Search results for: zero injection buses (ZIB)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1022

Search results for: zero injection buses (ZIB)

62 Comparative Analysis of Costs and Well Drilling Techniques for Water, Geothermal Energy, Oil and Gas Production

Authors: Thales Maluf, Nazem Nascimento

Abstract:

The development of society relies heavily on the total amount of energy obtained and its consumption. Over the years, there has been an advancement on energy attainment, which is directly related to some natural resources and developing systems. Some of these resources should be highlighted for its remarkable presence in world´s energy grid, such as water, petroleum, and gas, while others deserve attention for representing an alternative to diversify the energy grid, like geothermal sources. Therefore, because all these resources can be extracted from the underground, drilling wells is a mandatory activity in terms of exploration, and it involves a previous geological study and an adequate preparation. It also involves a cleaning process and an extraction process that can be executed by different procedures. For that reason, this research aims the enhancement of exploration processes through a comparative analysis of drilling costs and techniques used to produce them. The analysis itself is based on a bibliographical review based on books, scientific papers, schoolwork and mainly explore drilling methods and technologies, equipment used, well measurements, extraction methods, and production costs. Besides techniques and costs regarding the drilling processes, some properties and general characteristics of these sources are also compared. Preliminary studies show that there are some major differences regarding the exploration processes, mostly because these resources are naturally distinct. Water wells, for instance, have hundreds of meters of length because water is stored close to the surface, while oil, gas, and geothermal production wells can reach thousands of meters, which make them more expensive to be drilled. The drilling methods present some general similarities especially regarding the main mechanism of perforation, but since water is a resource stored closer to the surface than the other ones, there is a wider variety of methods. Water wells can be drilled by rotary mechanisms, percussion mechanisms, rotary-percussion mechanisms, and some other simpler methods. Oil and gas production wells, on the other hand, require rotary or rotary-percussion drilling with a proper structure called drill rig and resistant materials for the drill bits and the other components, mostly because they´re stored in sedimentary basins that can be located thousands of meters under the ground. Geothermal production wells also require rotary or rotary-percussion drilling and require the existence of an injection well and an extraction well. The exploration efficiency also depends on the permeability of the soil, and that is why it has been developed the Enhanced Geothermal Systems (EGS). Throughout this review study, it can be verified that the analysis of the extraction processes of energy resources is essential since these resources are responsible for society development. Furthermore, the comparative analysis of costs and well drilling techniques for water, geothermal energy, oil, and gas production, which is the main goal of this research, can enable the growth of energy generation field through the emergence of ideas that improve the efficiency of energy generation processes.

Keywords: drilling, water, oil, Gas, geothermal energy

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61 Study on Co-Relation of Prostate Specific Antigen with Metastatic Bone Disease in Prostate Cancer on Skeletal Scintigraphy

Authors: Muhammad Waleed Asfandyar, Akhtar Ahmed, Syed Adib-ul-Hasan Rizvi

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Objective: To evaluate the ability of serum concentration of prostate specific antigen between two cutting points considering it as a predictor of skeletal metastasis on bone scintigraphy in men with prostate cancer. Settings: This study was carried out in department of Nuclear Medicine at Sindh Institute of Urology and Transplantation (SIUT) Karachi, Pakistan. Materials and Method: From August 2013 to November 2013, forty two (42) consecutive patients with prostate cancer who underwent technetium-99m methylene diphosphonate (Tc-99mMDP) whole body bone scintigraphy were prospectively analyzed. The information was collected from the scintigraphic database at a Nuclear medicine department Sindh institute of urology and transplantation Karachi Pakistan. Patients who did not have a serum PSA concentration available within 1 month before or after the time of performing the Tc-99m MDP whole body bone scintigraphy were excluded from this study. A whole body bone scintigraphy scan (from the toes to top of the head) was performed using a whole-body Moving gamma camera technique (anterior and posterior) 2–4 hours after intravenous injection of 20 mCi of Tc-99m MDP. In addition, all patients necessarily have a pathological report available. Bony metastases were determined from the bone scan studies and no further correlation with histopathology or other imaging modalities were performed. To preserve patient confidentiality, direct patient identifiers were not collected. In all the patients, Prostate specific antigen values and skeletal scintigraphy were evaluated. Results: The mean age, mean PSA, and incidence of bone metastasis on bone scintigraphy were 68.35 years, 370.51 ng/mL and 19/42 (45.23%) respectively. According to PSA levels, patients were divided into 5 groups < 10ng/mL (10/42), 10-20 ng/mL (5/42), 20-50 ng/mL (2/42), 50-100 (3/42), 100- 500ng/mL (3/42) and more than 500ng/mL (0/42) presenting negative bone scan. The incidence of positive bone scan (%) for bone metastasis for each group were O1 patient (5.26%), 0%, 03 patients (15.78%), 01 patient (5.26%), 04 patients (21.05%), and 10 patients (52.63%) respectively. From the 42 patients 19 (45.23%) presented positive scintigraphic examination for the presence of bone metastasis. 1 patient presented bone metastasis on bone scintigraphy having PSA level less than 10ng/mL, and in only 1 patient (5.26%) with bone metastasis PSA concentration was less than 20 ng/mL. therefore, when the cutting point adopted for PSA serum concentration was 10ng/mL, a negative predictive value for bone metastasis was 95% with sensitivity rates 94.74% and the positive predictive value and specificities of the method were 56.53% and 43.48% respectively. When the cutting point of PSA serum concentration was 20ng/mL the observed results for Positive predictive value and specificity were (78.27% and 65.22% respectively) whereas negative predictive value and sensitivity stood (100% and 95%) respectively. Conclusion: Results of our study allow us to conclude that serum PSA concentration of higher than 20ng/mL was the most accurate cutting point than a serum concentration of PSA higher than 10ng/mL to predict metastasis in radionuclide bone scintigraphy. In this way, unnecessary cost can be avoided, since a considerable part of prostate adenocarcinomas present low serum PSA levels less than 20 ng/mL and for these cases radionuclide bone scintigraphy could be unnecessary.

Keywords: bone scan, cut off value, prostate specific antigen value, scintigraphy

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60 Getting to Know ICU Nurses and Their Duties

Authors: Masih Nikgou

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ICU nurses or intensive care nurses are highly specialized and trained healthcare personnel. These nurses provide nursing care for patients with life-threatening illnesses or conditions. They provide the experience, knowledge and specialized skills that patients need to survive and recover. Intensive care nurses (ICU) are trained to make momentary decisions and act quickly when the patient's condition changes. Their primary work environment is in the hospital in intensive care units. Typically, ICU patients require a high level of care. ICU nurses work in challenging and complex fields in their nursing profession. They have the primary duty of caring for and saving patients who are fighting for their lives. Intensive care (ICU) nurses are highly trained to provide exceptional care to patients who depend on 24/7 nursing care. A patient in the ICU is often equipped with a ventilator, intubated and connected to several life support machines and medical equipment. Intensive Care Nurses (ICU) have full expertise in considering all aspects of bringing back their patients. Some of the specific responsibilities of ICU nurses include (a) Assessing and monitoring the patient's progress and identifying any sudden changes in the patient's medical condition. (b) Administration of drugs intravenously by injection or through gastric tubes. (c) Provide regular updates on patient progress to physicians, patients, and their families. (d) According to the clinical condition of the patient, perform the approved diagnostic or treatment methods. (e) In case of a health emergency, informing the relevant doctors. (f) To determine the need for emergency interventions, evaluate laboratory data and vital signs of patients. (g) Caring for patient needs during recovery in the ICU. (h) ICU nurses often provide emotional support to patients and their families. (i) Regulating and monitoring medical equipment and devices such as medical ventilators, oxygen delivery devices, transducers, and pressure lines. (j) Assessment of pain level and sedation needs of patients. (k) Maintaining patient reports and records. As the name suggests, critical care nurses work primarily in ICU health care units. ICUs are completely healthy and have proper lighting with strict adherence to health and safety from medical centers. ICU nurses usually move between the intensive care unit, the emergency department, the operating room, and other special departments of the hospital. ICU nurses usually follow a standard shift schedule that includes morning, afternoon, and night schedules. There are also other relocation programs depending on the hospital and region. Nurses who are passionate about data and managing a patient's condition and outcomes typically do well as ICU nurses. An inquisitive mind and attention to processes are equally important. ICU nurses are completely compassionate and are not afraid to advocate for their patients and family members. who are distressed.

Keywords: nursing, intensive care unit, pediatric intensive care unit, mobile intensive care unit, surgical intensive care unite

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59 Targeted Delivery of Docetaxel Drug Using Cetuximab Conjugated Vitamin E TPGS Micelles Increases the Anti-Tumor Efficacy and Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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58 Study of the Kinetics of Formation of Carboxylic Acids Using Ion Chromatography during Oxidation Induced by Rancimat of the Oleic Acid, Linoleic Acid, Linolenic Acid, and Biodiesel

Authors: Patrícia T. Souza, Marina Ansolin, Eduardo A. C. Batista, Antonio J. A. Meirelles, Matthieu Tubino

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Lipid oxidation is a major cause of the deterioration of the quality of the biodiesel, because the waste generated damages the engines. Among the main undesirable effects are the increase of viscosity and acidity, leading to the formation of insoluble gums and sediments which cause the blockage of fuel filters. The auto-oxidation is defined as the spontaneous reaction of atmospheric oxygen with lipids. Unsaturated fatty acids are usually the components affected by such reactions. They are present as free fatty acids, fatty esters and glycerides. To determine the oxidative stability of biodiesels, through the induction period, IP, the Rancimat method is used, which allows continuous monitoring of the induced oxidation process of the samples. During the oxidation of the lipids, volatile organic acids are produced as byproducts, in addition, other byproducts, including alcohols and carbonyl compounds, may be further oxidized to carboxylic acids. By the methodology developed in this work using ion chromatography, IC, analyzing the water contained in the conductimetric vessel, were quantified organic anions of carboxylic acids in samples subjected to oxidation induced by Rancimat. The optimized chromatographic conditions were: eluent water:acetone (80:20 v/v) with 0.5 mM sulfuric acid; flow rate 0.4 mL min-1; injection volume 20 µL; eluent suppressor 20 mM LiCl; analytical curve from 1 to 400 ppm. The samples studied were methyl biodiesel from soybean oil and unsaturated fatty acids standards: oleic, linoleic and linolenic. The induced oxidation kinetics curves were constructed by analyzing the water contained in the conductimetric vessels which were removed, each one, from the Rancimat apparatus at prefixed intervals of time. About 3 g of sample were used under the conditions of 110 °C and air flow rate of 10 L h-1. The water of each conductimetric Rancimat measuring vessel, where the volatile compounds were collected, was filtered through a 0.45 µm filter and analyzed by IC. Through the kinetic data of the formation of the organic anions of carboxylic acids, the formation rates of the same were calculated. The observed order of the rates of formation of the anions was: formate >>> acetate > hexanoate > valerate for the oleic acid; formate > hexanoate > acetate > valerate for the linoleic acid; formate >>> valerate > acetate > propionate > butyrate for the linolenic acid. It is possible to suppose that propionate and butyrate are obtained mainly from linolenic acid and that hexanoate is originated from oleic and linoleic acid. For the methyl biodiesel the order of formation of anions was: formate >>> acetate > valerate > hexanoate > propionate. According to the total rate of formation these anions produced during the induced degradation of the fatty acids can be assigned the order of reactivity: linolenic acid > linoleic acid >>> oleic acid.

Keywords: anions of carboxylic acids, biodiesel, ion chromatography, oxidation

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57 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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56 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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55 Chinese Acupuncture: A Potential Treatment for Autism Rat Model via Improving Synaptic Function

Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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54 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine

Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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53 A Galectin from Rock Bream Oplegnathus fasciatus: Molecular Characterization and Immunological Properties

Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

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In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

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52 Pentosan Polysulfate Sodium: A Potential Treatment to Improve Bone and Joint Manifestations of Mucopolysaccharidosis I

Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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51 Human Immuno-Deficiency Virus Co-Infection with Hepatitis B Virus and Baseline Cd4+ T Cell Count among Patients Attending a Tertiary Care Hospital, Nepal

Authors: Soma Kanta Baral

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Background: Since 1981, when the first AIDS case was reported, worldwide, more than 34 million people have been infected with HIV. Almost 95 percent of the people infected with HIV live in developing countries. As HBV & HIV share similar routes of transmission by sexual intercourse or drug use by parenteral injection, co-infection is common. Because of the limited access to healthcare & HIV treatment in developing countries, HIV-infected individuals are present late for care. Enumeration of CD4+ T cell count at the time of diagnosis has been useful to initiate the therapy in HIV infected individuals. The baseline CD4+ T cell count shows high immunological variability among patients. Methods: This prospective study was done in the serology section of the Department of Microbiology over a period of one year from august 2012 to July 2013. A total of 13037 individuals subjected for HIV test were included in the study comprising of 4982 males & 8055 females. Blood sample was collected by vein puncture aseptically with standard operational procedure in clean & dry test-tube. All blood samples were screened for HIV as described by WHO algorithm by Immuno-chromatography rapid kits. Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. After informed consent, HIV positive individuals were screened for HBsAg by Immuno-chromatography rapid kits (Hepacard). Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. EDTA blood samples were collected from the HIV sero-positive individuals for baseline CD4+ T count. Then, CD4+ T cells count was determined by using FACS Calibur Flow Cytometer (BD). Results: Among 13037 individuals screened for HIV, 104 (0.8%) were found to be infected comprising of 69(66.34%) males & 35 (33.65%) females. The study showed that the high infection was noted in housewives (28.7%), active age group (30.76%), rural area (56.7%) & in heterosexual route (80.9%) of transmission. Out of total HIV infected individuals, distribution of HBV co-infection was found to be 6(5.7%). All co- infected individuals were married, male, above the age of 25 years & heterosexual route of transmission. Baseline CD4+ T cell count of HIV infected patient was found higher (mean CD4+ T cell count; 283cells/cu.mm) than HBV co-infected patients (mean CD4+ T cell count; 91 cells/cu.mm). Majority (77.2%) of HIV infected & all co-infected individuals were presented in our center late (CD4+ T cell count;< 350/cu. mm) for diagnosis and care. Majority of co- infected 4 (80%) were late presented with advanced AIDS stage (CD4+ count; <200/cu.mm). Conclusions: The study showed a high percentage of HIV sero-positive & co- infected individuals. Baseline CD4+ T cell count of majority of HIV infected individuals was found to be low. Hence, more sustained and vigorous awareness campaigns & counseling still need to be done in order to promote early diagnosis and management.

Keywords: HIV/AIDS, HBsAg, co-infection, CD4+

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50 Optimization of Rehabilitation in Scapolohumeral Periarthrosis Using Botulinum Toxin

Authors: M. A. Akulov, V. O. Zaharov, A. A. Tomskij

Abstract:

Introduction: Scapulohumeral periarthrosis, resulting as a reaction to mechanical injury of shoulder tendons and muscles, is associated with high incidence of temporal and permanent disability. There is a strong need for investigation of treatment of that patient group. Severe pain leads to limitation of movements range, which result in secondary alterations of joint capsule and ligamentous apparatus. Muscle tension and edema, swelling of fascial and fibrous structures result in nerve and vascular compression in intramuscular and osseo-muscular-fibrous spaces. Botulinum toxin injection leads to decrease of muscle tone, increase of movements range and associated pain alleviation. Study aim: Optimization of rehabilitation process in scapolohumeral periarthrosis using Xeomin. Patients and methods: 40 patients aged 37-56 years with scapulohumeral periarthrosis were evaluated. Patients were divided into two groups according to treatment regimen. The first (main) group included 21 patients, receiving intramuscular Xeomin 150-200 U in the area of brachio-scapular joint and trigger points (inducing motion range limitation and pain). Treatment procedures were combined with physical therapy and osteopathic procedures. The second (control) group included 19 patients, receiving conventional physical therapy and osteopathic procedures. The evaluation and efficacy comparison was carried out using McGill pain questionnaire, Clinical Global Impression scale (CGI), and patient-reported increase of brachio-scapular joint movement range and pain decrease at 1, 3 and 6 months of treatment. Results. The study demonstrated a significant improvement in the main group after one month of treatment, which persisted during months of treatment. At baseline, rank pain index on McGill pain questionnaire was 18,4±4,9 and 17,8±5,1 in the main and control group, respectively (p > 0,05). At 1 month of treatment we observed a significant decrease of pain syndrome (no pain or modest pain) and increase of movement range in angular degrees in the main group (р < 0,05). In the control group significant improvements were observed only on the 3 month of treatment (р < 0,05), but at 6 months of treatment the improvement in pain syndrome and motion range in brachio-scapular joint was significantly smaller, than in the main group. Rank pain index on McGill pain scale was 5,2±1,8 in the main group compared to 12,0±2,6 in the control group (р < 0,05). At 6 months of treatment patients in the first group reported a significant/highly significant improvement of general health on CGI, whereas in the second group most patients reported a minimal improvement. We observed a sustained and persistent improvement of motion range in brachio-scapular joint in the main group. Conclusion: Xeomin injections as a part of rehabilitation process in scapulohumeral periarthrosis lead to reduced time and increased quality of rehabilitation.

Keywords: botulinum toxin, rehabilitation, scapulohumeral periarthrosis

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49 Treatment of Onshore Petroleum Drill Cuttings via Soil Washing Process: Characterization and Optimal Conditions

Authors: T. Poyai, P. Painmanakul, N. Chawaloesphonsiya, P. Dhanasin, C. Getwech, P. Wattana

Abstract:

Drilling is a key activity in oil and gas exploration and production. Drilling always requires the use of drilling mud for lubricating the drill bit and controlling the subsurface pressure. As drilling proceeds, a considerable amount of cuttings or rock fragments is generated. In general, water or Water Based Mud (WBM) serves as drilling fluid for the top hole section. The cuttings generated from this section is non-hazardous and normally applied as fill materials. On the other hand, drilling the bottom hole to reservoir section uses Synthetic Based Mud (SBM) of which synthetic oils are composed. The bottom-hole cuttings, SBM cuttings, is regarded as a hazardous waste, in accordance with the government regulations, due to the presence of hydrocarbons. Currently, the SBM cuttings are disposed of as an alternative fuel and raw material in cement kiln. Instead of burning, this work aims to propose an alternative for drill cuttings management under two ultimate goals: (1) reduction of hazardous waste volume; and (2) making use of the cleaned cuttings. Soil washing was selected as the major treatment process. The physiochemical properties of drill cuttings were analyzed, such as size fraction, pH, moisture content, and hydrocarbons. The particle size of cuttings was analyzed via light scattering method. Oil present in cuttings was quantified in terms of total petroleum hydrocarbon (TPH) through gas chromatography equipped with flame ionization detector (GC-FID). Other components were measured by the standard methods for soil analysis. Effects of different washing agents, liquid-to-solid (L/S) ratio, washing time, mixing speed, rinse-to-solid (R/S) ratio, and rinsing time were also evaluated. It was found that drill cuttings held the electrical conductivity of 3.84 dS/m, pH of 9.1, and moisture content of 7.5%. The TPH in cuttings existed in the diesel range with the concentration ranging from 20,000 to 30,000 mg/kg dry cuttings. A majority of cuttings particles held a mean diameter of 50 µm, which represented silt fraction. The results also suggested that a green solvent was considered most promising for cuttings treatment regarding occupational health, safety, and environmental benefits. The optimal washing conditions were obtained at L/S of 5, washing time of 15 min, mixing speed of 60 rpm, R/S of 10, and rinsing time of 1 min. After washing process, three fractions including clean cuttings, spent solvent, and wastewater were considered and provided with recommendations. The residual TPH less than 5,000 mg/kg was detected in clean cuttings. The treated cuttings can be then used for various purposes. The spent solvent held the calorific value of higher than 3,000 cal/g, which can be used as an alternative fuel. Otherwise, the recovery of the used solvent can be conducted using distillation or chromatography techniques. Finally, the generated wastewater can be combined with the produced water and simultaneously managed by re-injection into the reservoir.

Keywords: drill cuttings, green solvent, soil washing, total petroleum hydrocarbon (TPH)

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48 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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47 Numerical Investigation of Combustion Chamber Geometry on Combustion Performance and Pollutant Emissions in an Ammonia-Diesel Common Rail Dual-Fuel Engine

Authors: Youcef Sehili, Khaled Loubar, Lyes Tarabet, Mahfoudh Cerdoun, Clement Lacroix

Abstract:

As emissions regulations grow more stringent and traditional fuel sources become increasingly scarce, incorporating carbon-free fuels in the transportation sector emerges as a key strategy for mitigating the impact of greenhouse gas emissions. While the utilization of hydrogen (H2) presents significant technological challenges, as evident in the engine limitation known as knocking, ammonia (NH3) provides a viable alternative that overcomes this obstacle and offers convenient transportation, storage, and distribution. Moreover, the implementation of a dual-fuel engine using ammonia as the primary gas is promising, delivering both ecological and economic benefits. However, when employing this combustion mode, the substitution of ammonia at high rates adversely affects combustion performance and leads to elevated emissions of unburnt NH3, especially under high loads, which requires special treatment of this mode of combustion. This study aims to simulate combustion in a common rail direct injection (CRDI) dual-fuel engine, considering the fundamental geometry of the combustion chamber as well as fifteen (15) alternative proposed geometries to determine the configuration that exhibits superior engine performance during high-load conditions. The research presented here focuses on improving the understanding of the equations and mechanisms involved in the combustion of finely atomized jets of liquid fuel and on mastering the CONVERGETM code, which facilitates the simulation of this combustion process. By analyzing the effect of piston bowl shape on the performance and emissions of a diesel engine operating in dual fuel mode, this work combines knowledge of combustion phenomena with proficiency in the calculation code. To select the optimal geometry, an evaluation of the Swirl, Tumble, and Squish flow patterns was conducted for the fifteen (15) studied geometries. Variations in-cylinder pressure, heat release rate, turbulence kinetic energy, turbulence dissipation rate, and emission rates were observed, while thermal efficiency and specific fuel consumption were estimated as functions of crankshaft angle. To maximize thermal efficiency, a synergistic approach involving the enrichment of intake air with oxygen (O2) and the enrichment of primary fuel with hydrogen (H2) was implemented. Based on the results obtained, it is worth noting that the proposed geometry (T8_b8_d0.6/SW_8.0) outperformed the others in terms of flow quality, reduction of pollutants emitted with a reduction of more than 90% in unburnt NH3, and an impressive improvement in engine efficiency of more than 11%.

