Search results for: liver
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 729

Search results for: liver

369 Early Predictive Signs for Kasai Procedure Success

Authors: Medan Isaeva, Anna Degtyareva

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Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

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368 Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2 Alpha Metabolites in the Offspring of Rats with Streptozocin-Induced Diabetes

Authors: H. Y. Al-Matubsi, G. A. Oriquat, M. Abu-Samak, O. A. Al Hanbali, M. Salim

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Background: Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The aims of this study were to evaluate the protective effect of lipoic acid (LA) on fetal outcome and to elucidate changes that may be involved in the mechanism(s) implicit diabetic fetopathy. Methods: Female rats were rendered hyperglycemic using streptozocin and then mated with normal male rat. Pregnant non-diabetic (group1; n=9; and group2; n=7) or pregnant diabetic (group 3; n=10; and group 4; n=8) rats were treated daily with either lipoic acid (LA) (30 mg/kg body weight; groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure cyclooxygenases (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 (PGFM) levels. Maternal liver and plasma total glutathione levels were also determined. Results: Supplementation of diabetic rats with LA was found to significantly (P<0.05) reduce resorption rates in diabetic rats and increased mean fetal weight compared to diabetic group. Treatment of diabetic rats with LA leads to a significant (P<0.05) increase in liver and plasma total glutathione, in comparison with diabetic rats. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas and membranes were characteristic of experimental diabetic gestation associated with malformation. LA treatment to diabetic mothers failed to normalize levels of PGEM to the non-diabetic control rats. However, the levels of PGEM in malformed fetuses from LA-treated diabetic mothers was significantly (P < 0.05) higher than those in malformed fetuses from diabetic rats. Conclusions: We conclude that LA can reduce congenital malformations in the offspring of diabetic rats at day 15 of gestation. However, LA treatment did not completely prevent the occurrence of malformations, other factors, such as arachidonic acid deficiency and altered prostaglandin metabolismmay be involved in the pathogenesis of diabetes-induced congenital malformations.

Keywords: diabetes, lipoic acid, pregnancy, prostaglandins

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367 Ochratoxin-A in Traditional Meat Products from Croatian Households

Authors: Jelka Pleadin, Nina Kudumija, Ana Vulic, Manuela Zadravec, Tina Lesic, Mario Skrivanko, Irena Perkovic, Nada Vahcic

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Products of animal origin, such as meat and meat products, can contribute to human mycotoxins’ intake coming as a result of either indirect transfer from farm animals exposed to naturally contaminated grains and feed (carry-over effects) or direct contamination with moulds or naturally contaminated spice mixtures used in meat production. Ochratoxin A (OTA) is mycotoxin considered to be of the outermost importance from the public health standpoint in connection with meat products. The aim of this study was to investigate the occurrence of OTA in different traditional meat products circulating on Croatian markets during 2018, produced by a large number of households situated in eastern and north Croatian regions using a variety of technologies. Concentrations of OTA were determined in traditional meat products (n = 70), including dry fermented sausages (Slavonian kulen, Slavonian sausage, Istrian sausage and domestic sausage; n = 28), dry-cured meat products (pancetta, pork rack and ham; n = 22) and cooked sausages (liver sausages, black pudding sausages and pate; n = 20). OTA was analyzed by use of quantitative screening immunoassay method (ELISA) and confirmed for positive samples (higher than the limit of detection) by liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Whereas the bacon samples contaminated with OTA were not found, its level in dry fermented sausages ranged from 0.22 to 2.17 µg/kg and in dry-cured meat products from 0.47 to 5.35 µg/kg, with in total 9% of positive samples. Besides possible primary contamination of these products arising due to improper manufacturing or/and storage conditions, observed OTA contamination could also be the consequence of secondary contamination that comes as a result of contaminated feed the animals were fed on. OTA levels obtained in cooked sausages ranged from 0.32 to 4.12 µg/kg (5% of positives) and could probably be linked to the contaminated raw materials (liver, kidney and spices) used in the sausages production. The results showed an occasional OTA contamination of traditional meat products, pointing that to avoid such contamination on households these products should be produced and processed under standardized and well-controlled conditions. Further investigations should be performed in order to identify mycotoxin-producing moulds on the surface of the products and to define preventative measures that can reduce the contamination of traditional meat products during their production on households and period of storage.

Keywords: Croatian households, ochratoxin-A, traditional cooked sausages, traditional dry-cured meat products

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366 Chronic Hepatitis C Virus Screening: The Role, Strategies and Challenging of Primary Healthcare Faced to Augment and Identify Asymptomatic Infected Patients

Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

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Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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365 Effect of Dietary Organic Zinc Supplementation on Immunocompetance and Reproductive Performance in Rats

