> 50%) degradation of more than 25 significant contaminants (in the form of herbicides and pesticides) after the treatment with ternary hybrid AOP. Similarly, the toxicity analysis test using the seed germination technique revealed ~ 60% reduction in the toxicity of the wastewater after treatment.

Keywords: chemical oxygen demand (cod), fe3o4@ac nanocomposite, kinetics, lc-ms, rsm, toxicity

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998 Arsenic Contamination in Drinking Water Is Associated with Dyslipidemia in Pregnancy

Authors: Begum Rokeya, Rahelee Zinnat, Fatema Jebunnesa, Israt Ara Hossain, A. Rahman

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Background and Aims: Arsenic in drinking water is a global environmental health problem, and the exposure may increase dyslipidemia and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of lipid metabolism, atherosclerosis formation, arsenic exposure and impact in pregnancy is still unclear. Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and Dyslipidemia. However, the exact mechanism of this arsenic-mediated increase in atherosclerosis risk factors remains enigmatic. We explore the association of the effect of arsenic on serum lipid profile in pregnant subjects. Methods: A total 200 pregnant mother screened in this study from arsenic exposed area. Our study group included 100 exposed subjects were cases and 100 Non exposed healthy pregnant were controls requited by a cross-sectional study. Clinical and anthropometric measurements were done by standard techniques. Lipidemic status was assessed by enzymatic endpoint method. Urinary As was measured by inductively coupled plasma-mass spectrometry and adjusted with specific gravity and Arsenic exposure was assessed by the level of urinary arsenic level > 100 μg/L was categorized as arsenic exposed and < 100 μg/L were categorized as non-exposed. Multivariate logistic regression and Student’s t - test was used for statistical analysis. Results: Systolic and diastolic blood pressure both were significantly higher in the Arsenic exposed pregnant subjects compared to the Non-exposed group (p<0.001). Arsenic exposed subjects had 2 times higher chance of developing hypertensive pregnancy (Odds Ratio 2.2). In parallel to the findings in Ar exposed subjects showed significantly higher proportion of triglyceride and total cholesterol and low density of lipo protein when compare to non- arsenic exposed pregnant subjects. Significant correlation of urinary arsenic level was also found with SBP, DBP, TG, T chol and serum LDL-Cholesterol. On multivariate logistic regression showed urinary arsenic had a positive association with DBP, SBP, Triglyceride and LDL-c. Conclusion: In conclusion, arsenic exposure may induce dyslipidemia like atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.

Keywords: Arsenic Exposure, Dyslipidemia, Gestational Diabetes Mellitus, Serum lipid profile

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997 The Determination of Pb and Zn Phytoremediation Potential and Effect of Interaction between Cadmium and Zinc on Metabolism of Buckwheat (Fagopyrum Esculentum)

Authors: Nurdan Olguncelik Kaplan, Aysen Akay

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Nowadays soil pollution has become a global problem. External added polluters to the soil are destroying and changing the structure of the soil and the problems are becoming more complex and in this sense the correction of these problems is going to be harder and more costly. Cadmium has got a fast mobility in the soil and plant system because of that cadmium can interfere very easily to the human and animal food chain and in the same time this can be very dangerous. The cadmium which is absorbed and stored by the plants is causing to many metabolic changes of the plants like; protein synthesis, nitrogen and carbohydrate metabolism, enzyme (nitrate reductase) activation, photo and chlorophyll synthesis. The biological function of cadmium is not known over the plants and it is not a necessary element. The plant is generally taking in small amounts the cadmium and this element is competing with the zinc. Cadmium is causing root damages. Buckwheat (Fagopyrum esculentum) is an important nutraceutical because of its high content of flavonoids, minerals and vitamins, and their nutritionally balanced amino-acid composition. Buckwheat has relatively high biomass productivity, is adapted to many areas of the world, and can flourish in sterile fields; therefore buckwheat plants are widely used for the phytoremediation process.The aim of this study were to evaluate the phytoremediation capacity of the high-yielding plant Buckwheat (Fagopyrum esculentum) in soils contaminated with Cd and Zn. The soils were applied to differrent doses cd(0-12.5-25-50-100 mg Cd kg−1 soil in the form of 3CdSO4.8H2O ) and Zn (0-10-30 mg Zn kg−1 soil in the form of ZnSO4.7H2O) and incubated about 60 days. Later buckwheat seeds were sown and grown for three mounth under greenhouse conditions. The test plants were irrigated by using pure water after the planting process. Buckwheat seeds (Gunes and Aktas species) were taken from Bahri Dagdas International Agricultural Research. After harvest, Cd and Zn concentrations of plant biomass and grain, yield and translocation factors (TFs) for Cd and Cd were determined. Cadmium accumulation in biomass and grain significantly increased in dose-dependent manner. Long term field trials are required to further investigate the potential of buckwheat to reclaimed the soil. But this could be undertaken in conjunction with actual remediation schemes. However, the differences in element accumulation among the genotypes were affected more by the properties of genotypes than by the soil properties. Gunes genotype accumulated higher lead than Aktas genotypes.

Keywords: buckwheat, cadmium, phytoremediation, zinc

Procedia PDF Downloads 417
996 Fatty Acid Translocase (Cd36), Energy Substrate Utilization, and Insulin Signaling in Brown Adipose Tissue in Spontaneously Hypertensive Rats

Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

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Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

Procedia PDF Downloads 139
995 The Transcription Factor HNF4a: A Key Player in Haematological Disorders

Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

Procedia PDF Downloads 95
994 Influence of Smoking on Fine And Ultrafine Air Pollution Pm in Their Pulmonary Genetic and Epigenetic Toxicity

Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

Procedia PDF Downloads 347
993 Isolation of Nitrosoguanidine Induced NaCl Tolerant Mutant of Spirulina platensis with Improved Growth and Phycocyanin Production

Authors: Apurva Gupta, Surendra Singh

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Spirulina spp., as a promising source of many commercially valuable products, is grown photo autotrophically in open ponds and raceways on a large scale. However, the economic exploitation in an open system seems to have been limited because of lack of multiple stress-tolerant strains. The present study aims to isolate a stable stress tolerant mutant of Spirulina platensis with improved growth rate and enhanced potential to produce its commercially valuable bioactive compounds. N-methyl-n'-nitro-n-nitrosoguanidine (NTG) at 250 μg/mL (concentration permitted 1% survival) was employed for chemical mutagenesis to generate random mutants and screened against NaCl. In a preliminary experiment, wild type S. platensis was treated with NaCl concentrations from 0.5-1.5 M to calculate its LC₅₀. Mutagenized colonies were then screened for tolerance at 0.8 M NaCl (LC₅₀), and the surviving colonies were designated as NaCl tolerant mutants of S. platensis. The mutant cells exhibited 1.5 times improved growth against NaCl stress as compared to the wild type strain in control conditions. This might be due to the ability of the mutant cells to protect its metabolic machinery against inhibitory effects of salt stress. Salt stress is known to adversely affect the rate of photosynthesis in cyanobacteria by causing degradation of the pigments. Interestingly, the mutant cells were able to protect its photosynthetic machinery and exhibited 4.23 and 1.72 times enhanced accumulation of Chl a and phycobiliproteins, respectively, which resulted in enhanced rate of photosynthesis (2.43 times) and respiration (1.38 times) against salt stress. Phycocyanin production in mutant cells was observed to enhance by 1.63 fold. Nitrogen metabolism plays a vital role in conferring halotolerance to cyanobacterial cells by influx of nitrate and efflux of Na+ ions from the cell. The NaCl tolerant mutant cells took up 2.29 times more nitrate as compared to the wild type and efficiently reduce it. Nitrate reductase and nitrite reductase activity in the mutant cells also improved by 2.45 and 2.31 times, respectively against salt stress. From these preliminary results, it could be deduced that enhanced nitrogen uptake and its efficient reduction might be a reason for adaptive and halotolerant behavior of the S. platensis mutant cells. Also, the NaCl tolerant mutant of S. platensis with significant improved growth and phycocyanin accumulation compared to the wild type can be commercially promising.

Keywords: chemical mutagenesis, NaCl tolerant mutant, nitrogen metabolism, photosynthetic machinery, phycocyanin

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992 Caffeic Acid in Cosmetic Formulations: An Innovative Assessment

Authors: Caroline M. Spagnol, Vera L. B. Isaac, Marcos A. Corrêa, Hérida R. N. Salgado

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Phenolic compounds are abundant in the Brazilian plant kingdom and they are part of a large and complex group of organic substances. Cinnamic acids are part of this group of organic compounds, and caffeic acid (CA) is one of its representatives. Antioxidants are compounds which act as free radical scavengers and, in other cases, such as metal chelators, both in the initiation stage and the propagation of oxidative process. The tyrosinase, polyphenol oxidase, is an enzyme that acts at various stages of melanin biosynthesis within the melanocytes and is considered a key molecule in this process. Some phenolic compounds exhibit inhibitory effects on melanogenesis by inhibiting the tyrosinase enzymatic activity and therefore has been the subject of studies. However, few studies have reported the effectiveness of these products and their safety. Objectives: To assess the inhibitory activity of tyrosinase, the antioxidant activity of CA and its cytotoxic potential. The method to evaluate the inhibitory activity of tyrosinase aims to assess the reduction transformation of L-dopa into dopaquinone reactions catalyzed by the enzyme. For evaluating the antioxidant activity was used the analytical methodology of DPPH radical inhibition. The cytotoxicity evaluation was carried out using the MTT method (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide), a colorimetric assay which determines the amount of insoluble violet crystals formed by the reduction of MTT in the mitochondria of living cells. Based on the results obtained during the study, CA has low activity as a depigmenting agent. However, it is a more potent antioxidant than ascorbic acid (AA), since a lower amount of CA is sufficient to inhibit 50% of DPPH radical. The results are promising since CA concentration that promoted 50% toxicity in HepG2 cells (IC50=781.8 μg/mL) is approximately 330 to 400 times greater than the concentration required to inhibit 50% of DPPH (IC50 DPPH= 2.39 μg/mL) and ABTS (IC50 ABTS= 1.96 μg/mL) radicals scavenging activity, respectively. The maximum concentration of caffeic acid tested (1140 mg /mL) did not reach 50% of cell death in HaCat cells. Thus, it was concluded that the caffeic acid does not cause toxicity in HepG2 and HaCat cells in the concentrations required to promote antioxidant activity in vitro, and it can be applied in topical products.

Keywords: caffeic acid, antioxidant, cytotoxicity, cosmetic

Procedia PDF Downloads 379
991 Acute and Subacute Toxicity of the Aqueous Extract of the Bark Stems of Balanites aegyptiaca (L.) Delile in Wistar Rats

Authors: Brahim Sow

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Background: Throughout West Africa, Balanites aegyptiaca (BA), or Zygophyllaceae, is widely used in traditional medicine to treat diabetes, hypertension, inflammation, malaria and liver disorders. In our recent research, we found that BA has nephroprotective potential against diabetes mellitus, hypertension and kidney disorders. However, to our knowledge, no systematic studies have been carried out on its derivative (toxicity) profile. Aim of the study: The study was conducted to assess the potential potency of the hydroalcoholic extract of BA bark in rats by the acute and sub-acute oral route. Materials and methods: Male and female rats in the acute depression study received BA extract orally at single doses of 500 mg/kg, 2000 mg/kg, 3000 mg/kg and 5000 mg/kg (n = 6 per group/sex). To assess acute depression, abnormal behaviour, toxic symptoms, weight and death were observed for 14 consecutive days. For the subacute impairment study, Wistar rats received the extract orally at doses of 125, 250 and 500 mg/kg (n=6 per group/sex) per day for 28 days. Behaviour and body weight were monitored daily. At the end of the treatment period, biochemical, haematological and histopathological examinations were performed, and gross and histopathological examinations of several organs were carried out. To determine the presence or absence of phytochemicals, the BA extract was subjected to gage phage chromatographic examination. Results: The absence of absorption chromatography of BA indicates the absence of cyanide groups. This suggests that the BA extract does not contain toxic substances. No mortality or adverse effects were observed at 5000 mg/kg in the acute depression test. With regard to body weight, general behaviour, relative organ weights, haematological and biochemical parameters, BA extract did not induce any mortality or potentially treatment-related effects in the sub-acute study. The normal architecture of the vital organs was revealed by histopathological examination, indicating the absence of morphological alterations. Conclusion: BA extract administered orally for 28 days at doses up to 500 mg/kg did not cause toxicological damage in rats in the present study. The median lethal dose (LD50) of the extract was estimated to be over 5000 mg/kg in an acute hyperglycaemia study.

Keywords: Balanites aegyptiaca L Delile, haematology, biochemistry, rat

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990 Factors Affecting Treatment Resilience in Patients with Oesophago-Gastric Cancers Undergoing Palliative Chemotherapy: A Literature Review

Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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989 Cadmium Levels in Patients with Type 2 Diabetes Mellitus in Thasala Southern Thailand

Authors: Supabhorn Yimthiang, Wiyada Khanwian

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Cadmium is a heavy metal that is important in the environment because it is highly toxic. The incidence and severity of type 2 diabetes mellitus are known to be associated with cadmium. The purpose of this study was to investigate the cadmium levels in patients with type 2 diabetes mellitus at diabetes mellitus clinic, Thasala hospital, Nakhon Si Thummarat, Thailand. The study population was composed of forty five subjects. Among them, twenty two were diabetic patients and twenty three were apparently healthy non-diabetic individual subjects. After an overnight fasting, blood and morning urine samples were collected from each subject to determine fasting blood sugar and cadmium levels in urine, respectively. Systolic and diastolic blood pressure values were measured by aneroid sphygmomanometer. Study approval was taken from the human subject ethics committee of Walailak University. Verbal and written informed consent was taken from all participants. In the study samples, there were 31.8% males and 68.2% females with mean age of 47+10.53 years. The geometric mean of urine cadmium was significantly higher in diabetic patients (1.015 + 0.79 µg/g creatinine) when compared with the healthy subjects (0.395 + 0.53 µg/g creatinine) (P<0.05). This result also showed that urine cadmium excretion in diabetic patients was higher than in healthy subjects by 2.6 times. Moreover, fasting blood sugar (153+47.86 μg/dl) and systolic blood pressure (183.26+17.15 mmHg) of diabetic patients was significantly different when compared with healthy subjects (79+5.38 μg/dl and 112.78+11.32 mmHg, respectively) (P<0.05). Meanwhile, the concentration of cadmium in urine showed positive correlation with fasting plasma glucose (r=0.616) and systolic blood pressure (r=0.487). This preliminary study showed that cadmium might play an important role in the development and pathogenesis of diabetes mellitus in general population. However, these findings require confirmation through additional epidemiological and biological research.

