Search results for: liver biopsy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 928

Search results for: liver biopsy

478 Histopathological and Microbiological Studies on Subclinical Endometritis in Repeat Breeder Cow

Authors: Mehmet Akoz

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In this study the clinical, mikrobiological and histopathological diagnoses of subclinic and nonspecific endometritis resulting in repeat breeder. Total of 36 cows, aging between 3-9 years having normal oestrous cycles with no pregnancy following at least 3 unsuccesful inseminations, were used. Biopsy specimens for histopathological and swab for bacteri microbiological cultures were obtanied from endometrium of repeat breeders showing no macroskopic evidence of any defectiveness of genital organs and based on anamneses. Eleven out of 36 cows have positive bacteriological results. While 19 cows have varying degrees of and endometritis, the other 17 cows did not have any pathologic lesions. A total of 19 biopsies in 4 of the I. degree in endometritis, 9 of them II. degree endometritis and 6 were also III. degree endometritis was evaluated. In the majority of cows by the histopathological evaluation results (78.9%) monitored by the second and third-degree endometritis shape, in 83.3% of the isolated microorganisms were identified similar results. Histopathological and microbiological evaluation, along with clinical examination are important for the diagnoses and treatment of repeat breeders, having no resistance with well dissipation to endometrium rifaximina foam formulation was found to be more effective than PGF2α.

Keywords: repeat breeder, dairy cattle, histopathology, PGF2α, rifaximina

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477 Effects of Organic Chromium and Propylene Glycol on Milk Yield and Some Serum Biochemical Parameters of Early Lactation Dairy Cows

Authors: Cangir Uyarlar, Ismail Bayram, Ibrahim Sadi Cetingul, Mustafa Kabu, Eyup Eren Gultepe

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This study was conducted to determine the effects of organic chromium and organic chromium+propylene glycol on milk yield and some blood parameters related with liver fatty acid metabolism in early lactation dairy cows. Thirty multiparous Holstein dairy cows were used as study material. Cows assigned to three groups as control (C), chromium (Cr) and chromium+propylene glycol (CP). Live weight, parity and body condition score were used as covariates for statistical analyses. The study began at calving and finished at 3 weeks after calving. All cows were consumed same diet. Organic chromium and organic chromium+propylene glycol were orally administrated to cows in treatment groups shortly after the morning milking. Blood samples were collected from all cows on 0 (calving), 3rd, 6th, 9th, 12th, 15th, 18th, 21th days after calving. Then, samples were analyzed for BHBA (Betahydroxybutiric acids), NEFA (Non Esterified Fatty Acids), urea, total protein (TP) and glucose concentrations. Weekly milk yields were calculated from daily milk data on farm. Organic chromium treatment had no significant differences on serum biochemical parameters and milk yields. However, administration of organic chromium and propylene glycol combination decreased serum urea and total protein concentration, helped to protection from subclinical metabolic diseases via decreasing serum NEFA and BHBA concentrations. Also, this combination decreased serum glucose levels of cows. Neither only chromium nor chromium and propylene glycol combination did not affect milk yield throughout the study. These findings were suggested that orally administrations of chromium and propylene glycol combination improved liver glucose and fatty acid metabolism, decreased serum parameters which are representing subclinical diseases in early lactation dairy cows.

Keywords: chromium, early lactation dairy cows, propylene glycol, milk yield

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476 Nephrotoxicity and Hepatotoxicity Induced by Chronic Aluminium Exposure in Rats: Impact of Nutrients Combination versus Social Isolation and Protein Malnutrition

Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

Abstract:

Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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475 Idiopathic Gingival Fibromatosis

Authors: Bandana Koirala, Shivalal Sharma

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Introduction: Gingival enlargements are quite common and may be either inflammatory, non-inflammatory or a combination of both. Idiopathic gingival enlargement is a rare condition with a proliferative fibrous lesion of the gingival tissue that causes esthetic and functional problems. It is of undetermined etiology. Case Description: This case report addresses the diagnosis and treatment of a case of idiopathic gingival enlargement in a 9-year-old male patient. The patient presented with a generalized diffuse gingival enlargement involving the entire maxillary and the mandibular arch with extension on occlusal, buccal, lingual, and palatal surfaces with just parts of occlusal surfaces of few upper and lower molars visible resulting in open mouth, difficulty in mastication and speech. Biopsy report confirmed the diagnosis of fibromatosis gingivae. Gingivectomy was carried out in all four quadrants by using external bevel incision. Conclusion: Though total esthetics could not be restored due to unusual bony enlargement, the general appearance improved satisfactorily. Treatment after complete excision however, improved the masticatory competence to a great extent.