Authors: D. Nagalakshmi, S. Parashuramulu K. Sadasiva Rao, G. Aruna, L. Vikram

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The zinc (Zn) is the second most abundant trace element in mammals and birds, forming structural component of over 300 enzymes, playing an important role in anti-oxidant defense, immune response and reproduction. Organic trace minerals are more readily absorbed from the digestive tract and more biologically available compared with its inorganic salt. Thus, the present study was undertaken on 60 adult female Sprague Dawley rats (275±2.04 g) for experimental duration of 12 weeks to investigate the effect of dietary Zn supplementation from various organic sources on immunity, reproduction, oxidative defense mechanism and blood biochemical profile. The rats were randomly allotted to 30 replicates (2 per replicate) which were in turn randomly allotted to 5 dietary treatments varying in Zn source i.e., one inorganic source (Zn carbonate) and 4 organic sources (Zn-proteinate, Zn-propionate, Zn-amino acid complex and Zn-methionine) so as to supply NRC recommended Zn concentration (12 ppm Zn). Supplementation of organic Zn had no effect on various haematological and serum biochemical constituents compared to inorganic Zn fed rats. The TBARS and protein carbonyls concentration in liver indicative of oxidative stress was comparable between various organic and inorganic groups. The glutathione reductase activity in haemolysate (P<0.05) and reduced glutathione concentration in liver (P<0.01) was higher when fed organic Zn and RBC catalase activity was higher (P<0.01) on Zn methionine compared to other organic sources tested and the inorganic source. The humoral immune response assessed as antibody titres against sheep RBC was higher (P<0.05) when fed organic sources of zinc compared to inorganic source. The cell mediated immune response expressed as delayed type hypersensitivity reaction was higher (P<0.05) in rats fed Zn propionate with no effect of other organic Zn sources. The serum progesterone concentration was higher (P<0.05) in rats fed organic Zn sources compared to inorganic zinc. The data on ovarian folliculogenesis indicated that organic Zn supplementation increased (P<0.05) the number of graafian follicles and corpus luteum with no effect on primary, secondary and tertiary follicle number. The study indicated that rats fed organic sources of Zn had higher antioxidant enzyme activities, immune response and serum progesterone concentration with higher number of mature follicles. Though the effect of feeding various organic sources were comparable, rats fed zinc methionine had higher antioxidant activity and cell mediated immune response was higher in rats on Zn propionate.

Keywords: organic zinc, immune, rats, reproductive

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364 Microwave-Assisted Synthesis of a Class of Pyridine and Purine Thioglycoside Analogs

Authors: Mamdouh Abu-Zaied, K. Mohamed, Galal A. Nawwar

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Microwave-assisted synthesis of a new class of pyridine or purine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyridine 4-thiolate 4 and pyrazolo[1,5-a]pyrimidine-7-thiolate 5 derivatives via condensation of 1 with cyanoacetanilide derivative 2 or 5-aminopyrazole derivative 3 respectively under microwave irradiation, followed by coupling with halo sugars to give the corresponding pyridine and purine thioglycoside analogs. The obtained compounds were evaluated in vitro against lung (A549), colon (HCT116), liver (HEPG2), and MCF-7(breast) cancer cell lines. Some of them recorded promising activities.

Keywords: antitumor, cyclic sugars, pyrazoles, pyridines, pyrimidines, purines, thioglycosides

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363 Assessment of the Effect of Ethanolic Leaf Extract of Annona squamosa L. on Den Induced Hepatocellular Carcinoma in Experimental Animals

Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

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362 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

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361 Effect of Low Calorie Sweeteners on Chemical, Sensory Evaluation and Antidiabetic of Pumpkin Jam Fortified with Soybean

Authors: Amnah M. A. Alsuhaibani, Amal N. Al-Kuraieef

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Introduction: In the recent decades, production of low-calorie jams is needed for diabetics that comprise low calorie fruits and low calorie sweeteners. Object: the research aimed to prepare low calorie formulated pumpkin jams (fructose, stevia and aspartame) incorporated with soy bean and evaluate the jams through chemical analysis and sensory evaluation after storage for six month. Moreover, the possible effect of consumption of low calorie jams on diabetic rats was investigated. Methods: Five formulas of pumpkin jam with different sucrose, fructose, stevia and aspartame sweeteners and soy bean were prepared and stored at 10 oC for six month compared to ordinary pumpkin jam. Chemical composition and sensory evaluation of formulated jams were evaluated at zero time, 3 month and 6 month of storage. The best three acceptable pumpkin jams were taken for biological study on diabetic rats. Rats divided into group (1) served as negative control and streptozotocin induce diabetes four rat groups that were positive diabetic control (group2), rats fed on standard diet with 10% sucrose soybean jam, fructose soybean jam and stevia soybean jam (group 3, 4&5), respectively. Results: The content of protein, fat, ash and fiber were increased but carbohydrate was decreased in low calorie formulated pumpkin jams compared to ordinary jam. Production of aspartame soybean pumpkin jam had lower score of all sensory attributes compared to other jam then followed by stevia soybean Pumpkin jam. Using non nutritive sweeteners (stevia & aspartame) with soybean in processing jam could lower the score of the sensory attributes after storage for 3 and 6 months. The highest score was recorded for sucrose and fructose soybean jams followed by stevia soybean jam while aspartame soybean jam recorded the lowest score significantly. The biological evaluation showed a significant improvement in body weight and FER of rats after six weeks of consumption of standard diet with jams (Group 3,4&5) compared to Group1. Rats consumed 10% low calorie jam with nutrient sweetener (fructose) and non nutrient sweetener (stevia) soybean jam (group 4& 5) showed significant decrease in glucose level, liver function enzymes activity, and liver cholesterol & total lipids in addition of significant increase of insulin and glycogen compared to the levels of group 2. Conclusion: low calorie pumpkin jams can be prepared by low calorie sweeteners and soybean and also storage for 3 months at 10oC without change sensory attributes. Consumption of stevia pumpkin jam fortified with soybean had positive health effects on streptozoticin induced diabetes in rats.