Keywords: blood pressure, cadmium, fasting blood sugar, type 2 diabetes mellitus

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988 Identification of Natural Liver X Receptor Agonists as the Treatments or Supplements for the Management of Alzheimer and Metabolic Diseases

Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

Procedia PDF Downloads 420
987 The Influence of Gender on Itraconazole Pharmacokinetic Parameters in Healthy Adults

Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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986 Efficient Hydrosilylation of Functionalized Alkenes via Heterogeneous Zinc Oxide Nanoparticle Catalysis

Authors: Ahlam Chennani, Nadia Anter, Abdelouahed Médaghri Alaoui, Abdellah Hannioui

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Non-precious metals such as zinc, copper, iron, and nickel are promising hydrosilylation catalysts due to their abundance, affordability, and low toxicity. This study focuses on the preparation of zinc nanoparticles using a simple, scalable method. Advanced techniques such as X-ray diffraction (XRD) and transmission electron microscopy (TEM) are used to characterize these catalysts, revealing their crystal structure and morphology. ZnO nanoparticles demonstrate high efficiency and selectivity in hydrosilylation reactions, producing silylated products. These results highlight the potential of ZnO nanocatalysts for advanced chemical transformations and practical applications in various industrial fields.

Keywords: nanoparticles, hydrosilylation, catalysts, non-precious metal

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985 Biogas Enhancement Using Iron Oxide Nanoparticles and Multi-Wall Carbon Nanotubes

Authors: John Justo Ambuchi, Zhaohan Zhang, Yujie Feng

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Quick development and usage of nanotechnology have resulted to massive use of various nanoparticles, such as iron oxide nanoparticles (IONPs) and multi-wall carbon nanotubes (MWCNTs). Thus, this study investigated the role of IONPs and MWCNTs in enhancing bioenergy recovery. Results show that IONPs at a concentration of 750 mg/L and MWCNTs at a concentration of 1500 mg/L induced faster substrate utilization and biogas production rates than the control. IONPs exhibited higher carbon oxygen demand (COD) removal efficiency than MWCNTs while on the contrary, MWCNT performance on biogas generation was remarkable than IONPs. Furthermore, scanning electron microscopy (SEM) investigation revealed extracellular polymeric substances (EPS) excretion from AGS had an interaction with nanoparticles. This interaction created a protective barrier to microbial consortia hence reducing their cytotoxicity. Microbial community analyses revealed genus predominance of bacteria of Anaerolineaceae and Longilinea. Their role in biodegradation of the substrate could have highly been boosted by nanoparticles. The archaea predominance of the genus level of Methanosaeta and Methanobacterium enhanced methanation process. The presence of bacteria of genus Geobacter was also reported. Their presence might have significantly contributed to direct interspecies electron transfer in the system. Exposure of AGS to nanoparticles promoted direct interspecies electron transfer among the anaerobic fermenting bacteria and their counterpart methanogens during the anaerobic digestion process. This results provide useful insightful information in understanding the response of microorganisms to IONPs and MWCNTs in the complex natural environment.

Keywords: anaerobic granular sludge, extracellular polymeric substances, iron oxide nanoparticles, multi-wall carbon nanotubes

Procedia PDF Downloads 293
984 T3P® -DMSO Mediated One-Pot Tandem Approach for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones/Thiones from Alcohols

Authors: Vinaya Kambappa

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Propylphosphonic anhydride (T3P®)-DMSO is used as an efficient and mild reagent for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones from aromatic alcohols. Alcohols are oxidized in situ to aldehydes under mild conditions, which in turn undergo a three-component reaction with β-ketoester and urea/thiourea to afford 3,4-dihydropyrimidin-2(1H)-ones/thiones. The synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones directly from alcohols has been reported for the first time best to our knowledge, under mild reaction conditions in good yield. The easy work-up procedure, low cost and less toxicity of the reagent are the main advantages of this protocol.

Keywords: β-ketoester, propylphosphonic anhydride, three-component reaction, pyrimidine

Procedia PDF Downloads 148
983 Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study

Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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