Search results for: hematological malignancies

Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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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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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Hacer Kobya Bulut, Ilknur Kahriman, Birsel C. Demirbag

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Introduction and Purpose: The lives of children with cancer are affected by long term hospitalizations in a negative way due to complications arising from diagnosis or treatment. However, the children's parents are known to have difficulties in meeting their children’s needs and providing home care after cancer treatment or during remission process. Supporting these children and their parents by giving a planned discharge training starting from the hospital and home care leads to reducing hospital applications, hospitalizations, hospital costs, shortening the length of hospital stay and increasing the satisfaction of the children with cancer and their families. This study was conducted to investigate the status of children and their parents' unplanned application to hospital and re-hospitalization. Methods: The study was carried out with 65 children with hematological malignancy in 0-17 age group and their families in a hematology clinic and polyclinic of a university hospital in Trabzon. Data were collected with survey methodology between August-November, 2015 through face to face interview using numbers, percentage and chi-square test in the evaluation. Findings: Most of the children were leukemia (90.8%) and 49.2% had been ill over 13 months. Few of the parents (32.3%) stated that they had received discharge and home care training (24.6%) but most of them (69.2%) found themselves enough in providing home care. Very few parents (6.2%) received home care training after their children being discharged and the majority of parents (61.5%) faced difficulties in home care and had no one to call around them. The parents expressed that in providing care to their children with hematological malignance, they faced difficulty in feeding them (74.6%), explaining their disease (50.0%), giving their oral medication (47.5%), providing hygiene (43.5%) and providing oral care (39.3%). The question ‘What are the emergency situations in which you have to bring your children to a doctor immediately?' was replied as fever (89.2%), severe nausea and vomiting (87.7%), hemorrhage (86.2%) and pain (81.5%). The study showed that 50.8% of the children had unplanned applications to hospitals and 33.8% of them identified as unplanned hospitalization and the first causes of this were fever and pain. The study showed that the frequency of applications (%78.8) and hospitalizations (%81.8) was higher for boys and a statistically significant difference was found between gender and unplanned applications (X=4.779; p=0.02). Applications (48.5%) and hospitalizations (40.9%) were found lower for the parents who had received hospital discharge training, and a significant difference was determined between receiving training and unplanned hospitalizations (X=8.021; p=0.00). Similarly, applications (30.3%) and hospitalizations (40.9%) was found lower for the ones who had received home care training, and a significant difference was determined between receiving home care training and unplanned hospitalizations (X=4.758; p=0.02). Conclusion: It was found out that caregivers of children with cancer did not receive training related to home care and complications about treatment after discharging from hospital, so they faced difficulties in providing home care and this led to an increase in unplanned hospital applications and hospitalizations.

Keywords: cancer, children, unplanned application, unplanned hospitalization

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Z. Razi, S. M. J. Mortazavi, N. Shokrpour, Z. Shayan, F. Amiri

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Long-term exposure to low doses of ionizing radiation occurs in radiation health care workplaces. Although doses in health professions are generally very low, there are still matters of concern. The radiation safety program promotes occupational radiation safety through accurate and reliable monitoring of radiation workers in order to effectively manage radiation protection. To achieve this goal, it has become mandatory to implement health examination periodically. As a result, based on the hematological alterations, working populations with a common occupational radiation history are screened. This paper calls into question the effectiveness of blood component analysis as a screening program which is mandatory for medical radiation workers in some countries. This study details the distribution and trends of changes in blood components, including white blood cells (WBCs), red blood cells (RBCs) and platelets as well as received cumulative doses from occupational radiation exposure. This study was conducted among 199 participants and 100 control subjects at the medical imaging departments at the central hospital of Shiraz University of Medical Sciences during the years 2006–2010. Descriptive and analytical statistics, considering the P-value<0.05 as statistically significance was used for data analysis. The results of this study show that there is no significant difference between the radiation workers and controls regarding WBCs and platelet count during 4 years. Also, we have found no statistically significant difference between the two groups with respect to RBCs. Besides, no statistically significant difference was observed with respect to RBCs with regards to gender, which has been analyzed separately because of the lower reference range for normal RBCs levels in women compared to men and. Moreover, the findings confirm that in a separate evaluation between WBCs count and the personnel’s working experience and their annual exposure dose, results showed no linear correlation between the three variables. Since the hematological findings were within the range of control levels, it can be concluded that the radiation dosage (which was not more than 7.58 mSv in this study) had been too small to stimulate any quantifiable change in medical radiation worker’s blood count. Thus, use of more accurate method for screening program based on the working profile of the radiation workers and their accumulated dose is suggested. In addition, complexity of radiation-induced functions and the influence of various factors on blood count alteration should be taken into account.

Keywords: blood cell count, mandatory testing, occupational exposure, radiation

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Authors: Jully Handoko

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Screening for anaemia in Bali cattle of Bangkinang Seberang subdistrict, kampar regency, Riau, Indonesia, had been conducted. The aim of the study was to analyse hematological alterations in the anaemic Bali cattle. A number of 75 Bali cattle were screened for anaemia on the basis of Haemoglobin (Hb) concentration. The other haematological parameters that were measured including packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). The screening showed that 18 (24.00%) of Bali cattle were anaemic. Haematological values of Hb, PCV, TEC, MCV, MCH, and MCHC were significantly (p<0.05) lower in anaemic Bali cattle compared to non-anaemic Bali cattle.

Keywords: anaemia, Bali cattle, alteration, semi-intensive system

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Authors: Monika Rezacova

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Radiation-induced breast changes are a consequence of radiotherapy toxicity over the breast tissues either related to targeted breast cancer treatment or other thoracic malignancies (eg. lung cancer). This study has created an overview of different changes and their pathophysiology. The main conditions included were skin thickening, interstitial oedema, fat necrosis, dystrophic calcifications, skin retractions, glandular atrophy, breast fibrosis and radiation induced breast cancer. This study has performed focused literature search through multiple databases including pubmed, medline and embase. The study has reviewed English as well as non English publications. As a result of the literature the study provides comprehensive overview of radiation-induced breast changes and their pathophysiology with small focus on new development and prevention.

Keywords: radiotherapy toxicity, breast tissue changes, breast cancer treatment, radiation-induced breast changes

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Authors: G. Vasanthi

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The purpose of the study was to analyse the red blood cells and white blood cells during three different menstrual phases between sedentary and sports women. To achieve this purpose, fifteen female sedentary post graduate students (M.A., M.Sc.) and fifteen students of Master of Physical Education and Sports (M.P.Ed.) women who regularly involved in vigouous sports training and participated in sports competition on different games were selected by adopting random sampling method. All the students were hostelers and their age group was between 20 to 22 years. The blood sample were collected during the mid-period of the three different phases to calculate the red blood cells and white blood cells. The data collected were treated statistically by using analysis of variance. The results reveal that the RBC and WBC is found to be significant between sedentary and sports women during the three different menstrual phases.

Keywords: RBC, WBC, menstrual, proliferative, secretary, sedentary women, sports women

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Authors: Sarah Bouayyad, Ajay Nigam, Meera Beena

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Acquired benign tracheoesophageal fistula is a rare medical condition that usually results from trauma, foreign bodies, or granulomatous infections. This is an unusual presentation of a male patient with a history of laryngectomy who had had over a period of several years inappropriately and vigorously used valve cleaning brushes to clean tracheal secretions, which had led to the formation of a tracheoesophageal fistula. Due to the patient’s obsessive habit, we couldn’t manage him using conventional surgical methods. Instead, we opted for the placement of a salivary bypass tube, which yielded good results and recovery. To the best of our knowledge, no other case of similar etiology has been published. We would like to highlight the importance of appropriate patient selection and education prior to performing a tracheoesophageal puncture to avoid developing life-threatening complications as demonstrated in our case report.