Keywords: idiopathic gingival fibromatosis, gingival enlargement, gingivectomy, medical and health sciences

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474 Effects of Oil Pollution on Euryglossa orientalis and Psettodes erumei in the Persian Gulf

Authors: Majid Afkhami, Maryam Ehsanpour, Reza Khoshnood, Zahra Khoshnood, Rastin Afkhami

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Marine pollution is a global environmental problem. Different human activities on land, in the water and in the air contribute to the contamination of seawater, sediments and organisms with potentially toxic substances. Contaminants can be natural substances or artificially produced compounds. After discharge into the sea, contaminants can stay in the water in dissolved form or they can be removed from the water column through sedimentation to the bottom sediments. Histopathological alterations can be used as indicators for the effects of various anthropogenic pollutants on organisms and are a reflection of the overall health of the entire population in the ecosystem. These histo pathological biomarkers are closely related to other biomarkers of stress since many pollutants have to undergo metabolic activation in order to be able to provoke cellular change in the affected organism. In order to make evaluation of the effects of oil pollution, some heavy metals bioaccumulation and explore their histopathological effects on hepatocytes of Oriental sole (Euryglossa orientalis) and Deep flounder (Psettodes erumei), fishes caught from two areas of north coast of the Persian Gulf: Bandar Abbass and Bandar Lengeh. Concentrations of Ni and V in liver of both species in two sampling regions were in following order: Bandar abbass Bandar lengeh; also between two species, these quantities were higher in P. erumei than E. orientalis in both sampling regions. Histopathology of the liver shows some cellular alterations including: degeneration, necrosis and tissue disruption, and histopathological effects were severe in P. erumei than E. orientalis. Results showed that Bandar Abbass region was more polluted than Bandar Lengeh, and because Ni and V were oil pollution indicators, and two flat fishes were benthic, they can receive considerable amount of oil pollution through their biological activities like feeding. Also higher amounts of heavy metal concentrations and major histopathological effects in E. orientalis showed strong relationship between benthic habitat of the fish and amounts of received pollutants from water and sediments, because E. orientalis is more related to the bottom than P. erumei.

Keywords: heavy metals, flatfishes, Persian Gulf, oil pollution

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473 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation

Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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472 Macroscopic Evaluation of the Effect of Low-Level Laser and Plasma Jet on Wound Healing in Rats

Authors: Zahra Tabarsi, Mehdi Marjani, Alireza Najafpour, Alborz Mirzade

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The aim of this study was to evaluate and compare the macroscopic effect of low level laser and plasma jet for wound healing in rats. The study was performed on 40 old male white rats with an average weight of 250 g and an average age of the same age. After preparing the rats from Ibn Sina Research Institute, they were kept the same for one week under environmental conditions such as temperature, humidity and light, and nutrition such as the type of diet and the number of meals. Then, to start the research, rats were randomly divided into two groups (A): laser treatment of wounds, group (B): plasma wound treatment. All rats were inhibited 4 hours before each anesthesia under conditions of abstinence and up to 2 hours after drinking water. Rats were anesthetized by intraperitoneal injection of ketamine 10% and xylazine 2%.After scrubbing between two shoulders of each rat, a circular wound was created by sterile 5 mm biopsy puncture. Group A rats were treated with low level laser in three sessions and group B in three sessions with argon plasma. Based on the observed results, it seems that Low level laser radiation has more acceptable and appropriate effects than cold plasma on the healing of rat skin wounds.

Keywords: low-level laser, plasma jet, rat, wound healing

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471 Quercetin Nanoparticles and Their Hypoglycemic Effect in a CD1 Mouse Model with Type 2 Diabetes Induced by Streptozotocin and a High-Fat and High-Sugar Diet

Authors: Adriana Garcia-Gurrola, Carlos Adrian Peña Natividad, Ana Laura Martinez Martinez, Alberto Abraham Escobar Puentes, Estefania Ochoa Ruiz, Aracely Serrano Medina, Abraham Wall Medrano, Simon Yobanny Reyes Lopez

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Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by elevated blood glucose levels. Quercetin is a natural flavonoid with a hypoglycemic effect, but reported data are inconsistent due mainly to the structural instability and low solubility of quercetin. Nanoencapsulation is a distinct strategy to overcome the intrinsic limitations of quercetin. Therefore, this work aims to develop a quercetin nano-formulation based on biopolymeric starch nanoparticles to enhance the release and hypoglycemic effect of quercetin in T2DM induced mice model. Starch-quercetin nanoparticles were synthesized using high-intensity ultrasonication, and structural and colloidal properties were determined by FTIR and DLS. For in vivo studies, CD1 male mice (n=25) were divided into five groups (n=5). T2DM was induced using a high-fat and high-sugar diet for 32 weeks and streptozotocin injection. Group 1 consisted of healthy mice fed with a normal diet and water ad libitum; Group 2 were diabetic mice treated with saline solution; Group 3 were diabetic mice treated with glibenclamide; Group 4 were diabetic mice treated with empty nanoparticles; and Group 5 was diabetic mice treated with quercetin nanoparticles. Quercetin nanoparticles had a hydrodynamic size of 232 ± 88.45 nm, a PDI of 0.310 ± 0.04 and a zeta potential of -4 ± 0.85 mV. The encapsulation efficiency of nanoparticles was 58 ± 3.33 %. No significant differences (p = > 0.05) were observed in biochemical parameters (lipids, insulin, and peptide C). Groups 3 and 5 showed a similar hypoglycemic effect, but quercetin nanoparticles showed a longer-lasting effect. Histopathological studies reveal that T2DM mice groups showed degenerated and fatty liver tissue; however, a treated group with quercetin nanoparticles showed liver tissue like that of the healthy mice group. These results demonstrate that quercetin nano-formulations based on starch nanoparticles are effective alternatives with hypoglycemic effects.

Keywords: quercetin, diabetes mellitus tipo 2, in vivo study, nanoparticles

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470 Identification and Characterization of in Vivo, in Vitro and Reactive Metabolites of Zorifertinib Using Liquid Chromatography Lon Trap Mass Spectrometry

Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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469 Surgical Collaboration in Managing Spinal Cord Compression Due to a Pre-Vertebral Chordoma: A Case Report

Authors: Rose Virginy S. Bautista, Ida Marie Tabangay-Lim, Helen Bongalon-Amo, Jose Modesto B. Abellera

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Chordomas, particularly those of the spine and the head and neck region, represent a rare and locally aggressive group of malignancies. The complexity of these tumors -given the rarity, location, and involvement of neurovascular structures- imposes a challenge in the diagnosis and management. We herein report a case of spinal cord compression due to a prevertebral cervical chordoma. The patient presented with a gradually enlarging lateral neck mass, with progressive bilateral extremity weakness and urinary incontinence; preoperative biopsy showed chordoma. A multidisciplinary approach for the management of this case was made, involving neurosurgery, head and neck surgery, and radiation oncology services. Surgical collaboration between the two cutting services was done to have a radical excision of the tumor and spinal cord decompression. The patient was then referred for adjuvant radiation therapy. With this collaborative treatment strategy, more comprehensive and quality care could be provided to our patients.

Keywords: chordoma, surgical collaboration, spinal cord compression, neurosurgery, head and neck surgery

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468 Ultrastructural Study of Surface Topography of Trematode Parasites of Domestic Buffalo (Bubalus bubalis) in Udaipur, India

Authors: Gayatri Swarnakar

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Paramphistomiasis and fascioliasis diseases have been prevalent due to presence of trematode parasites in the rumen and liver of domestic buffalo (Bubalus bubalis) in Udaipur, India. The trematode parasites such as Paramphistomum cervi, Gastrothylax crumenifer, Cotylophoron cotylophorum, Orthocoelium scoliocoelium, Fasciola hepatica and Fasciola gigantica were collected from infected rumen and liver of the freshly slaughtered buffaloes (Bubalus bubalis) at local zoo abattoir in Udaipur. Live trematodes were washed in normal saline, fixed in 0.2M cacodylate fixative, post fixed in osmium tetraoxide, dehydrated, dried, coated with gold sputter and observed under scanning electronic microscope (SEM). The surface tegument of Paramphistomum cervi was spineless with transverse folds, discontinuous with ridges and grooves. Two types of sensory papillae such as knob like and button shaped were also observed. The oral opening of Cotylophoron cotylophorum was surrounded by wrinkled and ridged tegument which formed concentric elevated rings. Tegument of Cotylophoron cotylophorum in acetabulum region was observed to be rough and bee-comb like structure. Genital sucker of this worm was surrounded by a tyre- shaped elevation of the tegument. Orthocoelium scoliocoelium showed circular and concentric rings of tegumental folds around the oral sucker. Genital pore had knob like papillae with radial tegumental folds. Surface topography of Fasciola gigantica and Fasciola hepatica were found to be rough due to occurrence of different types of spines, three types of sensory papillae, transverse folds and grooves. Oral and ventral suckers were spineless and covered with thick rims of transverse folds. Genital pore showed small scattered spines. Present research work would provide knowledge for ultrastructural characteristics of trematode parasites for chemotherapeutic measures and help us to evolve suitable strategy for the eradication of trematode parasites from the domestic buffalo (Bubalus bubalis).