Keywords: pumpkin jam, HFCS, aspartame, stevia, storage

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360 Identification of a Panel of Epigenetic Biomarkers for Early Detection of Hepatocellular Carcinoma in Blood of Individuals with Liver Cirrhosis

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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359 High-Performance Thin-layer Chromatography (HPTLC) Analysis of Multi-Ingredient Traditional Chinese Medicine Supplement

Authors: Martin Cai, Khadijah B. Hashim, Leng Leo, Edmund F. Tian

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Analysis of traditional Chinese medicinal (TCM) supplements has always been a laborious task, particularly in the case of multi‐ingredient formulations. Traditionally, herbal extracts are analysed using one or few markers compounds. In the recent years, however, pharmaceutical companies are introducing health supplements of TCM active ingredients to cater to the needs of consumers in the fast-paced society in this age. As such, new problems arise in the aspects of composition identification as well as quality analysis. In most cases of products or supplements formulated with multiple TCM herbs, the chemical composition, and nature of each raw material differs greatly from the others in the formulation. This results in a requirement for individual analytical processes in order to identify the marker compounds in the various botanicals. Thin-layer Chromatography (TLC) is a simple, cost effective, yet well-regarded method for the analysis of natural products, both as a Pharmacopeia-approved method for identification and authentication of herbs, and a great analytical tool for the discovery of chemical compositions in herbal extracts. Recent technical advances introduced High-Performance TLC (HPTLC) where, with the help of automated equipment and improvements on the chromatographic materials, both the quality and reproducibility are greatly improved, allowing for highly standardised analysis with greater details. Here we report an industrial consultancy project with ONI Global Pte Ltd for the analysis of LAC Liver Protector, a TCM formulation aimed at improving liver health. The aim of this study was to identify 4 key components of the supplement using HPTLC, following protocols derived from Chinese Pharmacopeia standards. By comparing the TLC profiles of the supplement to the extracts of the herbs reported in the label, this project proposes a simple and cost-effective analysis of the presence of the 4 marker compounds in the multi‐ingredient formulation by using 4 different HPTLC methods. With the increasing trend of small and medium-sized enterprises (SMEs) bringing natural products and health supplements into the market, it is crucial that the qualities of both raw materials and end products be well-assured for the protection of consumers. With the technology of HPTLC, science can be incorporated to help SMEs with their quality control, thereby ensuring product quality.

Keywords: traditional Chinese medicine supplement, high performance thin layer chromatography, active ingredients, product quality

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358 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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357 Comparing ITV Definitions From 4D CT-PET and Breath-Hold Technique with Abdominal Compression

Authors: R. D. Esposito, P. Dorado Rodriguez, D. Planes Meseguer

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In this work, we compare the contour of Internal Target Volume (ITV), for Stereotactic Body Radiation Therapy (SBRT) of a patient affected by a single liver metastasis, obtained from two different patient data acquisition techniques. The first technique consists in a free breathing Computer Tomography (CT) scan acquisition, followed by exhalation breath-hold and inhalation breath-hold CT scans, all of them applying abdominal compression while the second technique consists in a free breathing 4D CT-PET (Positron Emission Tomography) scan. Results obtained with these two methods are consistent, which demonstrate that at least for this specific case, both techniques are adequate for ITV contouring in SBRT treatments.

Keywords: 4D CT-PET, abdominal compression, ITV, SBRT

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356 Hematologic Inflammatory Markers and Inflammation-Related Hepatokines in Pediatric Obesity

Authors: Mustafa Metin Donma, Orkide Donma

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Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

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355 Contrast Enhanced Magnetic Resonance Angiography in Rats with Gadobenate Dimeglumine at 3T

Authors: Jao Jo-Chi, Chen Yen-Ku, Jaw Twei-Shiun, Chen Po-Chou

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This study aimed to investigate the magnetic resonance (MR) signal enhancement ratio (ER) of contrast-enhanced MR angiography (CE-MRA) in normal rats with gadobenate dimeglumine (Gd-BOPTA) using a clinical 3T scanner and an extremity coil. The relaxivities of Gd-BOPTA with saline only and with 4.5 % human serum albumin (HSA) were also measured. Compared with Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), Gd-BOPTA had higher relaxivities. The maximum ER of Aorta (ERa), kidney, liver and muscle with Gd-BOPTA were higher than those with Gd-DTPA. The maximum ERa appeared at 1.2 min and decayed to half at 10 min after Gd-BOPTA injection. This information is helpful for the design of CE-MRA study of rats.

Keywords: contrast-enhanced magnetic resonance angiography, Gd-BOPTA, Gd-DTPA, rat

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354 Time of Death Determination in Medicolegal Death Investigations

Authors: Michelle Rippy

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Medicolegal death investigation historically is a field that does not receive much research attention or advancement, as all of the subjects are deceased. Public health threats, drug epidemics and contagious diseases are typically recognized in decedents first, with thorough and accurate death investigations able to assist in epidemiology research and prevention programs. One vital component of medicolegal death investigation is determining the decedent’s time of death. An accurate time of death can assist in corroborating alibies, determining sequence of death in multiple casualty circumstances and provide vital facts in civil situations. Popular television portrays an unrealistic forensic ability to provide the exact time of death to the minute for someone found deceased with no witnesses present. The actuality of unattended decedent time of death determination can generally only be narrowed to a 4-6 hour window. In the mid- to late-20th century, liver temperatures were an invasive action taken by death investigators to determine the decedent’s core temperature. The core temperature was programmed into an equation to determine an approximate time of death. Due to many inconsistencies with the placement of the thermometer and other variables, the accuracy of the liver temperatures was dispelled and this once common place action lost scientific support. Currently, medicolegal death investigators utilize three major after death or post-mortem changes at a death scene. Many factors are considered in the subjective determination as to the time of death, including the cooling of the decedent, stiffness of the muscles, release of blood internally, clothing, ambient temperature, disease and recent exercise. Current research is utilizing non-invasive hospital grade tympanic thermometers to measure the temperature in the each of the decedent’s ears. This tool can be used at the scene and in conjunction with scene indicators may provide a more accurate time of death. The research is significant and important to investigations and can provide an area of accuracy to a historically inaccurate area, considerably improving criminal and civil death investigations. The goal of the research is to provide a scientific basis to unwitnessed deaths, instead of the art that the determination currently is. The research is currently in progress with expected termination in December 2018. There are currently 15 completed case studies with vital information including the ambient temperature, decedent height/weight/sex/age, layers of clothing, found position, if medical intervention occurred and if the death was witnessed. This data will be analyzed with the multiple variables studied and available for presentation in January 2019.

Keywords: algor mortis, forensic pathology, investigations, medicolegal, time of death, tympanic

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353 Examination of Calpurnia Aurea Seed Extract Activity Against Hematotoxicity and Hepatotoxicity in HAART Drug Induced Albino Wistar Rat

Authors: Haile Nega Mulata, Seifu Daniel, Umeta Melaku, Wendwesson Ergete, Natesan Gnanasekaran

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Background: In Ethiopia, medicinal plants have been used for various human and animal diseases. In this study, we have examined the potential effect of hydroethanolic extract of Calpurnia aurea seed against hepatotoxicity and haematotoxicity induced by Highly Active Antiretroviral Therapy (HAART) drugs in Albino Wistar rats. Methods: We collected Matured dried seeds of Calpurnia aurea from northern Ethiopia (south Tigray and south Gondar) in June 2013. The powder of the dried seed sample was macerated with 70% ethanol and dried using rotavapor. We have investigated the Preliminary phytochemical tests and in-vitro antioxidant properties. Then, we induced toxicity with HAART drugs and gave the experimental animals different doses of the crude extract orally for thirty-five days. On the 35th day, the animals were fasted overnight and sacrificed by cervical dislocation. We collected the blood samples by cardiac puncture. We excised the liver and brain tissues for further histopathological studies. Subsequently, we analysed serum levels of the liver enzymes- Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Total Bilirubin, and Serum Albumin, using commercial kits in Cobas Integra 400 Plus Roche Analyzer Germany. We have also assessed the haematological profile using an automated haematology Analyser (Sysmex KX-2IN). Results: A significant (P<0.05) decrease in serum enzymes (ALT and AST) and total bilirubin were observed in groups that received the highest dose (300mg/kg) of the seed extract. And significant (P<0.05) elevation of total red blood cell count, haemoglobin, and hematocrit percentage was observed in the groups that received the seed extract compared to the HAART-treated groups. The WBC count mean values showed a statistically significant increase (p<0.05) in groups that received HAART and 200 and 300mg/kg extract, respectively. The histopathological observations also showed that the oral administration of varying doses of the crude extract of the seed reversed to a normal state. Conclusion: The hydroethanolic extract of the Calpurnia aurea seed lowered the hepatotoxicity and haematotoxicity in a dose-dependent manner. The antioxidant properties of the Calpurnia aurea seed extract may have possible protective effects against the drug's toxicity.

Keywords: calpurnia aurea, hepatotoxicity, haematotoxicity, antioxidant, histopathology, HAART

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352 Therapeutic Management of Toxocara canis Induced Hepatitis in Dogs

Authors: Milind D. Meshram

Abstract:

Ascarids are the most frequent worm parasite of dogs and cats. There are two species that commonly infect dogs: Toxocara canis and Toxascaris leonina. Adult roundworms live in the stomach and intestines and can grow to 7 inches (18 cm) long. A female may lay 200,000 eggs in a day. The eggs are protected by a hard shell. They are extremely hardy and can live for months or years in the soil. A dog aged about 6 years, from Satara was referred to Teaching Veterinary Clinical Complex (TVCC) with a complaint of abdominal pain, anorexia, loss of condition and dull body coat with mucous pale membrane. The clinical examination revealed Anaemia, palpation of abdomen revealed enlargement of liver, slimy feel of the intestine loop, diarrhea.