Keywords: tracheoesophageal fistula, speech valve, endoscopic insertion of salivary bypass tube, head and neck malignancies

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a low-grade inflammatory state. Childhood obesity is a multisystem disease, which is associated with a number of complications as well as potentially negative consequences. Gender is an important universal risk factor for many diseases. Hematological indices differ significantly by gender. This should be considered during the evaluation of obese children. The aim of this study is to detect hematologic indices that differ by gender in morbid obese (MO) children. A total of 134 MO children took part in this study. The parents filled an informed consent form and the approval from the Ethics Committee of Namik Kemal University was obtained. Subjects were divided into two groups based on their genders (64 females aged 10.2±3.1 years and 70 males aged 9.8±2.2 years; p ≥ 0.05). Waist-to-hip as well as head-to-neck ratios and body mass index (BMI) values were calculated. The children, whose WHO BMI-for age and sex percentile values were > 99 percentile, were defined as MO. Hematological parameters [haemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, leukocyte count, neutrophil %, lymphocyte %, monocyte %, eosinophil %, basophil %, platelet count, platelet distribution width, mean platelet volume] were determined by the automatic hematology analyzer. SPSS was used for statistical analyses. P ≤ 0.05 was the degree for statistical significance. The groups included children having mean±SD value of BMI as 26.9±3.4 kg/m² for males and 27.7±4.4 kg/m² for females (p ≥ 0.05). There was no significant difference between ages of females and males (p ≥ 0.05). Males had significantly increased waist-to-hip ratios (0.95±0.08 vs 0.91±0.08; p=0.005) and mean corpuscular hemoglobin concentration values (33.6±0.92 vs 33.1±0.83; p=0.001) compared to those of females. Significantly elevated neutrophil (4.69±1.59 vs 4.02±1.42; p=0.011) and neutrophil-to-lymphocyte ratios (1.70±0.71 vs 1.39±0.48; p=0.004) were detected in females. There was no statistically significant difference between groups in terms of C-reactive protein values (p ≥ 0.05). Adipose tissue plays important roles during the development of obesity and associated diseases such as metabolic syndrom and cardiovascular diseases (CVDs). These diseases may cause changes in complete blood cell count parameters. These alterations are even more important during childhood. Significant gender effects on the changes of neutrophils, one of the white blood cell subsets, were observed. The findings of the study demonstrate the importance of considering gender in clinical studies. The males and females may have distinct leukocyte-trafficking profiles in inflammation. Female children had more circulating neutrophils, which may be the indicator of an increased risk of CVDs, than male children within this age range during the late stage of obesity. In recent years, females represent about half of deaths from CVDs; therefore, our findings may be the indicator of the increasing tendency of this risk in females starting from childhood.

Keywords: children, gender, morbid obesity, neutrophil-to-lymphocyte ratio

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Authors: D. Furuya, H. Ryujin, S. Takahira, Y. Sekine, Y. Oya, K. Sonoda, H. Ogawa, Y. Nomura, R. Maruyama, H. Kim, T. Kudo, A. Nakano, T. Saruta, S. Sugita, M. Nemoto, N. Tanahashi

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Purpose: To study the clinical characteristics of hypoglycemic coma in adult patients with type 1 or type 2 diabetes mellitus (DM). Methods: Participants in this retrospective study comprised 91 patients (54 men, 37 women; mean age ± standard deviation, 71.5 ± 12.6 years; range, 42-97 years) brought to our emergency department by ambulance with disturbance of consciousness in the 7 years from April 2007 to March 2014. Patients with hypoglycemia caused by alcoholic ketoacidosis, nutrition disorder, malignancies and psychological disorder were excluded. Results: Patients with type 1 (8 of 91) or type 2 DM (83 of 91) were analyzed. Mean blood sugar level was 31.6 ± 10.4 in all patients. A sulfonylurea (SU) was more commonly used in elderly (>75 years old; n=44)(70.5%) than in younger patients (36.2%, p < 0.05). Cases showing prolonged unconsciousness (range, 1 hour to 21 days; n=30) included many (p < 0.05) patients with dementia (13.3%; 0.5% without dementia) and fewer (p < 0.05) patients with type 1 DM (0%; 13.1% in type 2 DM). Specialists for DM (n=33) used SU less often (24.2%) than general physicians (69.0%, p < 0.05). Conclusion: In cases of hypoglycemic coma, SU was frequently used in elderly patients with DM.

Keywords: hypoglycemic coma, Diabetes mellitus, unconsciousness, elderly patients

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Authors: Alireza Vakili, Shahab Ehtesham, Mohsen Danesh Mesgaran

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The objective of this study was use different levels of spent mushroom substrate as a suitable substitute for wheat straw in the ration of male lambs. In this study 20 male lambs with the age of 90 days and initial average weight of 33± 1.7 kg were used. The animals were divided separately into single boxes with four treatments (control treatment, spent mushroom substrate 15%, spent mushroom substrate 25% and spent mushroom substrate 35%) and five replications. The experiment period was 114 days being 14 days adaptation and 90 days for breeding. On the days 36 and 94, blood samples were taken from the jugular vein. In order to carry out the trial, 20 male lambs received the four experimental diets in completely randomized design. The statistical analyses were carried out by using the GLM procedure of SAS 9.1. Means among treatments were compared by Tukey test. The results of the study showed that there was no significant differences between the serum biochemical and hematological contents of the lambs in the four treatments (p>0.05). It was concluded that spent mushroom substrate consumption has no harmful effect on the blood parameters of Kurdish male lambs.

Keywords: alternative food, nutrition, sheep performance, spent mushroom substrate

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Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

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This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 µg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters and histopathological examination of various rabbits’ organs. Tissue distribution of AuNPs was evaluated at a dose of 300 µg/ kg in male rabbit. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions in lung and liver cells were induced in rabbits treated at the300 µg/ kg dose level. The highest gold levels were found in the spleen, followed by liver, lungs and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: gold nanoparticles, toxicity, pathology, hematology, liver function, kidney function

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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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Authors: Jayanthi Sivaraman

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Claudins are the important components of the tight junctions that play a key role in paracellular permeability. Among various members of Claudin family, Claudin 4 (CLDN4) is found to be overexpressed in ovarian, pancreatic carcinomas and other epithelial malignancies. Therefore, in this study, an attempt has been made to identify potent inhibitors for CLDN4 from the ZINC database using virtual screening, molecular docking and molecular dynamics simulations. A well refined molecular model of CLDN4 was built using Prime of Schrodinger v10.2(Template- PDB ID: 4P79). Approximately, 6 million compounds from ZINC database are subjected to high-throughput virtual screening (HTVS) against the active site of CLDN4. Molecular docking using GLIDE predicted ARG31, ASN142, ASP146 and ARG158 as critically important residues. Furthermore, three compounds from ZINC database (ZINC96331839, ZINC36533519 and ZINC75819394) showed highly promising ADME properties and binding affinity with stable conformation. The therapeutic efficiency of these lead compounds is evaluated and confirmed by in-vitro and in-vivo studies which leads to the development of novel anti-cancer drugs.

Keywords: ADME property, inhibitors, molecular docking, virtual screening

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Authors: Ines Zemni, Maher Slimane, Jamel Ben Hassouna, Khaled Rahal

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Background: Neurofibromatosis type 1 (NF1) is a genetic disease, which is associated with an increased risk of developing different malignancies including breast cancer. The association between NF1 band breast sarcoma is a rare entity. Herein we present a 25-year-old woman with NF1 who had fibrosarcoma of the left breast. Case presentation: The patient has multiple thoraco-abdominal 'café au lait' spots. Clinical examination showed a lump of the left breast measuring 9 cm of diameter, which was noticed for 6 months. There was a left inguinal mass of 6 cm of diameter. The patient underwent first a left lumpectomy. Histopathological exam revealed a high-grade fibrosarcoma of the left breast measuring 7.5 cm. Three months later, the patient underwent a left mastectomy and excision of the inguinal mass, which was a neurofibroma. An adjuvant chemotherapy and radiation therapy were indicated, but not applied because of the timeout. The patient is now alive after a follow up of 6 years, with no loco-regional recurrence or metastasis. Conclusion: The relationship between NF1 and breast cancer need to be more clarified by further studies. Establishing a specific screening program of these patients may help to make an earlier diagnosis of breast cancer.

