Search results for: acute and chronic pancreatitis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2145

Search results for: acute and chronic pancreatitis

1665 The 10,000 Fold Effect Retrograde Neurotransmission: A Newer Concept for Paraplegia’s Physiological Revival by the Use of Intrathecal Sodium Nitroprusside

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

Abstract:

B-Methylprednisolone-level-1-benefit (20%) usually given in paraplegia (but within 8hrs). Patients wait-long-duration for physiological-recovery. Intrathecal-Sodium-Nitroprusside(ITSNP) has been used-in vasospasm-due-to-subarachnoid-hemorrhage. ITSNP-has been studied-here for wide-window-period-range for-treatment, fast-recovery/affordability. 2- for acute-cases-and 1-mechanism-for chronic-cases, which-are-interrelated, are being-proposed-for-physiological-recovery. retrograde-neurotransmission, vasospasm and long-term-potentiation-(ltp) mechanisms are proposed here for recovery. It’s a case-control-prospective-study. 82paraplegia-patients(10patients taken as control-no superfusion or dextrose5% superfusion and 72patients as ITSNP-group). The mean time for superfusion was 14.11 days. ITSNP administered at a dosage of 0.2 mg/kg bo wt. Pre/post ITSNP monitored by SSEP/MEP. After-2-Hours in ITSNP-group Mean-Change-From-Baseline-Asia Motor/Sensory-Score 13.84%/13.10%, after-24-hours MOTOR-1.27-points decrease(3.77%) and SENSORY 10.5points-increase(6.22%)as compared to Control-group no-change noted upto 24-hours, At-7days ITSNP motor/sensory;11.56%/6.22% as compared to Control-group 7.60/4.48%, At-2-months in ITSNP 27.69%/6.22% as compared to Control-group 16.02/4.5%. SSEP/MEP-documented-improvements-noted. ITSNP, a-swift-acting-drug in treatment-of-paraplegia, is effective within-two-hours(mean-change-MOTOR-13.84% and SENSORY-13.10%) on-mean14.11th postparaplegia-day with a small-detrimental-response after-24-hours which-recovers-fast.

Keywords: paraplegias, intrathecal sodium nitroprusside, retrograde transmission, the 10, 000 fold effect, perforators, vasodilatations, long term potenciations

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1664 Acrylamide-Induced Acute Nephrotoxicity in Rats

Authors: Keivan Jamshidi, Afshin Zahedi

Abstract:

Acrylamide (ACR) has been shown to cause neurotoxic effects in humans and neurotoxic, genotoxic, reproductive, and carcinogenic effects in laboratory animals. To investigate the nephrotoxic effect of Acrylamide (ACR), 50 adult male rats (Wistar, approximately 250 g) housed in polycarbonate boxes as 5 per each, and randomly assigned in 5 groups including 4 exposure groups as A, B, C, and D groups of rats (10 rats per exposure group., total) and were exposed to 0.5, 5, 50, 100 mg/kg ACR per day×11days i.p. respectively. The remaining 10 rats were housed in group (E) as control group. Control rats received daily i.p. injections of 0.9% saline (3ml/kg). On day 12, four rats, were randomly selected, perfused , dissected and proper samples were collected from their kidneys. Results of histopathological studies based on H&E technique did show no morphologic changes in kidneys of rats belong to groups A, B and E, while moderate to severe morphologic changes including glomerular hypercellularity, global pattern of proliferative glomerulonephritis, occupation of capsular space, tubular cell swelling and hyaline cast formation, were observed in different stained sections obtained from the kidneys of rats belong to group, C, and D. This finding, beside neurotoxic, reproductive and carcinogenic effects, seems to indicate for the first time another important aspect of toxic effect of ACR, i.e., acute nephrotoxicity.

Keywords: acrylamide, nephrotoxicity, glomerulonephritis, rats

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1663 The Effect of Eight Weeks of Aerobic Training on Indices of Cardio-Respiratory and Exercise Tolerance in Overweight Women with Chronic Asthma

Authors: Somayeh Negahdari, Mohsen Ghanbarzadeh, Masoud Nikbakht, Heshmatolah Tavakol

Abstract:

Asthma, obesity and overweight are the main factors causing change within the heart and respiratory airways. Asthma symptoms are normally observed during exercising. Epidemiological studies have indicated asthma symptoms occurring due to certain lifestyle habits; for example, a sedentary lifestyle. In this study, eight weeks of aerobic exercises resulted in a positive effect overall in overweight women experiencing mild chronic asthma. The quasi-experimental applied research has been done based on experimental and control groups. The experimental group (seven patients) and control group (n = 7) were graded before and after the test. According to the Borg dyspnea and fatigue Perception Index, the training intensity has determined. Participants in the study performed a sub-maximal aerobic activity schedule (45% to 80% of maximum heart rate) for two months, while the control group (n = 7) stayed away from aerobic exercise. Data evaluation and analysis of covariance compared both the pre-test and post-test with paired t-test at significance level of P≤ 0.05. After eight weeks of exercise, the results of the experimental group show a significant decrease in resting heart rate, systolic blood pressure, minute ventilation, while a significant increase in maximal oxygen uptake and tolerance activity (P ≤ 0.05). In the control group, there was no significant difference in these parameters ((P ≤ 0.05). The results indicate the aerobic activity can strengthen the respiratory muscles, while other physiological factors could result in breathing and heart recovery. Aerobic activity also resulted in favorable changes in cardiovascular parameters, and exercise tolerance of overweight women with chronic asthma.

Keywords: asthma, respiratory cardiac index, exercise tolerance, aerobic, overweight

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1662 DTI Connectome Changes in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage Improve Outcome Classification

Authors: Sarah E. Nelson, Casey Weiner, Alexander Sigmon, Jun Hua, Haris I. Sair, Jose I. Suarez, Robert D. Stevens

Abstract:

Graph-theoretical information from structural connectomes indicated significant connectivity changes and improved acute prognostication in a Random Forest (RF) model in aneurysmal subarachnoid hemorrhage (aSAH), which can lead to significant morbidity and mortality and has traditionally been fraught by poor methods to predict outcome. This study’s hypothesis was that structural connectivity changes occur in canonical brain networks of acute aSAH patients, and that these changes are associated with functional outcome at six months. In a prospective cohort of patients admitted to a single institution for management of acute aSAH, patients underwent diffusion tensor imaging (DTI) as part of a multimodal MRI scan. A weighted undirected structural connectome was created of each patient’s images using Constant Solid Angle (CSA) tractography, with 176 regions of interest (ROIs) defined by the Johns Hopkins Eve atlas. ROIs were sorted into four networks: Default Mode Network, Executive Control Network, Salience Network, and Whole Brain. The resulting nodes and edges were characterized using graph-theoretic features, including Node Strength (NS), Betweenness Centrality (BC), Network Degree (ND), and Connectedness (C). Clinical (including demographics and World Federation of Neurologic Surgeons scale) and graph features were used separately and in combination to train RF and Logistic Regression classifiers to predict two outcomes: dichotomized modified Rankin Score (mRS) at discharge and at six months after discharge (favorable outcome mRS 0-2, unfavorable outcome mRS 3-6). A total of 56 aSAH patients underwent DTI a median (IQR) of 7 (IQR=8.5) days after admission. The best performing model (RF) combining clinical and DTI graph features had a mean Area Under the Receiver Operator Characteristic Curve (AUROC) of 0.88 ± 0.00 and Area Under the Precision Recall Curve (AUPRC) of 0.95 ± 0.00 over 500 trials. The combined model performed better than the clinical model alone (AUROC 0.81 ± 0.01, AUPRC 0.91 ± 0.00). The highest-ranked graph features for prediction were NS, BC, and ND. These results indicate reorganization of the connectome early after aSAH. The performance of clinical prognostic models was increased significantly by the inclusion of DTI-derived graph connectivity metrics. This methodology could significantly improve prognostication of aSAH.

Keywords: connectomics, diffusion tensor imaging, graph theory, machine learning, subarachnoid hemorrhage

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1661 Calcitonin gene-related peptide Receptor Antagonists for Chronic Migraine – Real World Outcomes

Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

Abstract:

Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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1660 The Predictive Value of Micro Rna 451 on the Outcome of Imatinib Treatment in Chronic Myeloid Leukemia Patients

Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

Abstract:

Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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1659 Twist2 Is a Key Regulator of Cell Proliferation in Acute Lymphoblastic Leukaemia

Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

Abstract:

Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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1658 Neuropalliative Care in Patients with Progressive Neurological Disease in Czech Republic: Study Protocol

Authors: R. Bužgová, R. Kozáková, M. Škutová, M. Bar, P. Ressner, P. Bártová

Abstract:

Introduction: Currently, there has been an increasing concern about the provision of palliative care in non-oncological patients in both professional literature and clinical practice. However, there is not much scientific information on how to provide neurological and palliative care together. The main objective of the project is to create and to verify a concept of neuro-palliative and rehabilitative care for patients with selected neurological diseases in an advanced stage of the disease and also to evaluate bio-psychosocial and spiritual needs of these patients and their caregivers related to the quality of life using created standardized tools. Methodology: Triangulation of research methods (qualitative and quantitative) will be used. A concept of care and assessment tools will be developed by analyzing interviews and focus groups. Qualitative data will be analyzed using grounded theory. The concept of care will be tested in the context of the intervention study. Using quantitative analysis, we will assess the effect of an intervention provided on the saturation of needs, quality of life, and quality of care. A research sample will be made up of the patients with selected neurological diseases (Parkinson´s syndrome, motor neuron disease, multiple sclerosis, Huntington’s disease), together with patients´ family members. Based on the results, educational materials and a certified course for health care professionals will be created. Findings: Based on qualitative data analysis, we will propose the concept of integrated care model combining neurological, rehabilitative and specialist palliative care for patients with selected neurological diseases in different settings of care and services. Patients´ needs related to quality of life will be described by newly created and validated measuring tools before the start of intervention (application of neuro-palliative and palliative approach) and then in the time interval. Conclusion: Based on the results, educational materials and a certified course for doctors and health care professionals will be created.

Keywords: multidisciplinary approach, neuropalliative care, research, quality of life

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1657 The X-Ray Response Team: Building a National Health Pre-Hospital Service

Authors: Julian Donovan, Jessica Brealey, Matthew Bowker, Marianne Feghali, Gregory Smith, Lee Thompson, Deborah Henderson

Abstract:

This article details the development of the X-ray response team (XRT), a service that utilises innovative technology to safely deliver acute and elective imaging and medical assessment service in the pre-hospital and community setting. This involves a partnership between Northumbria Healthcare NHS Foundation Trust’s Radiology and Emergency Medicine departments and the North East Ambulance Service to create a multidisciplinary prehospital team. The team committed to the delivery of a two-day acute service every week, alongside elective referrals, starting in November 2020. The service was originally made available to a 15-mile radius surrounding the Northumbria Hospital. Due to demand, this was expanded to include the North Tyneside and Northumberland regions. The target population was specified as frail and vulnerable patients, as well as those deemed to benefit from staying in their own environment. Within the first two months, thirty-six percent of patients assessed were able to stay at home due to the provision of off-site imaging. In the future, this service aims to allow patient transfer directly to an appropriate ward or clinic, bypassing the emergency department to improve the patient journey and reduce emergency care pressures.

Keywords: frailty, imaging, pre-hospital, X-ray

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1656 Secure Texting Used in a Post-Acute Pediatric Skilled Nursing Inpatient Setting: A Multidisciplinary Care Team Driven Communication System with Alarm and Alert Notification Management

Authors: Bency Ann Massinello, Nancy Day, Janet Fellini

Abstract:

Background: The use of an appropriate mode of communication among the multidisciplinary care team members regarding coordination of care is an extremely complicated yet important patient safety initiative. Effective communication among the team members(nursing staff, medical staff, respiratory therapists, rehabilitation therapists, patient-family services team…) become essential to develop a culture of trust and collaboration to deliver the highest quality care to patients are their families. The inpatient post-acute pediatrics, where children and their caregivers come for continuity of care, is no exceptions to the increasing use of text messages as a means to communication among clinicians. One such platform is the Vocera Communications (Vocera Smart Mobile App called Vocera Edge) allows the teams to use the application and share sensitive patient information through an encrypted platform using IOS company provided shared and assigned mobile devices. Objective: This paper discusses the quality initiative of implementing the transition from Vocera Smartbage to Vocera Edge Mobile App, technology advantage, use case expansion, and lessons learned about a secure alternative modality that allows sending and receiving secure text messages in a pediatric post-acute setting using an IOS device. This implementation process included all direct care staff, ancillary teams, and administrative teams on the clinical units. Methods: Our institution launched this transition from voice prompted hands-free Vocera Smartbage to Vocera Edge mobile based app for secure care team texting using a big bang approach during the first PDSA cycle. The pre and post implementation data was gathered using a qualitative survey of about 500 multidisciplinary team members to determine the ease of use of the application and its efficiency in care coordination. The technology was further expanded in its use by implementing clinical alerts and alarms notification using middleware integration with patient monitoring (Masimo) and life safety (Nurse call) systems. Additional use of the smart mobile iPhone use include pushing out apps like Lexicomp and Up to Date to have it readily available for users for evident-based practice in medication and disease management. Results: Successful implementation of the communication system in a shared and assigned model with all of the multidisciplinary teams in our pediatric post-acute setting. In just a 3-monthperiod post implementation, we noticed a 14% increase from 7,993 messages in 6 days in December 2020 to 9,116messages in March 2021. This confirmed that all clinical and non-clinical teams were using this mode of communication for coordinating the care for their patients. System generated data analytics used in addition to the pre and post implementation staff survey for process evaluation. Conclusion: A secure texting option using a mobile device is a safe and efficient mode for care team communication and collaboration using technology in real time. This allows for the settings like post-acute pediatric care areas to be in line with the widespread use of mobile apps and technology in our mainstream healthcare.

Keywords: nursing informatics, mobile secure texting, multidisciplinary communication, pediatrics post acute care

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1655 Pre-Operative Psychological Factors Significantly Add to the Predictability of Chronic Narcotic Use: A Two Year Prospective Study

Authors: Dana El-Mughayyar, Neil Manson, Erin Bigney, Eden Richardson, Dean Tripp, Edward Abraham

Abstract:

Use of narcotics to treat pain has increased over the past two decades and is a contributing factor to the current public health crisis. Understanding the pre-operative risks of chronic narcotic use may be aided through investigation of psychological measures. The objective of the reported study is to determine predictors of narcotic use two years post-surgery in a thoracolumbar spine surgery population, including an array of psychological factors. A prospective observational study of 191 consecutively enrolled adult patients having undergone thoracolumbar spine surgery is presented. Baseline measures of interest included the Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia, Multidimensional Scale for Perceived Social Support (MSPSS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Oswestry Disability Index (ODI), Numeric Rating Scales for back and leg pain (NRS-B/L), SF-12’s Mental Component Summary (MCS), narcotic use and demographic variables. The post-operative measure of interest is narcotic use at 2-year follow-up. Narcotic use is collapsed into binary categories of use and no use. Descriptive statistics are run. Chi Square analysis is used for categorical variables and an ANOVA for continuous variables. Significant variables are built into a hierarchical logistic regression to determine predictors of post-operative narcotic use. Significance is set at α < 0.05. Results: A total of 27.23% of the sample were using narcotics two years after surgery. The regression model included ODI, NRS-Leg, time with condition, chief complaint, pre-operative drug use, gender, MCS, PCS subscale helplessness, and CPAQ subscale pain willingness and was significant χ² (13, N=191)= 54.99; p = .000. The model accounted for 39.6% of the variance in narcotic use and correctly predicted in 79.7% of cases. Psychological variables accounted for 9.6% of the variance over and above the other predictors. Conclusions: Managing chronic narcotic usage is central to the patient’s overall health and quality of life. Psychological factors in the preoperative period are significant predictors of narcotic use 2 years post-operatively. The psychological variables are malleable, potentially allowing surgeons to direct their patients to preventative resources prior to surgery.

Keywords: narcotics, psychological factors, quality of life, spine surgery

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1654 Management of Coronary Heart Disease through Yoga

Authors: Subramaniam Iyer

Abstract:

The most common disease that is pertaining to all human beings is heart-related. The reasons for coronary artery disease are due to lifestyle and eating habits. Due to this, many people mentally become sick, feeling that soon they will die due to their heart problems. This results in stress and anxiety, which has become common amongst all the Indians. Medicines are the commonest curative remedy in India, but it is proposed through this article some remedies through yoga. This article does not guarantee a 100% result, but it is a preventive remedy for coronary artery disease. Yoga is giving a new lease of life to many, so to tackle chronic diseases, it provides remedies that will be lifelong. It is brought to many people by Patanjali. Yoga will provide support to patients having coronary artery disease through its various relevant postures (asanas), which can be done very easily. Yoga does not send a message that if you do it regularly, you will be relieved from a particular disease. If it is performed every day, it will add vital energy for a smooth life, even if you are suffering from any chronic disease. In this article, we will be providing 6 postures (asanas), which can be performed at any time in the day, but the early morning will always be preferred (empty stomach) to get a good result. Secondly, these postures must be implemented after due consultation with your physician. If your physician disapproves, don’t do these postures as it will be harmful to your body.

Keywords: coronary artery, yoga, disease, remedy, medicine

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1653 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell

Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity

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1652 Comparative Study of Propensity for Amyloidogenesis in Male and Female Mice

Authors: Keivan Jamshidi, Afshin Zahedi

Abstract:

Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the propensity for amyloidogenesis in male and female rats on spatio-temporal pattern was evaluated. For this purpose a total of 40 male and female Swiss mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatment groups [ 10 male (Group A1) and 10 female (Group B1) each], and 2 control groups [10 male (Group A2) and 10 female (Group B2) each]. At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen samples of each animal were obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. The data obtained from polarized microscopic quantitative analysis did show significant differences between groups A1 and B1. A preferential expression of reactive amyloidosis is concluded in male, indicating sex differences in amyloidosis.

Keywords: amyloidosis, amyloidogenesis, mice, gender

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1651 Phenotypical and Molecular Characterization of Burkholderia mallei from Horses with Glanders: Preliminary Data

Authors: A. F. C. Nassar, D. K. Tessler, L. Okuda, C. Del Fava, D. P. Chiebao, A. H. C. N. Romaldini, A. P. Alvim, M. J. Sanchez-Vazquez, M. S. Rosa, J. C. Pompei, R. Harakava, M. C. S. Araujo, G. H. F. Marques, E. M. Pituco

Abstract:

Glanders is a zoonotic disease of Equidae caused by the bacterium Burkholderia mallei presented in acute or chronic clinical forms with inflammatory nodules in the respiratory tract, lymphangitis and caseous lymph nodes. There is not a treatment with veterinary drugs to this life-threatening disease; thus, its occurrence must be notified to official animal health services and any infected animal must be eliminated. This study aims to detect B. mallei from horses euthanized in outbreaks of glanders in Brazil, providing a better understanding of the bacterial characteristics and determine a proper protocol for isolation. The work was carried out with the collaboration of the Ministry of Agriculture and the Sao Paulo State Animal Health Department, while its procedures were approved by the Committee of Ethics in Animal Experimentation from the Instituto Biologico (CETEA n°156/2017). To the present time, 16 horses from farms with outbreaks of glanders detected by complement fixation test (CFT) serology method were analyzed. During the necropsy, samples of possibly affected organs (lymph nodes, lungs, heart, liver, spleen, kidneys and trachea) were collected for bacterial isolation, molecular tests and pathology. Isolation was performed using two enriched mediums, a potato infusion agar with 5% sheep blood, 4% glycerol and antibiotics (penicilin100U/ mL), and another with the same ingredients except the antibiotic. A PCR protocol was modified for this study using primers design to identify a region of the Flip gen of B. mallei. Thru isolation, 12.5% (2/16) animals were confirmed positive using only the enriched medium with antibiotic and confirmed by PCR: from mediastinal and submandibular lymph nodes and lungs in one animal and from mediastinal lymph node in the other. The detection of the bacterium using PCR showed positivity of 100% (16/16) horses from 144 samples of organs. Pathology macroscopic lesions observed were catarrhal nasal discharge, fetlock ulcers, emaciation, lymphangitis in limbs, suppurative lymphangitis, lymph node enlargement, star shaped liver, and spleen scars, adherence of the renal capsule, pulmonary hemorrhage, and miliary nodules. Microscopic lesions were suppurative bronchopneumonia with microabscesses and Langhans giant cells in lungs; lymph nodes with abscesses and intense lymphoid reaction; hemosiderosis and abscesses in spleen. Positive samples on PCR will be sequenced later and analyzed comparing with previous records in the literature. A throughout description of the recent acute cases of glanders occurring in Brazil and characterization of the bacterium related will contribute to advances in the knowledge of the pathogenicity, clinical symptoms, and epidemiology of this zoonotic disease. Acknowledgment: This project is sponsored by FAPESP.

Keywords: equines, bacterial isolation, zoonosis, PCR, pathology

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1650 Effect of Salvadora Persica Gel on Clinical and Microbiological Parameters of Chronic Periodontitis

Authors: Tahira Hyder, Saima Quraeshi, Zohaib Akram

Abstract:

Salvadora Persica (SP) is known to have anti-inflammatory, antioxidant, anti-coagulant and anti-bacterial properties that may provide therapeutic benefits in the treatment of chronic periodontitis (CP). The current clinical trial was designed to investigate the clinical and anti-microbial effects of SP gel as an adjunct to scaling and root planning (SRP) in subjects with generalized CP. Sixty-six subjects with CP were randomized allocated into two groups: SRP + SP gel (test group) and SRP only (control group). Clinical parameters (periodontal pocket depth, gingival recession, clinical attachment level, bleeding score and plaque score) were recorded at baseline before SRP and at 6 weeks. At baseline and 6 weeks subgingival plaque samples were collected and periodontopathogen Porphyromonas Gingivalis (Pg) quantified using Real-time Polymerase Chain Reaction (RT-PCR). Both therapies reduced the mean periodontal pocket depth (PPD), plaque score (PS) and bleeding score (BOP) and improved the mean clinical attachment level (CAL) between baseline and 6 weeks. In subjects receiving adjunctive SP gel a statistically significant improvement was observed in BOP at follow-up compared to control group (15.01±3.47% and 22.81±6.81% respectively, p=0.001), while there was no statistically significant difference in periodontal pocket depth, gingival recession, clinical attachment level and plaque score between both groups. The test group displayed significantly greater Pg reduction compared to the control group after 6 weeks. The current study establishes that local delivery of SP gel into periodontal pocket in CP stimulated a significant reduction in bacteria Pg level and an improvement in gingival health, as evident from a reduced bleeding score, when used as an adjunct to SRP.

Keywords: miswak, scaling and root planing, porphyromonas gingivalis, chronic periodontitis

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1649 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia

Authors: Svitlana Antonenko, Gennady Telegeev

Abstract:

Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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1648 4(3H)-Quinazolinone Derivatives' Synthesis and Evaluation as Antimalarial and Anti-Leishmanial Agents

Authors: Alemu Tadesse Feroche

Abstract:

In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.

Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity

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1647 Diagnosis of Rotavirus Infection among Egyptian Children by Using Different Laboratory Techniques

Authors: Mohamed A. Alhammad, Hadia A. Abou-Donia, Mona H. Hashish, Mohamed N. Massoud

Abstract:

Background: Rotavirus is the leading etiologic agent of severe diarrheal disease in infants and young children worldwide. The present study was aimed 1) to detect rotavirus infection as a cause of diarrhoea among children under 5 years of age using the two serological methods (ELISA and LA) and the PCR technique (2) to evaluate the three methodologies used for human RV detection in stool samples. Materials and Methods: This study was carried out on 247 children less than 5 years old, diagnosed clinically as acute gastroenteritis and attending Alexandria University Children Hospital at EL-Shatby. Rotavirus antigen was screened by ELISA and LA tests in all stool samples, whereas only 100 samples were subjected to RT-PCR method for detection of rotavirus RNA. Results: Out of the 247 studied cases with diarrhoea, rotavirus antigen was detected in 83 (33.6%) by ELISA and 73 (29.6%) by LA, while the 100 cases tested by RT-PCR showed that 44% of them had rotavirus RNA. Rotavirus diarrhoea was significantly presented with a marked seasonal peak during autumn and winter (61.4%). Conclusion: The present study confirms the huge burden of rotavirus as a major cause of acute diarrhoea in Egyptian infants and young children. It was concluded that; LA is equal in sensitivity to ELISA, ELISA is more specific than LA, and RT-PCR is more specific than ELISA and LA in diagnosis of rotavirus infection.

Keywords: rotavirus, diarrhea, immunoenzyme techniques, latex fixation tests, RT-PCR

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1646 Understanding ASPECTS of Stroke: Interrater Reliability between Emergency Medicine Physician and Radiologist in a Rural Setup

Authors: Vineel Inampudi, Arjun Prakash, Joseph Vinod

Abstract:

Aims and Objectives: To evaluate the interrater reliability in grading ASPECTS score, between emergency medicine physician at first contact and radiologist among patients with acute ischemic stroke. Materials and Methods: We conducted a retrospective analysis of 86 acute ischemic stroke cases referred to the Department of Radiodiagnosis during November 2014 to January 2016. The imaging (plain CT scan) was performed using GE Bright Speed Elite 16 Slice CT Scanner. ASPECTS score was calculated separately by an emergency medicine physician and radiologist. Interrater reliability for total and dichotomized ASPECTS (≥ 6 and < 6) scores were assessed using statistical analysis (ICC and Cohen ĸ coefficients) on SPSS software (v17.0). Results: Interrater agreement for total and dichotomized ASPECTS was substantial (ICC 0.79 and Cohen ĸ 0.68) between the emergency physician and radiologist. Mean difference in ASPECTS between the two readers was only 0.15 with standard deviation of 1.58. No proportionality bias was detected. Bland Altman plot was constructed to demonstrate the distribution of ASPECT differences between the two readers. Conclusion: Substantial interrater agreement was noted in grading ASPECTS between emergency medicine physician at first contact and radiologist thereby confirming its robustness even in a rural setting.

Keywords: ASPECTS, computed tomography, MCA territory, stroke

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1645 Identification of a Lead Compound for Selective Inhibition of Nav1.7 to Treat Chronic Pain

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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1644 Nephrotoxicity and Hepatotoxicity Induced by Chronic Aluminium Exposure in Rats: Impact of Nutrients Combination versus Social Isolation and Protein Malnutrition

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

Abstract:

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

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

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1643 Unexpected Acute Respiratory Failure following Administration of Rocuronium Bromide during Cesarean Delivery in a Severely Preeclamptic Parturient Treated with Magnesium Sulfate

Authors: Joseph Carl Macalintal, Erlinda Armovit

Abstract:

Magnesium sulfate has been a mainstay in the management of preeclampsia and is associated with a decreased incidence of morbidity and mortality. The syndrome has an unpredictable course, sometimes rapidly evolving to full-blown disease. In patients with deteriorating status, it is indicated to terminate the pregnancy via cesarean section. The anesthesiologists would prefer to have the procedure done under regional anesthesia; however, there may be cases when neuraxial anesthesia is contraindicated, or a general anesthesia would permit prompt delivery of the fetus. A patient with severe preeclampsia was given magnesium sulfate intrapartum, wherein a primary cesarean section was indicated for arrest in cervical dilatation, and was performed under general anesthesia. The patient developed acute respiratory failure and the causes of this occurrence were investigated in this report. It was later found out that neither the hypermagnesemia nor the muscle relaxant alone caused the patient’s condition but the interaction between the two. The patient was managed expectantly at the intensive care unit (ICU) and was eventually extubated during the 1st post-operative day. Knowledge of this drug interaction would allow obstetricians to advise their patients and their family about the possibility of prolonged intubation and ICU admission. This would also bring to the anesthesiologists’ attention the need to decrease the dose of muscle relaxant and to prepare drugs for immediate decurarisation.

Keywords: eclampsia, magnesium sulfate, preeclampsia, rocuronium bromide

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1642 Investigation of Supply and Demand Trends in Diabetes Nutrition Counseling

Authors: Maedeh Gharazi

Abstract:

Distinguishing proof of entrepreneurial open doors in the field of nutrition counseling is a focal issue in utilizing nutrition experts and addressing the needs of patients with chronic diseases better. To this end, this review has been directed keeping in mind the end goal to investigate the supply and interest patterns of diabetes sustenance advising as a fundamental stride toward recognizing the entrepreneurial open doors for nutrition advisors in Tehran, Iran. To execute this expressive overview concentrate on, a survey in light of Likert scale was sent via email to 100 dynamic experts in the field of nutrition counseling services in Tehran, of whom 52 reacted to its inquiries. At that point, the mean estimations of members' reactions were ascertained utilizing SPSS programming and contrasted to each other. The outcome acquired in view of members' reactions uncovered that the requirement for "healthful guiding as a treatment group" was basically not met in diverse age, training and salary gatherings of diabetic patients. Along these lines, nutrition counseling as a treatment group can be considered as a suitable field for entrepreneurial exercises.

Keywords: nutrition counseling, chronic diseases, diabetes, likert scale, SPSS programming

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1641 Effect of Green Coffee Bean Extract on Gentamicin Induced Acute Renal Failure in Rats

Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

Abstract:

Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology

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1640 Carvedilol Ameliorates Potassium Dichromate-Induced Acute Renal Injury in Rats: Plausible Role of Inflammation and Apoptosis

Authors: Bidya Dhar Sahu, Meghana Koneru, R. Shyam Sunder, Ramakrishna Sistla

Abstract:

Environmental and occupational exposure to hexavalent chromium [Cr(VI)] via textile manufacture, metallurgy, spray paints, stainless steel industries, drinking water containing chromium are often known to cause acute renal injury in humans and animals. Nephrotoxicity is the major effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol using rat model of potassium dichromate (K2Cr2O7)-induced nephrotoxicity. Exploration of the underlying mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NF-κB (p65), restored antioxidant and mitochondrial respiratory enzyme activities and attenuated apoptosis related protein expressions in kidney tissues. The serum levels of TNF-α, the renal iNOS and myeloperoxidase activity were significantly decreased in carvedilol pre-treated K2Cr2O7-induced nephrotoxic rats. These results were further supported and confirmed by histological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against K2Cr2O7-induced nephrotoxicity in rats.

Keywords: apoptosis, carvedilol, inflammation, potassium dichromate-induced nephrotoxicity, applied pharmacology

Procedia PDF Downloads 257
1639 Lentiviral-Based Novel Bicistronic Therapeutic Vaccine against Chronic Hepatitis B Induces Robust Immune Response

Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

Abstract:

Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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1638 Drug Sensitivity Pattern of Organisms Causing Suppurative Otitis Media

Authors: Nagat M. Saeed, Mabruka S. Elashheb, Fatma M. Ben Rabaha, