Search results for: liver spheroid

Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

Abstract:

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 97

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

Abstract:

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

Procedia PDF Downloads 183

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

Abstract:

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

Procedia PDF Downloads 304

Authors: Manisha, Manisha Mathur, Jay K. Desai, Shesh Asopa, Manisha Mehra

Abstract:

The present study was carried out for the comprehensive analysis of lumpy skin disease (LSD) in cattle and to elucidate the histopathology of vital organs in natural outbreaks. Lumpy skin disease (LSD) is a viral infection that primarily affects cattle. It is caused by a Capri pox virus and is characterized by the formation of skin nodules or lesions. For this study, a postmortem of 20 cows who died of Lumpy skin disease in different regions of Rajasthan was conducted. This study aimed to examine a cow's external and internal organs to confirm if lumpy skin disease was the cause of death. Accurate diagnosis is essential for improving disease surveillance, understanding the disease's progression, and informing control measures. Pathological examinations reveal virus-induced changes across organs, while histopathological analyses provide crucial insights into the disease's pathogenesis, aiding in the development of advanced diagnostics and effective prevention strategies. Histopathological examination of nodular skin lesions revealed edema, hyperemia, acanthosis, severe hydropic degeneration/ballooning degeneration, and hyperkeratosis in the epidermis. In the lungs, congestion, oedema, emphysema, and atelectasis were observed grossly. Microscopically changes were suggestive of interstitial pneumonia, suppurative pneumonia, bronchopneumonia post pneumonic fibrosis, and stage of resolution. Grossely liver showed congestion and necrotic foci microscopically in most of the cases, and the liver showed acute viral hepatitis. Microscopically in kidneys, multifocal interstitial nephritis was observed. There was marked interstitial inflammation and zonal fibrosis with cystically dilated tubules and bowman's capsules. Microscopically, most of the heart tissue section showed normal histology with few sarcocysts in between cardiac muscles. In some cases, loss of cross striation, sarcoplasmic vacuolation, fregmentation, and disintegration of cardiac fibres were observed. The present study revealed the characteristic gross and histopathological changes in different organs in natural cases of lumpy skin disease. Further, the disease was confirmed based on the molecular diagnosis and transmission electron microscopy of capripox infection in the affected cattle in the study area.

Keywords: Capripoxvirus, lumpy skin disease, polymerage chain reaction, transmission electron microscopy

Procedia PDF Downloads 25

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

Abstract:

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

Procedia PDF Downloads 280

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

Abstract:

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

Procedia PDF Downloads 252

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

Abstract:

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

Procedia PDF Downloads 443

Authors: Mustafa Metin Donma, Orkide Donma

Abstract:

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

Procedia PDF Downloads 198

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

Abstract:

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

Procedia PDF Downloads 628

Authors: Meli̇sa Aşci, Berk Kiliç, Emine Ulusoy

Abstract:

Ingestion of microplastics in humans has been increasing rapidly, as such hazardous materials are abundant in multiple food products, specifically milks. With increasing consumption rates, humans have been ingesting microplastics on a daily basis, making them prone to be intoxicated and even cause the disruption of intracellular pathways and liver cell disruption, and eventually tissue and organ damage. In this experiment, different milk types(animal-based and plant-based) were tested for microplastics. Results showed that animal-based milks contained a higher concentration of microplastics compared to plant-based milks. Research has shown that in addition to causing health issues in humans, microplastics can also affect livestock animals and plants.

Keywords: microplastics, plant-based milks, animal-based milks, preventive nutrition

Procedia PDF Downloads 28

Authors: Michelle Rippy

Abstract:

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

Procedia PDF Downloads 118

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

Abstract:

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

Procedia PDF Downloads 103

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

Procedia PDF Downloads 592

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

Abstract:

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

Procedia PDF Downloads 275

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

Abstract:

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 173

Authors: Antonina A. Shumakova, Sergey A. Khotimchenko

Abstract:

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

Procedia PDF Downloads 87

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 312

Authors: Salehi Zahabi Saleh, Rajabi Hosaien, Rasaneh Samira

Abstract:

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 320

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

Abstract:

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

Procedia PDF Downloads 504

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 296

Authors: Zakir Hossain, Md. Saddam Hossain

Abstract:

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 diet 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 basal or control (CON) diet and 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 (%), hepatosomatic 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 the control. Consequently, early embryonic and larval development was better in PBG treated group than in the 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: polyunsaturated fatty acids, beta glucan, maturity, immunity, catfish

Procedia PDF Downloads 7

Authors: Kakali Bhadra

Abstract:

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 G_o/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 209

Authors: Majid Afkhami, Maryam Ehsanpour, Zahra Khoshnood

Abstract:

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

Procedia PDF Downloads 660

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

Abstract:

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

Procedia PDF Downloads 78

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

Abstract:

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

Procedia PDF Downloads 322

Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

Abstract:

Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

Procedia PDF Downloads 234

Authors: T. Vijay Bhasker, N. K. S Gowda, P. Krishnamoorthy, D. T. Pal, A. K. Pattanaik, A. K. Verma

Abstract:

Boron (B) is a newer trace element and its biological importance and dietary essentiality is unclear in animals. The available literature suggests its putative role in bone mineralization, antioxidant status and steroid hormone synthesis. A feeding trial was conducted in Wister strain (Rattus norvegicus) albino rats for duration of 90 days. A total of 84 healthy weaned (3-4 weeks) experimental rats were randomly divided into 7 dietary groups (4 replicates of three each) viz., A (Basal diet/ Control), B (Basal diet + 5 ppm B), C (Basal diet + 10 ppm B), D (Basal diet + 20 ppm B), E (Basal diet + 40 ppm B), F (Basal diet-Ca 50%), G (Basal diet-Ca 50% + 40 ppm B). Dietary level of calcium (Ca) was maintained at two levels, 100% and 50% of requirement. Sodium borate was used as source of boron along with other ingredients of basal diet while preparing the pelletized diets. All the rats were kept in proper ventilated laboratory animal house maintained at temperature (23±2º C) and humidity (50 to 70%). At the end of experiment digestibility trial was conducted for 5 days to estimate nutrient digestibility and gut absorption of minerals. Eight rats from each group were sacrificed to collect the vital organs (liver, kidney and spleen) to study histopathology. Blood sample was drawn by heart puncture to determine biochemical profile. The average daily feed intake (g/rat/day), water intake (ml/rat/day) and body weight gain (g/rat/day) were similar among the dietary groups. The digestibility (%) of organic matter and crude fat were significantly improved (P < 0.05) was by B supplementation. The gut absorption (%) Ca was significantly increased (P < 0.01) in B supplemented groups compared to control. However, digestibility of dry matter and crude protein, gut absorption of magnesium and phosphorus showed a non-significant increasing trend with B supplementation. The gut absorption (%) of B (P < 0.01) was significantly lowered (P<0.05) in supplemented groups compared to un-supplemented ones. The serum level of triglycerides (mg/dL), HDL-cholesterol (mg/dL) and alanine transaminase (IU/L) were significantly lowered (P < 0.05) in B supplemented groups. While serum level of glucose (mg/dL) and alkaline phosphatase (KA units) showed a non-significant decreasing trend with B supplementation. However the serum levels of total cholesterol (mg/dL) and aspartate transaminase (IU/L) were similar among dietary groups. The histology sections of kidney and spleen revealed no significant changes among the dietary groups and were observed to be normal in anatomical architecture. However, the liver histology revealed cell degenerative changes with vacuolar degeneration and nuclear condensation in Ca deficient groups. But the comparative degenerative changes were mild in 40 ppm B supplemented Ca deficient group. In conclusion, dietary supplementation of graded levels of boron in rats had a positive effect on metabolism and health by improving nutrient digestibility and gut absorption of Ca. This indicates the beneficial role of dietary boron supplementation.

Keywords: boron, calcium, nutrient utilization, histopathology

Procedia PDF Downloads 318

Authors: Karen K. Perez-Ramirez, Genevieve Dupont, Virginia Gonzalez-Velez

Abstract:

Pancreatic alpha-cells participate on glucose regulation together with beta cells. They release glucagon hormone when glucose level is low to stimulate gluconeogenesis from the liver. As other excitable cells, alpha cells generate Ca2+ and metabolic oscillations when they are stimulated. It is known that the glucose level can trigger or silence this activity although it is not clear how this occurs in normal and diabetic people. In this work, we propose an electric-metabolic mathematical model implemented in Matlab to study the effect of different glucose levels on the electrical response and Ca2+ oscillations of an alpha cell. Our results show that Ca2+ oscillations appear in opposite phase with metabolic oscillations in a window of glucose values. The model also predicts a direct relationship between the level of glucose and the intracellular adenine nucleotides showing a self-regulating pathway for the alpha cell.

Keywords: Ca2+ oscillations, mathematical model, metabolic oscillations, pancreatic alpha cell

Procedia PDF Downloads 178

Authors: Aran Abd Al Rahman

Abstract:

Joubert syndrome regards as a congenital cerebellar ataxia caused by autosomal recessive carried on X chromosome. The disease diagnosed by brain imaging—the so-called molar tooth sign. Neurological signs were present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 30 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus, The purpose of our project was to detect the mutant gene (INPP5E gene) which cause Joubert syndrome. There were many methods used for diagnosis such as MRI and CT- scan and molecular diagnosis by doing ARMS PCR for detection of mutant gene that we were used in this research project. In this research for individual family which reported, the two children with parents, the two children were affected and were carrier.

Keywords: Joubert syndrome, genetic disease, Kurdistan region, Sulaimani

Procedia PDF Downloads 141

Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

Abstract:

Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

Procedia PDF Downloads 111