Keywords: Domestic buffalo, tegument, trematode parasites, ultrastructure

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467 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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466 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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465 Comparative Analysis of Patent Protection between Health System and Enterprises in Shanghai, China

Authors: Na Li, Yunwei Zhang, Yuhong Niu

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The study discussed the patent protections of health system and enterprises in Shanghai. The comparisons of technical distribution and scopes of patent protections between Shanghai health system and enterprises were used by the methods of IPC classification, co-words analysis and visual social network. Results reflected a decreasing order within IPC A61 area, namely A61B, A61K, A61M, and A61F. A61B required to be further investigated. The highest authorized patents A61B17 of A61B of IPC A61 area was found. Within A61B17, fracture fixation, ligament reconstruction, cardiac surgery, and biopsy detection were regarded as common concerned fields by Shanghai health system and enterprises. However, compared with cardiac closure which Shanghai enterprises paid attention to, Shanghai health system was more inclined to blockages and hemostatic tools. The results also revealed that the scopes of patent protections of Shanghai enterprises were relatively centralized. Shanghai enterprises had a series of comprehensive strategies for protecting core patents. In contrast, Shanghai health system was considered to be lack of strategic patent protections for core patents.

Keywords: co-words analysis, IPC classification, patent protection, technical distribution

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464 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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463 The Biochemical and Radiographic Evaluation of the Non-Metastatic Bone Disease in Patients with Renal Cell Carcinoma Undergoing Hemodialysis

Authors: Aliakbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi

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Background: Bones are commonly affected by renal cell carcinoma (RCC) (primarily or secondary), and this condition causes bone fragility. The aim of this study was to evaluate the diagnostic value of noninvasive methods for the diagnosis of ROD in RCC patients on hemodialysis (HD) in northern Iran. Methods: In this cross-sectional study, 50 RCC patients with ESRD referred to dialysis units in northern Iran during 2021-2024 were randomly selected and investigated. The biochemical and radiographic evaluation of ROD and its subtypes was performed, and then all patients underwent bone biopsy and histopathological study, and finally, the diagnostic value of the noninvasive methods was assessed. Results: The mean age of patients was 58.9 ± 11.7 years, and 27 cases (54.0%) were female. 38 (76.0%) of RCC patients with ESRD had ROD, and 12 patients (24.0%) had no evidence of bone disorders. The sensitivity, specificity, positive and predictive values and accuracy of the noninvasive methods for the diagnosis of ROD were 92%, 82%, 95%, 75% and 90%, respectively. Conclusion: This study showed that the frequency of ROD in RCC patients with ESRD in northern Iran was high and the biochemical and radiographic markers have a high diagnostic value for ROD as well as histopathological assessment.

Keywords: renal cell carcinoma, renal osteodystrophy, hemodialysis, non-metastatic

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462 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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461 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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460 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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459 The Role of Cyfra 21-1 in Diagnosing Non Small Cell Lung Cancer (NSCLC)

Authors: H. J. T. Kevin Mozes, Dyah Purnamasari

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Background: Lung cancer accounted for the fourth most common cancer in Indonesia. 85% of all lung cancer cases are the Non-Small Cell Lung Cancer (NSCLC). The indistinct signs and symptoms of NSCLC sometimes lead to misdiagnosis. The gold standard assessment for the diagnosis of NSCLC is the histopathological biopsy, which is invasive. Cyfra 21-1 is a tumor marker, which can be found in the intermediate protein structure in the epitel. The accuracy of Cyfra 21-1 in diagnosing NSCLC is not yet known, so this report is made to seek the answer for the question above. Methods: Literature searching is done using online databases. Proquest and Pubmed are online databases being used in this report. Then, literature selection is done by excluding and including based on inclusion criterias and exclusion criterias. The selected literature is then being appraised using the criteria of validity, importance, and validity. Results: From six journals appraised, five of them are valid. Sensitivity value acquired from all five literature is ranging from 50-84.5 %, meanwhile the specificity is 87.8 %-94.4 %. Likelihood the ratio of all appraised literature is ranging from 5.09 -10.54, which categorized to Intermediate High. Conclusion: Serum Cyfra 21-1 is a sensitive and very specific tumor marker for diagnosis of non-small cell lung cancer (NSCLC).

Keywords: cyfra 21-1, diagnosis, nonsmall cell lung cancer, NSCLC, tumor marker

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458 Discriminant Function Based on Circulating Tumor Cells for Accurate Diagnosis of Metastatic Breast Cancer

Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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457 Approaches to Diagnosis of Ectopic Solid Organs in the Abdominopelvic Cavity

Authors: Van-Ngoc-Cuong Le, Ngoc-Quy Le

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Approaches to the diagnosis of ectopic solid organs in the abdominopelvic cavity include Accessory liver lobe, Accessory spleens (ectopic splenic tissue), Wandering spleen, Ectopic pancreatic tissue, Ectopic kidney (Pancake kidney), Cryptorchidism (undescended testis, ectopic testis), Ectopic endometriosis. The application of diagnostic imaging techniques, of which magnetic resonance imaging is the most important, includes a clinical case study and reports. Ectopic organs and tumors are easy to confuse. This is a concern, as well as practical challenges encountered and solutions adopted in the fields of Image Analysis.

Keywords: ectopic, accessory, wandering, tumor

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456 Metastatic Invasive Lobular Cancer Presenting as a Cervical Polyp

Authors: Sally Shepherd, Craig Murphy

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Introduction: The uterus or cervix are unusual locations as metastatic sites for cancers. It is further unusual for it to be a site of metastasis, whilst the primary malignancy remains occult. Case Report: A 63-year-old female with three months of altered bowel habits underwent a CT scan of the abdomen and pelvis, revealing a bulky uterus and left ovary, nonspecific colonic thickening, and diffuse peritoneal changes. She underwent colposcopy, which revealed a large endocervical polyp that was excised, revealing strongly hormone-positive metastatic invasive lobular breast cancer. She subsequently underwent a PET scan, which showed moderately diffuse activity in the cervix and left adnexa. Breast examination was unremarkable, and screening mammography, ultrasound, and MRI of the breast did not identify any lesions. Her blood tests revealed a Ca 15-3 of 934, CA-125 of 220, and CEA of 27. She was commenced on letrozole and ribociclib with an improvement in her symptoms. Conclusion: It is rare for occult breast cancer to be established and diagnosed by pelvic imaging and biopsy. Suspicion of uterine or cervical metastasis should be heightened in patients with an active or past history of breast cancer.

Keywords: occult breast cancer, cervical metastasis, invasive lobular carcinoma, metastasis

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455 CNS Cryptococcoma in an Immunocompetent Adult from a Low Resource Setting: A Case Report

Authors: Ssembatya Joseph Mary

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Introduction: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity as an opportunistic fungal infection. However, CNS cryptococcal granuloma (cryptococcoma) in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review the literature to illustrate the diagnosis and treatment of such lesions. Case presentation: A 62-year-old, HIV-negative, immunocompetent female patient with no known chronic illness presented with 5 months history of a progressive headache associated with on and off episodic generalized tonic-clonic convulsions. She had been to several hospitals before she was referred to our center with a diagnosis of a brain tumor. Before referral and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success. At Mbarara Regional Referral Hospital (MRRH), she had surgery with an excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery. Conclusion: The diagnosis of a parasitic CNS infection, particularly cryptococcal infection mimicking neoplastic lesions in an immunocompetent patient, was unusual. Surgical management of such lesions from different reports has a bad outcome and management remains totally conservative.

Keywords: Cryptococcal meningitis, immunocompetent patient, Uganda, low resource setting

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454 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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453 Analysis of Oral and Maxillofacial Histopathology Service in Tertiary Center in Oman in the Past 13 Years

Authors: Sabreen Al Shamli, Abdul Rahman Al azure

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Microscopic examination by histopathology is the gold standard for diagnosing many oral and maxillofacial pathologies. Current clinical guidelines and medicolegal regulations recommend the utilization of histopathology services for confirming pathologies being treated. The goal of this study was to determine the prevalence and distribution of oral and maxillofacial biopsies that had been histopathologically diagnosed at Anahdha Hospital (ANH). A total of 512 biopsies randomly selected from a ground total of 3310 biopsies, which were submitted for oral and maxillofacial histopathological specimens, were analyzed at Nahdha Hospital in Oman between January 2010 and December 2022. Data collected retrospectively selected from all case notes of patients who had oral histopathology examinations performed as part of their treatment. Data collected from the Shifa system was transferred to Microsoft Excel and analyzed using SPSS. Research ethics approval was obtained from the research committee of the hospital. This study provides background information on oral histopathology prevalence that could be helpful in future research in Oman. The findings of the present study are in agreement with the reported data from other investigations, even when it is taken into account how difficult it is to compare prevalence rates from different studies.

Keywords: oral biopsy, maxillofacial histopathology, oral disease, maxillofacial specimens

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452 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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451 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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450 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

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

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449 Histopatological Analysis of Vital Organs in Cattle Infected with Lumpy Skin Disease in Rajasthan, India

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

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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

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