Keywords: therapeutic management, Toxocara canis, induced hepatitis, dogs

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351 Homeostatic Analysis of the Integrated Insulin and Glucagon Signaling Network: Demonstration of Bistable Response in Catabolic and Anabolic States

Authors: Pramod Somvanshi, Manu Tomar, K. V. Venkatesh

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Insulin and glucagon are responsible for homeostasis of key plasma metabolites like glucose, amino acids and fatty acids in the blood plasma. These hormones act antagonistically to each other during the secretion and signaling stages. In the present work, we analyze the effect of macronutrients on the response from integrated insulin and glucagon signaling pathways. The insulin and glucagon pathways are connected by DAG (a calcium signaling component which is part of the glucagon signaling module) which activates PKC and inhibits IRS (insulin signaling component) constituting a crosstalk. AKT (insulin signaling component) inhibits cAMP (glucagon signaling component) through PDE3 forming the other crosstalk between the two signaling pathways. Physiological level of anabolism and catabolism is captured through a metric quantified by the activity levels of AKT and PKA in their phosphorylated states, which represent the insulin and glucagon signaling endpoints, respectively. Under resting and starving conditions, the phosphorylation metric represents homeostasis indicating a balance between the anabolic and catabolic activities in the tissues. The steady state analysis of the integrated network demonstrates the presence of a bistable response in the phosphorylation metric with respect to input plasma glucose levels. This indicates that two steady state conditions (one in the homeostatic zone and other in the anabolic zone) are possible for a given glucose concentration depending on the ON or OFF path. When glucose levels rise above normal, during post-meal conditions, the bistability is observed in the anabolic space denoting the dominance of the glycogenesis in liver. For glucose concentrations lower than the physiological levels, while exercising, metabolic response lies in the catabolic space denoting the prevalence of glycogenolysis in liver. The non-linear positive feedback of AKT on IRS in insulin signaling module of the network is the main cause of the bistable response. The span of bistability in the phosphorylation metric increases as plasma fatty acid and amino acid levels rise and eventually the response turns monostable and catabolic representing diabetic conditions. In the case of high fat or protein diet, fatty acids and amino acids have an inhibitory effect on the insulin signaling pathway by increasing the serine phosphorylation of IRS protein via the activation of PKC and S6K, respectively. Similar analysis was also performed with respect to input amino acid and fatty acid levels. This emergent property of bistability in the integrated network helps us understand why it becomes extremely difficult to treat obesity and diabetes when blood glucose level rises beyond a certain value.

Keywords: bistability, diabetes, feedback and crosstalk, obesity

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350 Ex-vivo Bio-distribution Studies of a Potential Lung Perfusion Agent

Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

Procedia PDF Downloads 142
349 Study of the Possibility of Adsorption of Heavy Metal Ions on the Surface of Engineered Nanoparticles

Authors: Antonina A. Shumakova, Sergey A. Khotimchenko

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The relevance of research is associated, on the one hand, with an ever-increasing volume of production and the expansion of the scope of application of engineered nanomaterials (ENMs), and on the other hand, with the lack of sufficient scientific information on the nature of the interactions of nanoparticles (NPs) with components of biogenic and abiogenic origin. In particular, studying the effect of ENMs (TiO2 NPs, SiO2 NPs, Al2O3 NPs, fullerenol) on the toxicometric characteristics of common contaminants such as lead and cadmium is an important hygienic task, given the high probability of their joint presence in food products. Data were obtained characterizing a multidirectional change in the toxicity of model toxicants when they are co-administered with various types of ENMs. One explanation for this fact is the difference in the adsorption capacity of ENMs, which was further studied in in vitro studies. For this, a method was proposed based on in vitro modeling of conditions simulating the environment of the small intestine. It should be noted that the obtained data are in good agreement with the results of in vivo experiments: - with the combined administration of lead and TiO2 NPs, there were no significant changes in the accumulation of lead in rat liver; in other organs (kidneys, spleen, testes and brain), the lead content was lower than in animals of the control group; - studying the combined effect of lead and Al2O3 NPs, a multiple and significant increase in the accumulation of lead in rat liver was observed with an increase in the dose of Al2O3 NPs. For other organs, the introduction of various doses of Al2O3 NPs did not significantly affect the bioaccumulation of lead; - with the combined administration of lead and SiO2 NPs in different doses, there was no increase in lead accumulation in all studied organs. Based on the data obtained, it can be assumed that at least three scenarios of the combined effects of ENMs and chemical contaminants on the body: - ENMs quite firmly bind contaminants in the gastrointestinal tract and such a complex becomes inaccessible (or inaccessible) for absorption; in this case, it can be expected that the toxicity of both ENMs and contaminants will decrease; - the complex formed in the gastrointestinal tract has partial solubility and can penetrate biological membranes and / or physiological barriers of the body; in this case, ENMs can play the role of a kind of conductor for contaminants and, thus, their penetration into the internal environment of the body increases, thereby increasing the toxicity of contaminants; - ENMs and contaminants do not interact with each other in any way, therefore the toxicity of each of them is determined only by its quantity and does not depend on the quantity of another component. Authors hypothesized that the degree of adsorption of various elements on the surface of ENMs may be a unique characteristic of their action, allowing a more accurate understanding of the processes occurring in a living organism.

Keywords: absorption, cadmium, engineered nanomaterials, lead

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348 Influence of Heliotropium Undulatum on Hepatic Glutathione Conjugating Enzymes System in Acetylhydrazide-Rats

Authors: S. Ameddah, O. Deffa, H. Aissaoui, A. Menad, R. Mekkiou, F. Benayache, S. Benayache

Abstract:

Acetylhydrazide (ACHD) is a metabolite of the anti-tubercular drug isoniazid (INH) that has been implicated in liver damage. This study was designed to evaluate hapatoprotective of n-BuOH extract of Heliotrpium undulatum (HUBE) in ACHD hepatotoxicity in rats. Hepatic damage was induced by administration of ACHD (300 mg/Kg op). The protection was affected by the administration of HUBE (200 mg/Kg op) for 14 days before ACHD administration, caused a decrease in LPO levels and in the transaminase and ALP levels and restored the GSH and its related enzymes (GPx, GST, GR) (50-62 %). Simultaneous administration of HUBE afforded a partial protection in statue of hepatic GSH conjugating enzymes upon administration of ACHD.

Keywords: heliotrpium undulatum, acetylhydrazide, glutathione conjugating enzymes, oxydatif stress, heaptoprotectif effect

Procedia PDF Downloads 283
347 Application of MRI in Radioembolization Imaging and Dosimetry

Authors: Salehi Zahabi Saleh, Rajabi Hosaien, Rasaneh Samira

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Yttrium-90 (90Y) radioembolisation(RE) is increasingly used for the treatment of patients with unresectable primary or metastatic liver tumours. Image-based approaches to assess microsphere distribution after RE have gained interest but are mostly hampered by the limited imaging possibilities of the Isotope 90Y. Quantitative 90Y-SPECT imaging has limited spatial resolution because it is based on 90Y Bremsstrahlung whereas 90Y-PET has better spatial resolution but low sensitivity. As a consequence, new alternative methods of visualizing the microspheres have been investigated, such as MR imaging of iron-labelled microspheres. It was also shown that MRI combines high sensitivity with high spatial and temporal resolution and with superior soft tissue contrast and thus can be used to cover a broad range of clinically interesting imaging parameters.The aim of the study in this article was to investigate the capability of MRI to measure the intrahepatic microsphere distribution in order to quantify the absorbed radiation dose in RE.

Keywords: radioembolisation, MRI, imaging, dosimetry

Procedia PDF Downloads 291
346 Acute Hepatotoxicity of Nano and Micro-Sized Iron Particles in Adult Albino Rats

Authors: Ghada Hasabo, Mahmoud Saber Elbasiouny, Mervat Abdelsalam, Sherin Ghaleb, Niveen Eldessouky

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In the near future, nanotechnology is envisaged for large scale use. Hence health and safety issues of nanoparticles should be promptly addressed. In the present study the acute hepatoxicity assessment due to high single oral dose of nano iron and micro iron particles were studied. The normal daily activities, biochemical alterations, blood coagulation, histopathological changes in Wister rats were the aspect of the toxicological assessment.This work found that significant alterations in biochemical enzymes (serum iron level, liver enzymes, albumin, and bilirubin levels), blood coagulation (PT, PC, INR), and histopathological changes occurred more prominently in the nano iron particle treated group.

Keywords: nanobiotechnology, nanosystems, nanomaterials, nanotechnology

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345 The Influence of Newest Generation Butyrate Combined with Acids, Medium Chain Fatty Acids and Plant Extract on the Performance and Physiological State of Laying Hens

Authors: Vilma Sasyte, Vilma Viliene, Asta Raceviciute-Stupeliene, Agila Dauksiene, Romas Gruzauskas, Virginijus Slausgalvis, Jamal Al-Saifi

Abstract:

The aim of the present study was to investigate the effect of butyrate, acids, medium-chain fatty acids and plant extract mixture on performance, blood and gastrointestinal tract characteristics of laying hens’. For the period of 8 weeks, 24 Hisex Brown laying hens were randomly assigned to 2 dietary treatments: 1) control wheat-corn-soybean meal based diet (Control group), 2) control diet supplemented with the mixture of butyrate, acids, medium chain fatty acids and plant extract (Lumance®) at the level of 1.5 g/kg of feed (Experimental group). Hens were fed with a crumbled diet at 125 g per day. Housing and feeding conditions were the same for all groups and met the requirements of growth for laying hens of Hisex Brown strain. In the blood serum total protein, bilirubin, cholesterol, DTL- and MTL- cholesterol, triglycerides, glucose, GGT, GOT, GPT, alkaline phosphatase, alpha amylase, contents of c-reactive protein, uric acid, and lipase were analyzed. Development of intestines and internal organs (intestinal length, intestinal weight, the weight of glandular and muscular stomach, pancreas, heart, and liver) were determined. The concentration of short chain fatty acids in caecal content was measured using the method of HPLC. The results of the present study showed that 1.5 g/kg supplementation of feed additive affected egg production and feed conversion ratio for the production of 1 kg of egg mass. Dietary supplementation of analyzed additive in the diets increased the concentration of triglycerides, GOT, alkaline phosphatase and decreased uric acid content compared with the control group (P<0.05). No significant difference for others blood indices in comparison to the control was observed. The addition of feed additives in laying hens’ diets increased intestinal weight by 11% and liver weight by 14% compared with the control group (P<0.05). The short chain fatty acids (propionic, acetic and butyric acids) in the caecum of laying hens in experimental groups decreased compared with the control group. The supplementation of the mixture of butyrate, acids, medium-chain fatty acids and plant extract at the level of 1.5 g/kg in the laying hens’ diets had the effect on the performance, some gastrointestinal tract function and blood parameters of laying hens.

Keywords: acids, butyrate, laying hens, MCFA, performance, plant extract, psysiological state

Procedia PDF Downloads 271
344 Apoptotic Induction Ability of Harmalol and Its Binding: Biochemical and Biophysical Perspectives

Authors: Kakali Bhadra

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Harmalol administration caused remarkable reduction in proliferation of HepG2 cells with GI50 of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG2 cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub Go/G1 population made the cancer cell, HepG2, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

Procedia PDF Downloads 186
343 Determination of Heavy Metals (Cd, Pb, Hg, Cu, Fe, Mn, Al, As, Ni and Zn) in 6 Important Commercial Fish Species in North of Hormoz Strait

Authors: Majid Afkhami, Maryam Ehsanpour, Zahra Khoshnood

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The concentrations of 10 heavy metals (Cd, Pb, Hg, Cu, Fe, Mn, Al, As, Ni, Zn) were measured in muscle, gill and liver of 6 species from Hormoz Strait in north coast of Persian Gulf in 12 months (April 2009 – March 2010). All samples were analyzed three times for Cd, Pb, Cu, Fe, Mn, Al, As, Ni, Zn by inductively coupled plasma-atomic emission spectrometry (ICP-AES) and for Hg by LECO AMA254 Advanced Mercury Analyzer. Results of this study showed that iron had the highest concentration (total mean concentration) in all species, followed by Zn, Cu, Ni, Al, Pb, Mn, Cd, Hg and lowest concentration in three tissues was As. In addition, the accumulation of metals was species-dependent, and was higher in Scomberomorous commerson and Scomberomorous guttatus (p<0.05) and the lowest concentration was record in Pampus argenteus (p<0.05).

Keywords: Persian Gulf, heavy metals, Hormoz strait, Scomberomorous guttatus, Scomberomorous commerson, Pampus argenteus

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342 Effects of Dietary Polyunsaturated Fatty Acids and Beta Glucan on Maturity, Immunity, and Fry Quality of Pabdah Catfish, Ompok pabda

Authors: Zakir Hossain, Saddam Hossain

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A nutritionally balanced diet and selection of appropriate species are important criteria in aquaculture. The present study was conducted to evaluate the effects of polyunsaturated fatty acids (PUFAs) and beta glucan-containing diets on growth performance, feed utilization, maturation, immunity, early embryonic and larval development of endangered Pabdah catfish, Ompok pabda. In this study, squid extracted lipids and mushroom powder were used as the source of PUFAs and beta-glucan, respectively, and formulated two isonitrogenous diets such as a basal or control (CON) diet and a treated (PBG) diet with maintaining 30% protein levels. During the study period, similar physicochemical conditions of water such as temperature, pH, and dissolved oxygen (DO) were 26.5±2 °C, 7.4±0.2, and 6.7±0.5 ppm, respectively, in each cistern. The results showed that final mean body weight, final mean length gain, food conversion ratio (FCR), specific growth rate (SGR), food conversion efficiency (%), hepato somatic index (HSI), kidney index (KI), and viscerosomatic index (VSI) were significantly (P<0.01 and P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet. The length-weight relationship and relative condition factor (K) of O. pabda were significantly (P<0.05) affected by the PBG diet. The gonadosomatic index (GSI), sperm viability, blood serum calcium ion concentrations (Ca²⁺), and vitellogenin level were significantly (P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet; which was used to the indication of fish maturation. During the spawning season, lipid granules and normal morphological structure were observed in the treated fish liver, whereas fewer lipid granules of liver were observed in the control group. Based on the immunity and stress resistance-related parameters such as hematological indices, antioxidant activity, lysozyme level, respiratory burst activity, blood reactive oxygen species (ROS), complement activity (ACH50 assay), specific IgM, brain AChE, plasma PGOT, and PGPT enzyme activity were significantly (P<0.01 and P<0.05) higher in fish fed the PBG diet than that of fish fed the CON diet. The fecundity, fertilization rate (92.23±2.69%), hatching rate (87.43±2.17 %), and survival (76.62±0.82%) of offspring were significantly higher (P˂0.05) in the PBG diet than in control. Consequently, early embryonic and larval development was better in PBG treated group than in control. Therefore, the present study showed that the polyunsaturated fatty acids (PUFAs) and beta-glucan enriched experimental diet were more effective and achieved better growth, feed utilization, maturation, immunity, and spawning performances of O. pabda.

Keywords: lipids, beta-glucan, fish maturity, fish immunity

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341 Evaluation of Ocular Changes in Hypertensive Disorders of Pregnancy

Authors: Rajender Singh, Nidhi Sharma, Aastha Chauhan, Meenakshi Barsaul, Jyoti Deswal, Chetan Chhikara

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Introduction: Pre-eclampsia and eclampsia are hypertensive disorders of pregnancy with multisystem involvement and are common causes of morbidity and mortality in obstetrics. It is believed that changes in retinal arterioles may indicate similar changes in the placenta. Therefore, this study was undertaken to evaluate the ocular manifestations in cases of pre-eclampsia and eclampsia and to deduce any association between the retinal changes and blood pressure, the severity of disease, gravidity, proteinuria, and other lab parameters so that a better approach could be devised to ensure maternal and fetal well-being. Materials and Methods: This was a hospital-based cross-sectional study conducted over a period of one year, from April 2021 to May 2022. 350 admitted patients with diagnosed pre-eclampsia, eclampsia, and pre-eclampsia superimposed on chronic hypertension were included in the study. A pre-structured proforma was used. After taking consent and ocular history, a bedside examination to record visual acuity, pupillary size, corneal curvature, field of vision, and intraocular pressure was done. Dilated fundus examination was done with a direct and indirect ophthalmoscope. Age, parity, BP, proteinuria, platelet count, liver and kidney function tests were noted down. The patients with positive findings only were followed up after 72 hours and 6 weeks of termination of pregnancy. Results: The mean age of patients was 26.18±4.33 years (range 18-39 years).157 (44.9%) were primigravida while 193(55.1%) were multigravida.53 (15.1%) patients had eclampsia, 128(36.5%) had mild pre-eclampsia,128(36.5%) had severe pre-eclampsia and 41(11.7%) had chronic hypertension with superimposed pre-eclampsia. Retinal changes were found in 208 patients (59.42%), and grade I changes were the most common. 82(23.14%) patients had grade I changes, 75 (21.4%) had grade II changes, 41(11.71%) had grade III changes, and 11(3.14%) had serous retinal detachment/grade IV changes. 36 patients had unaided visual acuity <6/9, of these 17 had refractive error and 19(5.4%) had varying degrees of retinal changes. 3(0.85%) out of 350 patients had an abnormal field of vision in both eyes. All 3 of them had eclampsia and bilateral exudative retinal detachment. At day 4, retinopathy in 10 patients resolved, and 3 patients had improvement in visual acuity. At 6 weeks, retinopathy in all the patients resolved spontaneously except persistence of grade II changes in 23 patients with chronic hypertension with superimposed pre-eclampsia, while visual acuity and field of vision returned to normal in all patients. Pupillary size, intraocular pressure, and corneal curvature were found to be within normal limits at all times of examination. There was a statistically significant positive association between retinal changes and mean arterial pressure. The study showed a positive correlation between fundus findings and severity of disease (p value<0.05) and mean arterial pressure (p value<0.005). Primigravida had more retinal changes than multigravida patients. A significant association was found between fundus changes and thrombocytopenia and deranged liver and kidney function tests (p value<0.005). Conclusion: As the severity of pre-eclampsia and eclampsia increases, the incidence of retinopathy also increases, and it affects visual acuity and visual fields of the patients. Thus, timely ocular examination should be done in all such cases to prevent complications.

Keywords: eclampsia, hypertensive, ocular, pre-eclampsia

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340 The Differences between Direct Examination and ELISA Test during the Diagnosis of Fasciolosis in Jaundiced Slaughtered Sheep in Iraq

Authors: Azad A. Meerkhan, Alaa Hani Razak, Bayan M. S. Younis

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The efficiency of enzyme-linked immunosorbent assay (ELISA) in sheep infected with Fasciola hepatica was studied. 232 jaundiced sheep among 5208 sheep slaughter in the Duhok abattoir (regardless of the age and gender) between the period of May. 2012 to Oct. 2012 were examined by direct examination (Searching of adult flukes in the bile duct) and by Enzyme-linked immunosorbent assay (ELISA) to detect the prevalence of fascioliasis in the studied population which showed a high observed infection ratio in Sep. 2012 (12.2%) with the high (ELISA) result of infection in May. 2012 (25.36%). Significant differences were found between the two ways in all of the months with the highest difference in May. 2012 and the net deference between the both ways was 6.91%.

Keywords: fascioliasis, Fasciola hepatica, layers, liver fluk, ELISA, direct examination

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