Keywords: neurofibromatosis, breast, sarcoma, cancer

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Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

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Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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Authors: Vishal Bhatnagar

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The objective of this study is to compare the efficacy of epidural analgesia of two amide local anesthetics, ropivacaine and levobupivacaine, with fentanyl for postoperative analgesia in major abdominal surgery CRS+HIPEC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) are done for primary peritoneal malignancies or peritoneal spread of malignant neoplasm. CRS and HIPEC are considered one of the most painful surgery among all major abdominal surgeries. Poorly managed postoperative pain elevates stress, increases anxiety, causes prolonged Hospital stay, increases opioid requirement and side effects, increases the cost of treatment and psychological effects on patient and family. It affects the quality of life of patients. The epidural technique provides better postoperative analgesia, earlier recovery of bowel function, fewer side effects, higher patient satisfaction, and an improvement in life quality in the postoperative days after abdominal surgery than other analgesic techniques.

Keywords: HIPEC, postoperative analgesia, cytoreductive surgery, VAS score, rescue analgesia

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Authors: N. S. Okoro

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An experiment was conducted to determine the growth performance, blood parameters and reproductive characteristics of 8-week old male weaner rabbits fed 2% boiled pigeon pea seed meal. The study lasted for 16 weeks. Results showed that hematological parameters of the two groups of rabbit bucks were not significantly affected (p > 0.05) by the treatment, meaning that the PPSM was adequate for maintaining the blood parameters at the normal levels. The 20% boiled PPSM significantly affected (P < 0.05) serum Alanine Aminotransferase (ALT) (67.72±2.5 I.U/I) more than the ALT (57.50±2.02 I.U/I) of the control, which is an indication of liver problem. The globulin level (3.00 ± 0.23g/dl) of the 20% boiled PPSM group was significantly higher than that of the control (2.60±0.06 g/dl), indicating that the test diet did not alter protein metabolism in the rabbits. Boiled pigeon pea seed meal supported organ weight and testicular development in rabbit bucks, suggesting that boiling reduced the level of the anti-nutritional factors in pigeon pea seed meal. Thus, 20% boiled pigeon pea can be included in diets of rabbits without adverse effect on blood parameters and internal organs characteristics.

Keywords: hematology, internal organs, Pigeon pea, rabbits, serum biochemistry

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Authors: Muhammad Mustafa Jafar, Syed Ashar Mahfooz, Muhammad Ejaz Saleem, Muhammad Asif Raza, Asghar Abbas, Rao Zahid Abbas, Muhammad Kasib Khan, Hafiz Muhammad Ishaq

Abstract:

The Babesia gradually attained resistance against the synthetic medicines. To overcome the drug resistance, herbal therapy has gained more attention as compared to allopathic therapy. Peganumharmala (harmal) is a plant which has shown effective results against various protozoal diseases. Therefore, the present study was planned to monitor the efficacy of Peganumharmala (aqueous extract) against Babesiosis in cattle. For this purpose, a total of forty (n=40) infected animals were randomly divided into four equal groups (A, B, C, and D). Group A was treated with aqueous extract of Peganum harmala at 7.5 mg/kg, group B at 10 mg/kg and group C at 12.5 mg/kg of body weight. Group D served as a control group (normal). It was observed that there was a stabilization in hematological parameters (white and red blood cells, hemoglobin and Packed cell volume) in infected animals treated with Peganum harmala at different doses. Results of this study hence indicated that Peganum harmala extract at 12.5mg/kg BW is more effective against Babesiosis than lower doses.

Keywords: Babesiosis, cattle, control, Peganum harmala

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Authors: Mhuji Kilonzo

Abstract:

Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

Procedia PDF Downloads 259

Authors: A. B. Amna, M. A. E. Samia, A. K. Hassan

Abstract:

The clinical, pathological, hematological and biological changes in Newzealand rabbits groups given daily oral doses of 0.1,0.25 and 0.5 ml/kg body weight/day of Cpmbopogon proximus oil extract were investigated in an experiment durated for 21 days. Other than the dose co-related mortality rates, the clinical signs were observed daily after dosing to be low appetite and nervous signs including restlessness and increased consciousness. Pulmonary excretion of the oil extract led to bloody spots on the lungs, lymphocyte infiltration, congestion and edema. Renal glumeruli manifested lymphocyte infiltration in addition to shrinkages and easinophilic material in the medulla, if considered with the corticomedullary generalized necrosis and the significant changes in urea, they can explain the renal dysfunction. Hepatic malfunction was manifested by significant changes in serum alkaline phosphatase and aspartate transferases accompanied by the congested, fatty changed livers. The direct physical effect of the extracted oil was detected by the catarrhal inflammation of the intestines.There was no significant haematological change except for the slight changes in RBCs and MCVs in rabbits given the highest dose. Future work for Cpmbopogon proximus oil extract was forwarded and practical implications of the result were highlighted.

Keywords: toxicity, cymbopogon proximus (maharaib), oil extract, Newzealand rabbits

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Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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Authors: Onur Karaman, A. Gunes Tanir

Abstract:

Photon radiation therapy used to treat cancer is one of the most important methods. However, photon beam collimator materials in Linear Accelerator (LINAC) head generally contains heavy elements is used and the interaction of bremsstrahlung photon with such heavy nuclei, the neutron can be produced inside the treatment rooms. In radiation therapy, neutron contamination contributes to the risk of secondary malignancies in patients, also physicians working in this field. Since the neutron is more dangerous than photon, it is important to determine neutron dose during radiotherapy treatment. In this study, it is aimed to analyze the effect of field size, distance from axis and depth on the amount of in-field and out-field neutron contamination for ElektaVmat accelerator with 18 MV nominal energy. The photon spectra at the distance of 75, 150, 225, 300 cm from target and on the isocenter of beam were scored for 5x5, 10x10, 20x20, 30x30 and 40x40 cm2 fields. Results demonstrated that the neutron spectra and dose are dependent on field size and distances. Beyond 225 cm of isocenter, the dependence of the neutron dose on field size is minimal. As a result, it is concluded that as the open field increases, neutron dose determined decreases. It is important to remember that when treating with high energy photons, the dose from contamination neutrons must be considered as it is much greater than the photon dose.

Keywords: radiotherapy, neutron contamination, linear accelerators, photon

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Authors: Mehdi Tavana, Seyedeh Zeinab Peighambarzadeh

Abstract:

Pyelography is used for morphologic and especially functional studies of the urinary tracts. There are many indications for excretory Pyelography in humans and animals. Intravenous Pyelography is the most practical method; other Pyelography techniques were manipulated because of difficulties for finding veins in small size of the patients. At the best of times, the combination of small veins and abundant subcutaneous tissue makes vascular access difficult or impossible, therefore, another methods of administration of contrast media is desired. This study was performed to evaluate the feasibility of intraosseous injection of iodixanol in providing a safe and diagnostic urogram in Persian squirrel. Fourteen hundred mg iodine per kilogram body weight of iodixanol was injected subcutaneously over tibial tuberosity on ten clinically healthy adult Persian squirrels with no signs of urinary system disorder. Lateral and ventrodorsal radiographs were taken every 2 minutes until the pyelogram was finished. Intraosseous injection of iodixanol was successful to show nephrogram, pyelogram, uretrogram and cystogram clearly. There were no abnormal clinical signs after one week of experiments. Biochemical and hematological profiles were in normal ranges. It is concluded that intraosseous Pyelography is an effective and reliable method for Pyelography studies in squirrel. Microscopic examinations of the kidneys and the site of injection after one week were normal.

Keywords: pyelography, intraosseous injection, iodixanol, persian squirrel

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Authors: Aiche Mohamed Amine, Mallem Leila, Yahia El Khansa, Boulakoud Mohamed Salah

Abstract:

Until recently, toxicological studies focused on the effects of individual chemicals. However, humans and wildlife are exposed to a complex milieu of chemicals from different sources including food and water, personal care products and the environment. The aim of this study is to detect the toxicity of two fungicides and their mixtures in the fertility and oxidative damge induced in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with Propiconazole 60mg/Kg/day, Propinebe 100mg/Kg/day and their mixture 30mg Propiconazole/kg/day + 50mg Propineb/kg/day for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified, blood was collected for hematological and biochemical’s analysis and desired organs were removed and weighted. The results indicated that the fungicide and their mixture were toxic in the treated animals. The semen study showed a decrease in the count and mobility of spermatozoa in all treated group, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Reduced glutathione (GSH), Glutathione peroxidase (GPx) level was decreased in all treated groups.

Keywords: fungicides, mixtures, fertility, oxidative stress

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Authors: Roshika Tyagi, Shuvomoy Banerjee

Abstract:

Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

Procedia PDF Downloads 196

Authors: Mehdi Tavana, Seyedeh Zeinab Peighambarzadeh

Abstract:

Excretory urography is used for morphologic and especially functional studies of the urinary tracts. There are many indications for excretory urography in humans and animals. Intravenous urography is the most practical method, other urography techniques were manipulated because of difficulties for finding veins in small size of the patients. At the best of times, the combination of small veins and abundant subcutaneous tissue make vascular access difficult or impossible, therefore, another methods of administration of contrast media is desired. This study was performed to evaluate the feasibility of intraosseous injection of iodixanol in providing a safe and diagnostic urogram in Persian squirrel. Fourteen hundreds mg iodine per kilogram body weight of iodixanol were injected subcutaneously over tibial tuberosity on ten clinically healthy adult Persian squirrels with no signs of urinary system disorder. Lateral and ventrodorsal radiographs were taken every 2 minutes until the pyelogram was finished. Intraosseous injection of iodixanol was successful to show nephrogram, pyelogram, uretrogram and cystogram clearly. There were no abnormal clinical signs after one week of experiments. Biochemical and hematological profiles were in normal ranges. It is concluded that intraosseous urography is an effective and reliable method for urography studies in squirrel. Microscopic examinations of the kidneys and the site of injection after one week were normal.

Keywords: intraosseous urography, iodixanol, Persian squirrel, morphologic

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Authors: Shweta Maheshwari, Anish Dua

Abstract:

Hematological changes reflect the adverse effects of heavy metals on fish. Hematology is a valuable tool to evaluate pathological condition of the fish. It helps in diagnosing the structural and functional status of fish exposed to toxicants. Morphological alteration in erythrocytes due to environmental stress can be studied through ultra-structural analysis. The aim of the present study was to assess the toxicity of mercuric chloride on red blood cells of an air breathing fish, Channa punctatus. Fish were subjected to chronic experiments using three sublethal concentration of mercuric chloride (0.020mg/L, 0.027mg/L, 0.040mg/L) for a period of 15, 30 and 60 days. Exposed fish of all the three concentrations were subjected to a recovery period of 30 days. A control was maintained in tap water simultaneously. For SEM analysis, blood from caudal vein of fish was taken and examined at an accelerating voltage of 20kV. Scanning electron micrographs revealed elliptical shaped erythrocytes of control fish. Alterations in the erythrocyte morphology such as presence of spherocytes, membrane internalization, crenation of membrane and development of lobopodial projections were observed in the exposed fish. The study revealed that ultra-structural analysis appears to be a sensitive method to evaluate the toxicity of various toxicants to fish.

Keywords: Channa punctatus, erythrocytes, mercuric chloride, scanning electron microscopy

Procedia PDF Downloads 331