Search results for: liver transplant candidates

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

Procedia PDF Downloads 271

Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

Abstract:

Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

Procedia PDF Downloads 431

Authors: Emre Ipekci Cetin, Ebru Tarcan Icigen

Abstract:

Personnel selection process is considered as one of the most important and most difficult issues in human resources management. At the stage of personnel selection, the applicants are handled according to certain criteria, the candidates are dealt with, and efforts are made to select the most appropriate candidate. However, this process can be more complicated in terms of the managers who will carry out the staff selection process. Candidates should be evaluated according to different criteria such as work experience, education, foreign language level etc. It is crucial that a rational selection process is carried out by considering all the criteria in an integrated structure. In this study, the problem of choosing the front office manager of a 5 star accommodation enterprise operating in Antalya is addressed by using multi-criteria decision-making methods. In this context, SWARA (Step-wise weight assessment ratio analysis) and MOORA (Multi-Objective Optimization on the basis of ratio analysis) methods, which have relatively few applications when compared with other methods, have been used together. Firstly SWARA method was used to calculate the weights of the criteria and subcriteria that were determined by the business. After the weights of the criteria were obtained, the MOORA method was used to rank the candidates using the ratio system and the reference point approach. Recruitment processes differ from sector to sector, from operation to operation. There are a number of criteria that must be taken into consideration by businesses in accordance with the structure of each sector. It is of utmost importance that all candidates are evaluated objectively in the framework of these criteria, after these criteria have been carefully selected in the selection of suitable candidates for employment. In the study, staff selection process was handled by using SWARA and MOORA methods together.

Keywords: accommodation establishments, human resource management, multi-objective optimization on the basis of ratio analysis, multi-criteria decision making, step-wise weight assessment ratio analysis

Procedia PDF Downloads 343

Authors: Toumi Farah, Charallah Salima

Abstract:

In the Algerian Sahara, goat farming is predominant, and it’s associated with other types of breeding, particularly camel and sheep; it also constitutes a significant proportion of breeding exclusively goat. This Saharan goat is a small ruminant with a black dress with white’s spots, hanging ears, and a coat more or less long. It is known for its hardiness and resistance to adverse conditions of arid zones and its perfect ecophysiological adaptation to harsh environmental conditions. However, pregnancy alterations, particularly abortion, degrade its productivity and cause economic losses, having both direct and indirect effects on animal production, like the costs of veterinary interventions and the reconstitution of livestock. The purpose of this work is to study the histological aspect of the liver of goats’ aborted living under nomadic herds in the region of Béni-Abbès (30° 7' N, 2° 10 'O). The organs were collected in physiological serum, rinsed, and then fixed with formaldehyde (37°, diluted at 10%). After that, these samples were processed for a topographic study. The morphometric study of the liver was performed by using an image analysis and processing software "Image J"; the various measurements obtained are intended to specify the supposed stage of development according to the body weight. The histological structure of the liver shows that the hepatic parenchyma consists of vascular conjunctive spaces surrounded by Glisson’s capsule. The sinusoids and hepatic portal vein are full of red blood cells, representing sinusoidal congestion and a thrombosed vein. At high magnification, the blood vessels show the presence of vascular thrombosis and haemorrhage in some areas of the hepatic parenchyma. Morphometric analysis shows that the number of liver parenchymal cells and the diameter of liver vessels vary according to the stage of development. The results obtained will provide details of the anatomical and cellular elements that can be used in the diagnosis of early or late abortion and late embryonic death. It would be interesting to find, by immunohistochemistry, some inflammatory markers useful for monitoring the progress of pregnancy and bioindicators of fetomaternal distress.

Keywords: aborting goat, arid zone, liver, histopathology

Procedia PDF Downloads 98

Authors: Jichan Jang

Abstract:

Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. In this study, we screened the library to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indication of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Thus, we found that compound X, identified, may be a promising candidate in the M. abscessus drug discovery pipeline.

Keywords: Mycobacterium abscessus, antibiotics, drug discovery, emerging Pathogen

Procedia PDF Downloads 209

Authors: Anjana Aggarwal, Sheilja Walia

Abstract:

Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

Procedia PDF Downloads 84

Authors: Deepak Nathiya1, Ramesh Roop Rai, Pratima Singh1, Preeti Raj1, Supriya Suman, Balvir Singh Tomar

Abstract:

Background: Sarcopenia is a catabolic state in liver cirrhosis (LC), accelerated with a breakdown of skeletal muscle to release amino acids which adversely affects survival, health-related quality of life, and response to any underlying disease. The primary objective of the study was to investigate the long-term effect of branched-chain amino acids (BCAA) supplementations on parameters associated with improved prognosis in sarcopenic patients with LC, as well as to evaluate its impact on cirrhotic-related events. Methods: We carried out a 24 week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention trial comparing the efficacy of BCAA against lactoalbumin (L-ALB) on 106 sarcopenic liver cirrhotics. The BCAA (intervention) group was treated with 7.2 g BCAA per whereas, the lactoalbumin group was also given 6.3 g of L-Albumin. The primary outcome was to assess the impact of BCAA on parameters of sarcopenia: muscle mass, muscle strength, and physical performance. The secondary outcomes were to study combined survival and maintenance of liver function changes in laboratory and clinical markers in the duration of six months. Results: Treatment with BCAA leads to significant improvement in sarcopenic parameters: muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. Prognostic markers also improved significantly in the study. Conclusion: The current clinical trial demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced liver cirrhosis.

Keywords: sarcopenia, liver cirrhosis, BCAA, quality of life

Procedia PDF Downloads 136

Authors: Sabika Rafiq, Rubaida Mehmood, Sajid Hussain, Atia Iqbal

Abstract:

Background and objectives: The pathogenesis of liver function abnormalities and cardiac dysfunction in hyperthyroid patients after I131 treatment is still unclear. This study aimed to determine the effects of radioiodine I131 on liver function parameters, lactate dehydrogenase (LDH) and low-density lipoproteins (LDL) before and after I131 therapy hyperthyroidism patients. Material & Methods: A total of 52 patients of hyperthyroidism recommended for I131were involved in this study with ages ranging from 12–65 years (mean age=38.6±14.8 & BMI=11.5±3.7). The significance of the differences between the results of 1st, 2nd and 3rd-time serum analysis was assessed by unpaired student’s t-test. Associations between the parameters were assessed by Spearman correlation analysis. Results: Significant variations were observed for thyroid profile free FT3 (p=0.04), FT4 (p=0.01), TSH (p=0.005) during the follow-up treatment. Before taking I131 (serum analyzed at 1st time), negative correlation of FT3 with AST (r=-0.458, p=0.032) and LDL (r=-0.454, p=0.039) were observed. During 2nd time (after stopping carbimazole), no correlation was assessed. Two months after the administration of I131 drops, a significant negative association of FT3 (r=-0.62, p=0.04) and FT4(r=-0.61, p=0.02) with ALB were observed. FT3(r=-0.82, p=0.00) & FT4 (r=-0.71, p=0.00) also showed negative correlation with LDL after I131 therapy. Whereas TSH showed significant positive association with ALB (r=0.61, p=0.01) and LDL (r=0.70, p=0.00) respectively. Conclusion: Current findings suggested that the association of TFTs with biochemical parameters in patients with goiter recommended for iodine therapy is an important diagnostic and therapeutic tool. The significant changes increased in transaminases and low-density lipoprotein levels after taking I131drops are alarming signs for heart and liver function abnormalities and warrant physicians' attention on an urgent basis.

Keywords: hyperthyroidism, carbimazole, radioiodine I131, liver functions, low-density lipoprotein

Procedia PDF Downloads 155

Authors: Azadeh Mottaghi, Reyhaneh Yousefi, Saeed Safari

Abstract:

Background: Bariatric surgery is widely proposed as the most effective approach to mitigate the growing pace of morbid obesity. As bariatric surgery candidates suffer from pre-existing nutritional deficiencies, it is of great importance to assess nutritional status of candidates before surgery in order to establish appropriate nutritional interventions. Objectives: The present study assessed and represented baseline data according to the nutritional status among candidates for bariatric surgery. Methods: A cross-sectional analysis of pre-surgery data was collected on 170 morbidly obese patients undergoing bariatric surgery between October 2017 and February 2018. Dietary intake data (evaluated through 147-item food frequency questionnaire), anthropometric measures and biochemical parameters were assessed. Results: Participants included 145 females (25 males) with average age of 37.3 ± 10.2 years, BMI of 45.7 ± 6.4 kg/m² and reported to have a total of 72.3 ± 22.2 kg excess body weight. The most common nutritional deficiencies referred to iron, ferritin, transferrin, albumin, vitamin B12, and vitamin D, the prevalence of which in the study population were as followed; 6.5, 6.5, 3, 2, 17.6 and 66%, respectively. Mean energy, protein, fat, and carbohydrate intake were 3887.3 ± 1748.32 kcal/day, 121.6 ± 57.1, 144.1 ± 83.05, and 552.4 ± 240.5 gr/day, respectively. The study population consumed lower levels of iron, calcium, folic acid, and vitamin B12 compared to the Dietary Reference Intake (DRI) recommendations (2, 26, 2.5, and 13%, respectively). Conclusion: According to the poor dietary quality of bariatric surgery candidates, leading to nutritional deficiencies pre-operatively, close monitoring and tailored supplementation pre- and post-bariatric surgery are required.

Keywords: bariatric surgery, food frequency questionnaire, obesity, nutritional status

Procedia PDF Downloads 172

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

Abstract:

Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 114

Authors: Justina I. R. Udotong, Essien U. Essien

Abstract:

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65 mg/l of Pb, 0.85 mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Keywords: diagnostic enzymes, enzyme activity, heavy metals, tissues investigations

Procedia PDF Downloads 290

Authors: Hanen Bouaziz-Ketata, Ghada Ben Salah, Hichem Ben Salah, Kamel Jamoussi, Najiba Zeghal

Abstract:

The present study investigated the protective role of Hyparrhenia hirta on nitrate-induced liver damage. Experiments were carried out on adult rats divided into 3 groups, a control group and two treated groups. NaNO3 was administered daily by oral gavage at a dose of 400 mg/kg bw in treated groups either alone or coadministered with Hyparrhenia hirta methanolic extract via drinking water at a dose of 200 mg/kg bw for 50 days. Liver toxicity induced by NaNO3 was characterized by higher serum levels of glucose, total cholesterol and triglyceride and lower serum total protein than those of controls. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells’ damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, NaNO3 caused oxidant/antioxidant imbalance in the liver as reflected by the increased lipid peroxidation, the decreased total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities. Nitrate caused also a significant induction of DNA fragmentation as evidenced by the presence of a smear without ladder formation on agarose gel. Hyparrhenia hirta supplementation showed an improvement of all parameters cited above. We conclude that the present work provides ethnopharmacological relevance of Hyparrhenia hirta against the toxic effect of nitrate, suggesting its role as a potential antioxidant.

Keywords: Hyparrhenia hirta, liver, nitrate toxicity, oxidative stress, rat

Procedia PDF Downloads 545

Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

Procedia PDF Downloads 266

Authors: Ezomoh O. Olubunmi, Chukwuma S. Anakwe, Bekewei Progress, Prohp The Prophet

Abstract:

Benzene is a volatile organic compound that is recognised as carcinogenic to humans. The objective of the current investigation was to ascertain the impact of the administration of benzene at varying concentrations on the livers of Wistar rats. The 40 adult female Wistar rats were divided into 10 groups, each consisting of four rats. For 28 days, Group 1 received distilled water, while Groups 2 to 10 were administered 0.04,0.06,0.08,0.2,0.4,0.6,0.8,1.0, and 1.2 ml/kg body weight of analytical grade benzene. Blood samples were obtained through cardiac puncture for liver function assessment, while the animals in groups 1 to 5 were euthanised after the 28th day under chloroform anaesthesia. The animals in groups 6 to 10 died midway through the study period. Antioxidant analysis was conducted on liver tissues that were collected and homogenised. The results indicated a substantial (p<0.05), dose-dependent increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities as a result of benzene exposure. Additionally, benzene resulted in a substantial reduction in the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver tissue, as well as an increase in malondialdehyde (MDA) concentrations, and this effect was dose-dependent. These findings emphasise the hepatotoxic effects of benzene, even at concentrations that are relatively low.

Keywords: benzene, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, antioxidants, superoxide dismutase, catalase, glutathione peroxidase

Procedia PDF Downloads 21

Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

Abstract:

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

Procedia PDF Downloads 457

Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

Abstract:

Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

Procedia PDF Downloads 376

Authors: J. Manuel Bello-López, Julieta Rojo-Medina

Abstract:

Introduction: The transplant of Umbilical Cord Blood Units (UCBU) are a therapeutic possibility for patients with oncohaematological disorders, especially in children. In Mexico, 48.5% of oncological diseases in children 1-4 years old are leukemias; whereas in patients 5-14 and 15-24 years old, lymphomas and leukemias represent the second and third cause of death in these groups respectively. Therefore it is necessary to have more registries of UCBU in order to ensure genetic diversity in the country; the above because the search for appropriate a UCBU is increasingly difficult for patients of mixed ethnicity. Objective: To estimate the genetic diversity (polymorphisms) of Human Leucocyte Antigen (HLA) Class I (A, B) and Class II (DRB1) in UCBU cryopreserved for transplant at Cord Blood Bank of the NCBT. Material and Methods: HLA typing of 533 UCBU for transplant was performed from 2003-2012 at the Histocompatibility Laboratory from the Research Department (evaluated by Los Angeles Ca. Immunogenetics Center) of the NCBT. Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity detected by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. A strict analysis of populations genetic parameters were done in 5 representative UCBU populations. Results: 46.5% of UCBU were collected from Mexico City, State of Mexico (30.95%), Puebla (8.06%), Morelos (6.37%) and Veracruz (3.37%). The remaining UCBU (4.75%) are represented by other states. The identified genotypes correspond to Amerindian origins (HLA-A*02, 31; HLA-B*39, 15, 48), Caucasian (HLA-A*02, 68, 01, 30, 31; HLA-B*35, 15, 40, 44, 07 y HLA-DRB1*04, 08, 07, 15, 03, 14), Oriental (HLA-A*02, 30, 01, 31; HLA-B* 35, 39, 15, 40, 44, 07,48 y HLA-DRB1*04, 07,15, 03) and African (HLA-A*30 y HLA-DRB1*03). The genetic distances obtained by Cavalli-Sforza analysis of the five states showed significant genetic differences by comparing genetic frequencies. The shortest genetic distance exists between Mexico City and the state of Puebla (0.0039) and the largest between Veracruz and Morelos (0.0084). In order to identify significant differences between this states, the ANOVA test was performed. This demonstrates that UCBU is significantly different according to their origin (P <0.05). This is shown by the divergence between arms at the Dendogram of Neighbor-Joining. Conclusions: The NCBT provides UCBU in patients with oncohaematological disorders in all the country. There is a group of patients for which not compatible UCBU can be find due to the mixed ethnic origin. For example, the population of northern Mexico is mostly Caucasian. Most of the NCBT donors are of various ethnic origins, predominantly Amerindians and Caucasians; although some ethnic minorities like Oriental, African and pure Indian ethnics are not represented. The NCBT is, therefore, establishing agreements with different states of Mexico to promote the altruistic donation of Umbilical Cord Blood in order to enrich the genetic diversity in its files.

Keywords: cord blood, genetic diversity, human leucocyte antigen, transplant

Procedia PDF Downloads 382

Authors: Ola Abdel-Tawab Hussein

Abstract:

Background: Boron is a naturally occurring agent and an essential trace element of human, animals and higher plants. It is released in the form of boric acid (BA) that is water soluble and biolologically available. Its largest uses are in glass, detergents, agriculture, leather tanning industries, cosmetics, photographic materials, soaps and cleaners. Human consume daily few milligrams in the water, fruits and vegetables. High doses of boron had been recorded to be developmental and reproductive toxin in animals(Only few studies on human had investigated the health effects associated with exposure to boron. Vitamin C is a major water soluble non-enzymatic antioxidant, acts to overcome the oxidative stress. Aim of the work: However , the liver is exposed to toxic substances that are absorbed, degraded or conjugated there were little information exists about the effects of boron that it would specifically have in the liver tissue of experimental rats. So the present work aimed to study the effects of long-term boron ingestion on histological structural of the liver of adult male albino rats and to evaluate the protective role of vitamin C against induced changes. Material and Methods: 30 adult male albino rats were divided into 3 equal groups; Group I: control, Group II: recieved drinking water containing 55x10-6 gm boron/liter for 90 days and Group III: recieved vitamin C (200mg/Kg.B.W) orally concomitant with boron for the same period. liver specimens were processed for light and electron microscopic(TEM) study. Results: Examination of the liver sections of group II revealed foci of severe dilatation and congestion of central and portal veins with mononuclear cellular infiltration and hepatocellular vacuolation. Increased collagen deposition specially around the portal areas. Marked electrolucent areas in the cytoplasm, heterochromatic nuclei and destroyed organelles of the hepatocytes. Apoptotic cells were observed and decreased lipid content of ito cells. In Group III the co administration of vitamin C improved most of the structural changes of the hepatocytes, Ito cells, increased binucleated cells and decreased collagen fibers deposition. Conclusion: Thus, the long term exposure to boron, induced histological changes on the structure of liver. The co administration of vitamin C improved most of these structural changes.

Keywords: boron, liver, vitamin C, rats

Procedia PDF Downloads 346

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

Procedia PDF Downloads 301

Authors: Brahim Bellali, Fatima Bellali

Abstract:

The integration of information technology systems (ITS) into a company's human resources processes seems to be the appropriate solution to the problem of evolving and adapting its human resources management practices in order to be both more strategic and more efficient in terms of costs and service quality. In this context, the aim of this work is to study the impact of information technology systems (ITS) on the recruitment process. In this study, we targeted candidates who had recruited using IT tools. The target population consists of 34 candidates based in Casablanca, Morocco. In order to collect the data, a questionnaire had to be drawn up. The survey is based on a data sheet and a questionnaire that is divided into several sections to make it more structured and comprehensible. The results show that the majority of respondents say that companies are making greater use of online CV libraries and social networks as digital solutions during the recruitment process. The results also show that 50% of candidates say that the use of digital tools by companies would not slow them down when applying for a job and that these IT tools improve manual recruitment processes, while 44.1% think that they facilitate recruitment without any human intervention. The majority of respondents (52.9%) think that social networks are the digital solutions most often used by recruiters in the sourcing phase. The constraints of digital recruitment encountered are the dehumanization of human resources (44.1%) and the limited interaction during remote interviews (44.1%), which leaves no room for informal exchanges. Digital recruitment can be a highly effective strategy for finding qualified candidates in a variety of fields. Here are a few recommendations for optimizing your digital recruitment process: (1) Use online recruitment platforms: LinkedIn, Twitter, and Facebook ; (2) Use applicant tracking systems (ATS) ; (3) Develop a content marketing strategy.

Keywords: IT systems, recruitment, challenges, constraints

Procedia PDF Downloads 33

Authors: Karen Lesley Webster, Charles Crothers

Abstract:

As the population of the Auckland region in New Zealand becomes markedly more super-diverse, the question of fair and effective representation becomes increasingly relevant. This paper explores who stood and who was elected to local office, in the three Auckland triennial local elections, following the 2010 amalgamation of the regions local authorities. It addresses the question of how representative the electoral candidates and elected members of local government in Auckland were of the diverse population they serve. A quantitative analysis of the gender and ethnicity of the Auckland Council candidates and elected members in 2013, 2016, and 2019 triennial elections was undertaken, and the gender and ethnicity compared with that of the Auckland population. Our findings show that under the two-tiered shared governance model established by the Local Government Act (Auckland Council) 2009, electoral candidates have become more ethnically and gender representative of Aucklanders at the local level, while at the regional level, divergence from predominantly New Zealand European, male local representatives is emerging, albeit with less pace. These findings warrant further investigation, but overall, the research presents a cautiously optimistic picture of Auckland local democracy in terms of increasing representational diversity.

Keywords: local government, representation, diversity, gender, ethnicity

Procedia PDF Downloads 332

Authors: Tsegyu Santas

Abstract:

The aim of this study was to examine the utilization of social media for political communication during the 2011 presidential election in Nigeria. The research design adopted for the study was survey; 294 copies of questionnaire were distributed to students of mass communication in three selected universities in North Central Nigeria. Simple random sampling technique was used to select the respondents for the study. The results of the descriptive statistics show that majority of the respondents choice of presidential candidates during the 2011 presidential election was influenced by the use of social media as indicated by high value of mean (1.5805). Similarly, a large number of respondents were of the opinion that the two selected presidential candidates were popular because they used social media in their political campaign (mean value of 1.5575). In addition, the respondents affirmed that their voting pattern during the 2011 presidential elections was influenced by social media usage. This was validated by a high mean value of (1.6667). Similarly, the result of the test of hypothesis indicated that voters’ choice of political candidates was influenced by political communication on social media. In view of the findings of this study, the study, therefore, concludes that social media have redefined the landscape of political communication in Nigeria. Based on the findings of the study, it was recommended that social media should be fully integrated in Nigeria political communication system.

Keywords: communication, election, politics, social media

Procedia PDF Downloads 338

Authors: Evren Şar İşbilen

Abstract:

As it is known, the movies and tv series are occupying a large part in the daily lives of adults and children in our era. In this connection, in the present study, the most popular historical TV series of recent years in Turkey, “Muhteşem Yüzyıl” (The Magnificent Century), was selected as the sample for the data collection in order to explore the perception of history of university students’. The data collected was analyzed bothqualitatively and quantitatively. The findings discussed in relation to the possible educative effects of historical non-educational TV series and movies on students' perceptions related to history. Additionally, suggestions were made regarding to the utilization of non-educational TV series or movies in education in a positive way.

Keywords: education, history, movies, teacher candidates

Procedia PDF Downloads 333

Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

Abstract:

The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

Procedia PDF Downloads 482

Authors: Brahim Bellali, Fatima Bellali

Abstract:

The integration of information technology systems (ITS) into a company's ‘human resources processes seems to be the appropriate solution to the problem of evolving and adapting its human resources management practices in order to be both more strategic and more efficient in terms of costs and service quality. In this context, the aim of this work is to study the impact of information technology systems (ITS) on the recruitment process. In this study, we targeted candidates who had recruited using IT tools. The target population consists of 34 candidates based in Casablanca, Morocco. In order to collect the data, a questionnaire had to be drawn up. The survey is based on a data sheet and a questionnaire that is divided into several sections to make it more structured and comprehensible. The results show that the majority of respondents say that companies are making greater use of online CV libraries and social networks as digital solutions during the recruitment process. The results also show that 50% of candidates say that the use of digital tools by companies would not slow them down when applying for a job and that these IT tools improve manual recruitment processes, while 44.1% think that they facilitate recruitment without any human intervention. The majority of respondents (52.9%) think that social networks are the digital solutions most often used by recruiters in the sourcing phase. The constraints of digital recruitment encountered are the dehumanization of human resources (44.1%) and the limited interaction during remote interviews (44.1%), which leaves no room for informal exchanges. Digital recruitment can be a highly effective strategy for finding qualified candidates in a variety of fields. Here are a few recommendations for optimizing your digital recruitment process: (1) Use online recruitment platforms: LinkedIn, Twitter, and Facebook ; (2) Use applicant tracking systems (ATS) ; (3) Develop a content marketing strategy.

Keywords: IT systems, recruitment, challenges, constraints

Procedia PDF Downloads 9

Authors: Bellali Brahim, Bellali Fatima

Abstract:

The integration of information technology systems (ITS) into a company's ‘human resources processes seems to be the appropriate solution to the problem of evolving and adapting its human resources management practices in order to be both more strategic and more efficient in terms of costs and service quality. In this context, the aim of this work is to study the impact of nformation technology systems (ITS) on the recruitment process. In this study, we targeted candidates who had recruited using IT tools. The target population consists of 34 candidates based in Casablanca, Morocco. In order to collect the data, a questionnaire had to be drawn up. The survey is based on a data sheet and a questionnaire that is divided into several sections to make it more structured and comprehensible. The results show that the majority of respondents say that companies are making greater use of online CV libraries and social networks as digital solutions during the recruitment process. The results also show that 50% of candidates say that the use of digital tools by companies would not slow them down when applying for a job and that these IT tools improve manual recruitment processes, while 44.1% think that they facilitate recruitment without any human intervention. The majority of respondents (52.9%) think that social networks are the digital solutions most often used by recruiters in the sourcing phase. The constraints of digital recruitment encountered are the dehumanization of human resources (44.1%) and the limited interaction during remote interviews (44.1%), which leaves no room for informal exchanges. Digital recruitment can be a highly effective strategy for finding qualified candidates in a variety of fields. Here are a few recommendations for optimizing your digital recruitment process: (1) Use online recruitment platforms: LinkedIn, Twitter, and Facebook ; (2) Use applicant tracking systems (ATS) ; (3) Develop a content marketing strategy.

Keywords: IT systems, recruitment, challenges, constraints

Procedia PDF Downloads 26

Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

Procedia PDF Downloads 309

Authors: Angelis P. Barlampas

Abstract:

PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

Procedia PDF Downloads 96

Authors: I. M. Fakai, A. Abdulhamid, I. Sani, F. Bello, E. O. Olusesi

Abstract:

The phytochemical screening and hepatotoxic effect of Datura metel aqueous seeds extract in Albino Wistar rats were evaluated. Phytochemicals were screened using standard methods. The enzymes activity and liver function indices were also determined using standard methods of analysis. The phytochemicals screening revealed the presence of alkaloid, tannin, glycoside and flavonoid. The organ-body weight decreased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The activity of alkaline phosphatase decreased significantly (P<0.05) in the liver and increased significantly in the serum at all the doses of the extract treated groups compared to the control. The activity of serum alanine transaminase increased significantly (P<0.05) while there is no significant difference (P>0.05) in the activity liver alanine transaminase at all the doses of the extract treated groups compared to the control. The result also revealed significant increase (P<0.05) in the aspartate transaminase activity in both liver and serum at all doses of the extract treated groups compared to the control. Serum total protein, albumin, globulin, and total bilirubin concentration decreased significantly (P<0.05), while direct bilirubin concentration increased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The present study therefore revealed that, the present of some phytochemicals in the plant extract attributed the plant to its hepatotoxic effects as revealed in the alteration of marker enzymes and some liver function indices analyzed.

Keywords: datura metel, transaminases, hepatotoxic effect, phytochemicals, rats

Procedia PDF Downloads 444

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

Abstract:

Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

Procedia PDF Downloads 183