Keywords: ammonia, hydrogen, combustion, dual-fuel engine, emissions

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46 Evaluation of the Boiling Liquid Expanding Vapor Explosion Thermal Effects in Hassi R'Mel Gas Processing Plant Using Fire Dynamics Simulator

Authors: Brady Manescau, Ilyas Sellami, Khaled Chetehouna, Charles De Izarra, Rachid Nait-Said, Fati Zidani

Abstract:

During a fire in an oil and gas refinery, several thermal accidents can occur and cause serious damage to people and environment. Among these accidents, the BLEVE (Boiling Liquid Expanding Vapor Explosion) is most observed and remains a major concern for risk decision-makers. It corresponds to a violent vaporization of explosive nature following the rupture of a vessel containing a liquid at a temperature significantly higher than its normal boiling point at atmospheric pressure. Their effects on the environment generally appear in three ways: blast overpressure, radiation from the fireball if the liquid involved is flammable and fragment hazards. In order to estimate the potential damage that would be caused by such an explosion, risk decision-makers often use quantitative risk analysis (QRA). This analysis is a rigorous and advanced approach that requires a reliable data in order to obtain a good estimate and control of risks. However, in most cases, the data used in QRA are obtained from the empirical correlations. These empirical correlations generally overestimate BLEVE effects because they are based on simplifications and do not take into account real parameters like the geometry effect. Considering that these risk analyses are based on an assessment of BLEVE effects on human life and plant equipment, more precise and reliable data should be provided. From this point of view, the CFD modeling of BLEVE effects appears as a solution to the empirical law limitations. In this context, the main objective is to develop a numerical tool in order to predict BLEVE thermal effects using the CFD code FDS version 6. Simulations are carried out with a mesh size of 1 m. The fireball source is modeled as a vertical release of hot fuel in a short time. The modeling of fireball dynamics is based on a single step combustion using an EDC model coupled with the default LES turbulence model. Fireball characteristics (diameter, height, heat flux and lifetime) issued from the large scale BAM experiment are used to demonstrate the ability of FDS to simulate the various steps of the BLEVE phenomenon from ignition up to total burnout. The influence of release parameters such as the injection rate and the radiative fraction on the fireball heat flux is also presented. Predictions are very encouraging and show good agreement in comparison with BAM experiment data. In addition, a numerical study is carried out on an operational propane accumulator in an Algerian gas processing plant of SONATRACH company located in the Hassi R’Mel Gas Field (the largest gas field in Algeria).

Keywords: BLEVE effects, CFD, FDS, fireball, LES, QRA

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45 Aberrant Acetylation/Methylation of Homeobox (HOX) Family Genes in Cumulus Cells of Infertile Women with Polycystic Ovary Syndrome (PCOS)

Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

Abstract:

Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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44 Monitoring the Effect of Doxorubicin Liposomal in VX2 Tumor Using Magnetic Resonance Imaging

Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

Abstract:

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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43 Role of ASHA in Utilizing Maternal Health Care Services India, Evidences from National Rural Health Mission (NRHM)

Authors: Dolly Kumari, H. Lhungdim

Abstract:

Maternal health is one of the crucial health indicators for any country. 5th goal of Millennium Development Goals is also emphasising on improvement of maternal health. Soon after Independence government of India realizing the importance of maternal and child health care services, and took steps to strengthen in 1st and 2nd five year plans. In past decade the other health indicator which is life expectancy at birth has been observed remarkable improvement. But still maternal mortality is high in India and in some states it is observe much higher than national average. Government of India pour lots of fund and initiate National Rural Health Mission (NRHM) in 2005 to improve maternal health in country by providing affordable and accessible health care services. Accredited Social Heath Activist (ASHA) is one of the key components of the NRHM. Mainly ASHAs are selected female aged 25-45 years from village itself and accountable for the monitoring of maternal health care for the same village. ASHA are trained to works as an interface between the community and public health system. This study tries to assess the role of ASHA in utilizing maternal health care services and to see the level of awareness about benefits given under JSY scheme and utilization of those benefits by eligible women. For the study concurrent evaluation data from National Rural health Mission (NRHM), initiated by government of India in 2005 has been used. This study is based on 78205 currently married women from 70 different districts of India. Descriptive statistics, chi2 test and binary logistic regression have been used for analysis. The probability of institutional delivery increases by 2.03 times (p<0.001) while if ASHA arranged or helped in arranging transport facility the probability of institutional delivery is increased by 1.67 times (p<0.01) than if she is not arranging transport facility. Further if ASHA facilitated to get JSY card to the pregnant women probability of going for full ANC is increases by 1.36 times (p<0.05) than reference. However if ASHA discuses about institutional delivery and approaches to get register than probability of getting TT injection is 1.88 and 1.64 times (p<0.01) higher than that if she did not discus. Further, Probability of benefits from JSY schemes is 1.25 times (p<0.001) higher among women who get married after 18 years. The probability of benefits from JSY schemes is 1.25 times (p<0.001) higher among women who get married after 18 year of age than before 18 years, it is also 1.28 times (p<0.001) and 1.32 times (p<0.001) higher among women have 1 to 8 year of schooling and with 9 and above years of schooling respectively than the women who never attended school. Those women who are working have 1.13 times (p<0.001) higher probability of getting benefits from JSY scheme than not working women. Surprisingly women belongs to wealthiest quintile are .53times (P<0.001) less aware about JSY scheme. Results conclude that work done by ASHA has great influence on maternal health care utilization in India. But results also show that still substantial numbers of needed population are far from utilization of these services. Place of delivery is significantly influenced by referral and transport facility arranged by ASHA.

Keywords: institutional delivery, JSY beneficiaries, referral faculty, public health

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42 Functional Switching of Serratia marcescens Transcriptional Regulator from Activator to Inhibitor of Quorum Sensing by Exogenous Addition

Authors: Norihiro Kato, Yuriko Takayama

Abstract:

Some gram-negative bacteria enable the simultaneous activation of gene expression involved in N-acylhomoserine lactone (AHL) dependent cell-to-cell communication system. Such regulatory system for the bacterial group behavior is termed as quorum sensing (QS) because a diffusible AHL signal can accumulate around the cell during the increase of the cell density and trigger activation of the sequential QS process. By blocking the QS, the expression of diverse genes related to infection, antibiotic production, and biofilm formation is inhibited. Conditioning of QS by regulation of the DNA-receptor-AHL interaction is a potential target for enhancing host defenses against pathogenicity. We focused on engineered application of transcriptional regulator SpnR produced in opportunistic human pathogen Serratia marcescens. The SpnR can interact with AHL signals at an N-terminal domain and also with a promoter region of a QS target gene at a C-terminal domain. As the initial process of the QS activation, the SpnR forms a complex with the AHL to enhance the expression of pig cluster; the SpnR normally acts as an activator for the expression of the QS-dependent gene. In this research, we attempt to artificially control QS by changing the role of SpnR. The QS-dependent prodigiosin production is expected to inhibit by externally added SpnR in the culture broth of AS-1 strain because the AHL concentration was kept below the threshold by AHL-SpnR complex formation. Maltose-binding protein (MBP)-tagged SpnR (MBP-SpnR) was overexpressed in Escherichia coli and purified using an affinity chromatography equipped with an amylose resin column. The specific interaction between AHL and MBP-SpnR was demonstrated by quartz crystal microbalance (QCM) sensor. AHL with amino end-group was coupled with COOH-terminated self-assembled monolayer prepared on a gold electrode of 27-MHz quartz crystal sensor using water-soluble carbodiimide. After the injection of MBP-SpnR into a cup-type sensor cell filled with the buffer solution, time course of resonant frequency change (ΔFs) was determined. A decrease of ΔFs clearly showed the uptake of MBP-SpnR onto the AHL-immobilized electrode. Furthermore, no binding affinity was observed after the heat-inactivation of MBP-SpnR at 80ºC. These results suggest that MBP-SpnR possesses a specific affinity for AHL. MBP-SpnR was added to the culture medium as an AHL trap to study inhibitory effects on intracellularly accumulated prodigiosin. With approximately 2 µM MBP-SpnR, the amount of prodigiosin induced was half that of the control without any additives. In conclusion, the function of SpnR could be switched by adding it to the cell culture. Exogenously added MBP-SpnR possesses high affinity for AHL derived from cells and acts as an inhibitor of AHL-mediated QS.

Keywords: intracellular signaling, microbial biotechnology, quorum sensing, transcriptional regulator

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41 Waste Burial to the Pressure Deficit Areas in the Eastern Siberia

Authors: L. Abukova, O. Abramova, A. Goreva, Y. Yakovlev

Abstract:

Important executive decisions on oil and gas production stimulation in Eastern Siberia have been recently taken. There are unique and large fields of oil, gas, and gas-condensate in Eastern Siberia. The Talakan, Koyumbinskoye, Yurubcheno-Tahomskoye, Kovykta, Chayadinskoye fields are supposed to be developed first. It will result in an abrupt increase in environmental load on the nature of Eastern Siberia. In Eastern Siberia, the introduction of ecological imperatives in hydrocarbon production is still realistic. Underground water movement is the one of the most important factors of the ecosystems condition management. Oil and gas production is associated with the forced displacement of huge water masses, mixing waters of different composition, and origin that determines the extent of anthropogenic impact on water drive systems and their protective reaction. An extensive hydrogeological system of the depression type is identified in the pre-salt deposits here. Pressure relieve here is steady up to the basement. The decrease of the hydrodynamic potential towards the basement with such a gradient resulted in reformation of the fields in process of historical (geological) development of the Nepsko-Botuobinskaya anteclise. The depression hydrodynamic systems are characterized by extremely high isolation and can only exist under such closed conditions. A steady nature of water movement due to a strictly negative gradient of reservoir pressure makes it quite possible to use environmentally-harmful liquid substances instead of water. Disposal of the most hazardous wastes is the most expedient in the deposits of the crystalline basement in certain structures distant from oil and gas fields. The time period for storage of environmentally-harmful liquid substances may be calculated by means of the geological time scales ensuring their complete prevention from releasing into environment or air even during strong earthquakes. Disposal of wastes of chemical and nuclear industries is a matter of special consideration. The existing methods of storage and disposal of wastes are very expensive. The methods applied at the moment for storage of nuclear wastes at the depth of several meters, even in the most durable containers, constitute a potential danger. The enormous size of the depression system of the Nepsko-Botuobinskaya anteclise makes it possible to easily identify such objects at the depth below 1500 m where nuclear wastes will be stored indefinitely without any environmental impact. Thus, the water drive system of the Nepsko-Botuobinskaya anteclise is the ideal object for large-volume injection of environmentally harmful liquid substances even if there are large oil and gas accumulations in the subsurface. Specific geological and hydrodynamic conditions of the system allow the production of hydrocarbons from the subsurface simultaneously with the disposal of industrial wastes of oil and gas, mining, chemical, and nuclear industries without any environmental impact.

Keywords: Eastern Siberia, formation pressure, underground water, waste burial

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40 The Improved Therapeutic Effect of Trans-Cinnamaldehyde on Adipose-Derived Stem Cells without Chemical Induction

Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou

Abstract:

Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.

Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis

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39 Human Dental Pulp Stem Cells Attenuate Streptozotocin-Induced Parotid Gland Injury in Rats

Authors: Gehan ElAkabawy

Abstract:

Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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38 Risks beyond Cyber in IoT Infrastructure and Services

Authors: Mattias Bergstrom

Abstract:

Significance of the Study: This research will provide new insights into the risks with digital embedded infrastructure. Through this research, we will analyze each risk and its potential negation strategies, especially for AI and autonomous automation. Moreover, the analysis that is presented in this paper will convey valuable information for future research that can create more stable, secure, and efficient autonomous systems. To learn and understand the risks, a large IoT system was envisioned, and risks with hardware, tampering, and cyberattacks were collected, researched, and evaluated to create a comprehensive understanding of the potential risks. Potential solutions have then been evaluated on an open source IoT hardware setup. This list shows the identified passive and active risks evaluated in the research. Passive Risks: (1) Hardware failures- Critical Systems relying on high rate data and data quality are growing; SCADA systems for infrastructure are good examples of such systems. (2) Hardware delivers erroneous data- Sensors break, and when they do so, they don’t always go silent; they can keep going, just that the data they deliver is garbage, and if that data is not filtered out, it becomes disruptive noise in the system. (3) Bad Hardware injection- Erroneous generated sensor data can be pumped into a system by malicious actors with the intent to create disruptive noise in critical systems. (4) Data gravity- The weight of the data collected will affect Data-Mobility. (5) Cost inhibitors- Running services that need huge centralized computing is cost inhibiting. Large complex AI can be extremely expensive to run. Active Risks: Denial of Service- It is one of the most simple attacks, where an attacker just overloads the system with bogus requests so that valid requests disappear in the noise. Malware- Malware can be anything from simple viruses to complex botnets created with specific goals, where the creator is stealing computer power and bandwidth from you to attack someone else. Ransomware- It is a kind of malware, but it is so different in its implementation that it is worth its own mention. The goal with these pieces of software is to encrypt your system so that it can only be unlocked with a key that is held for ransom. DNS spoofing- By spoofing DNS calls, valid requests and data dumps can be sent to bad destinations, where the data can be extracted for extortion or to corrupt and re-inject into a running system creating a data echo noise loop. After testing multiple potential solutions. We found that the most prominent solution to these risks was to use a Peer 2 Peer consensus algorithm over a blockchain to validate the data and behavior of the devices (sensors, storage, and computing) in the system. By the devices autonomously policing themselves for deviant behavior, all risks listed above can be negated. In conclusion, an Internet middleware that provides these features would be an easy and secure solution to any future autonomous IoT deployments. As it provides separation from the open Internet, at the same time, it is accessible over the blockchain keys.

Keywords: IoT, security, infrastructure, SCADA, blockchain, AI

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37 The Hidden Mechanism beyond Ginger (Zingiber officinale Rosc.) Potent in vivo and in vitro Anti-Inflammatory Activity

Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

Abstract:

Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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36 Methodology for Risk Assessment of Nitrosamine Drug Substance Related Impurities in Glipizide Antidiabetic Formulations

Authors: Ravisinh Solanki, Ravi Patel, Chhaganbhai Patel

Abstract:

Purpose: The purpose of this study is to develop a methodology for the risk assessment and evaluation of nitrosamine impurities in Glipizide antidiabetic formulations. Nitroso compounds, including nitrosamines, have emerged as significant concerns in drug products, as highlighted by the ICH M7 guidelines. This study aims to identify known and potential sources of nitrosamine impurities that may contaminate Glipizide formulations and assess their presence. By determining observed or predicted levels of these impurities and comparing them with regulatory guidance, this research will contribute to ensuring the safety and quality of combination antidiabetic drug products on the market. Factors contributing to the presence of genotoxic nitrosamine contaminants in glipizide medications, such as secondary and tertiary amines, and nitroso group-complex forming molecules, will be investigated. Additionally, conditions necessary for nitrosamine formation, including the presence of nitrosating agents, and acidic environments, will be examined to enhance understanding and mitigation strategies. Method: The methodology for the study involves the implementation of the N-Nitroso Acid Precursor (NAP) test, as recommended by the WHO in 1978 and detailed in the 1980 International Agency for Research on Cancer monograph. Individual glass vials containing equivalent to 10mM quantities of Glipizide is prepared. These compounds are dissolved in an acidic environment and supplemented with 40 mM NaNO2. The resulting solutions are maintained at a temperature of 37°C for a duration of 4 hours. For the analysis of the samples, an HPLC method is employed for fit-for-purpose separation. LC resolution is achieved using a step gradient on an Agilent Eclipse Plus C18 column (4.6 X 100 mm, 3.5µ). Mobile phases A and B consist of 0.1% v/v formic acid in water and acetonitrile, respectively, following a gradient mode program. The flow rate is set at 0.6 mL/min, and the column compartment temperature is maintained at 35°C. Detection is performed using a PDA detector within the wavelength range of 190-400 nm. To determine the exact mass of formed nitrosamine drug substance related impurities (NDSRIs), the HPLC method is transferred to LC-TQ-MS/MS with the same mobile phase composition and gradient program. The injection volume is set at 5 µL, and MS analysis is conducted in Electrospray Ionization (ESI) mode within the mass range of 100−1000 Daltons. Results: The samples of NAP test were prepared according to the protocol. The samples were analyzed using HPLC and LC-TQ-MS/MS identify possible NDSRIs generated in different formulations of glipizide. It was found that the NAP test generated a various NDSRIs. The new finding, which has not been reported yet, discovered contamination of Glipizide. These NDSRIs are categorised based on the predicted carcinogenic potency and recommended its acceptable intact in medicines. The analytical method was found specific and reproducible.

Keywords: NDSRI, nitrosamine impurities, antidiabetic, glipizide, LC-MS/MS

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35 Identification and Understanding of Colloidal Destabilization Mechanisms in Geothermal Processes

Authors: Ines Raies, Eric Kohler, Marc Fleury, Béatrice Ledésert

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In this work, the impact of clay minerals on the formation damage of sandstone reservoirs is studied to provide a better understanding of the problem of deep geothermal reservoir permeability reduction due to fine particle dispersion and migration. In some situations, despite the presence of filters in the geothermal loop at the surface, particles smaller than the filter size (<1 µm) may surprisingly generate significant permeability reduction affecting in the long term the overall performance of the geothermal system. Our study is carried out on cores from a Triassic reservoir in the Paris Basin (Feigneux, 60 km Northeast of Paris). Our goal is to first identify the clays responsible for clogging, a mineralogical characterization of these natural samples was carried out by coupling X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). The results show that the studied stratigraphic interval contains mostly illite and chlorite particles. Moreover, the spatial arrangement of the clays in the rocks as well as the morphology and size of the particles, suggest that illite is more easily mobilized than chlorite by the flow in the pore network. Thus, based on these results, illite particles were prepared and used in core flooding in order to better understand the factors leading to the aggregation and deposition of this type of clay particles in geothermal reservoirs under various physicochemical and hydrodynamic conditions. First, the stability of illite suspensions under geothermal conditions has been investigated using different characterization techniques, including Dynamic Light Scattering (DLS) and Scanning Transmission Electron Microscopy (STEM). Various parameters such as the hydrodynamic radius (around 100 nm), the morphology and surface area of aggregates were measured. Then, core-flooding experiments were carried out using sand columns to mimic the permeability decline due to the injection of illite-containing fluids in sandstone reservoirs. In particular, the effects of ionic strength, temperature, particle concentration and flow rate of the injected fluid were investigated. When the ionic strength increases, a permeability decline of more than a factor of 2 could be observed for pore velocities representative of in-situ conditions. Further details of the retention of particles in the columns were obtained from Magnetic Resonance Imaging and X-ray Tomography techniques, showing that the particle deposition is nonuniform along the column. It is clearly shown that very fine particles as small as 100 nm can generate significant permeability reduction under specific conditions in high permeability porous media representative of the Triassic reservoirs of the Paris basin. These retention mechanisms are explained in the general framework of the DLVO theory

Keywords: geothermal energy, reinjection, clays, colloids, retention, porosity, permeability decline, clogging, characterization, XRD, SEM-EDS, STEM, DLS, NMR, core flooding experiments

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34 An Adaptable Semi-Numerical Anisotropic Hyperelastic Model for the Simulation of High Pressure Forming

Authors: Daniel Tscharnuter, Eliza Truszkiewicz, Gerald Pinter

Abstract:

High-quality surfaces of plastic parts can be achieved in a very cost-effective manner using in-mold processes, where e.g. scratch resistant or high gloss polymer films are pre-formed and subsequently receive their support structure by injection molding. The pre-forming may be done by high-pressure forming. In this process, a polymer sheet is heated and subsequently formed into the mold by pressurized air. Due to the heat transfer to the cooled mold the polymer temperature drops below its glass transition temperature. This ensures that the deformed microstructure is retained after depressurizing, giving the sheet its final formed shape. The development of a forming process relies heavily on the experience of engineers and trial-and-error procedures. Repeated mold design and testing cycles are however both time- and cost-intensive. It is, therefore, desirable to study the process using reliable computer simulations. Through simulations, the construction of the mold and the effect of various process parameters, e.g. temperature levels, non-uniform heating or timing and magnitude of pressure, on the deformation of the polymer sheet can be analyzed. Detailed knowledge of the deformation is particularly important in the forming of polymer films with integrated electro-optical functions. Care must be taken in the placement of devices, sensors and electrical and optical paths, which are far more sensitive to deformation than the polymers. Reliable numerical prediction of the deformation of the polymer sheets requires sophisticated material models. Polymer films are often either transversely isotropic or orthotropic due to molecular orientations induced during manufacturing. The anisotropic behavior affects the resulting strain field in the deformed film. For example, parts of the same shape but different strain fields may be created by varying the orientation of the film with respect to the mold. The numerical simulation of the high-pressure forming of such films thus requires material models that can capture the nonlinear anisotropic mechanical behavior. There are numerous commercial polymer grades for the engineers to choose from when developing a new part. The effort required for comprehensive material characterization may be prohibitive, especially when several materials are candidates for a specific application. We, therefore, propose a class of models for compressible hyperelasticity, which may be determined from basic experimental data and which can capture key features of the mechanical response. Invariant-based hyperelastic models with a reduced number of invariants are formulated in a semi-numerical way, such that the models are determined from a single uniaxial tensile tests for isotropic materials, or two tensile tests in the principal directions for transversely isotropic or orthotropic materials. The simulation of the high pressure forming of an orthotropic polymer film is finally done using an orthotropic formulation of the hyperelastic model.

Keywords: hyperelastic, anisotropic, polymer film, thermoforming

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33 Prevention and Treatment of Hay Fever Prevalence by Natural Products: A Phytochemistry Study on India and Iran

Authors: Tina Naser Torabi

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Prevalence of allergy is affected by different factors according to its base and seasonal weather changes, and it also needs various treatments.Although reasons of allergy existence are not clear but generally, allergens cause reaction between antigen and antibody because of their antigenic traits. In this state, allergens cause immune system to make mistake and identify safe material as threat, therefore function of immune system impaired because of histamine secretion. There are different reasons for allergy, but herbal reasons are on top of the list, although animal causes cannot be ignored. Important point is that allergenic compounds, cause making dedicated antibody, so in general every kind of allergy is different from the other one. Therefore, most of the plants in herbal allergenic category can cause various allergies for human beings, such as respiratory allergies, nutritional allergies, injection allergies, infection allergies, touch allergies, that each of them show different symptoms based on the reason of allergy and also each of them requires different prevention and treatment. Geographical condition is another effective factor in allergy. Seasonal changes, weather condition, herbal coverage variety play important roles in different allergies. It goes without saying that humid climate and herbal coverage variety in different seasons especially spring cause most allergies in human beings in Iran and India that are discussed in this article. These two countries are good choices for allergy prevalence because of their condition, various herbal coverage, human and animal factors. Hay fever is one of the allergies, although the reasons of its prevalence are unknown yet. It is one of the most popular allergies in Iran and India because of geographical, human, animal and herbal factors. Hay fever is on top of the list in these two countries. Significant point about these two countries is that herbal factor is the most important factor in prevalence of hay fever. Variety of herbal coverage especially in spring during herbal pollination is the main reason of hay fever prevalence in these two countries. Based on the research result of Pharmacognosy and Phytochemistry, pollination of some plants in spring is major reason of hay fever prevalence in these countries. If airborne pollens in pollination season enter the human body through air, they will cause allergic reactions in eyes, nasal mucosa, lungs, and respiratory system, and if these particles enter the body of potential person through food, they will cause allergic reactions in mouth, stomach, and other digestive systems. Occasionally, chemical materials produced by human body such as Histamine cause problems like: developing of nasal polyps, nasal blockage, sleep disturbance, risk of asthma developing, blood vasodilation, sneezing, eye tears, itching and swelling of eyes and nasal mucosa, Urticaria, decrease in blood pressure, and rarely trauma, anesthesia, anaphylaxis and finally death. This article is going to study the reasons of hay fever prevalence in Iran and India and presents prevention and treatment Method from Phytochemistry and Pharmocognocy point of view by using local natural products in these two countries.

Keywords: hay fever, India, Iran, natural treatment, phytochemistry

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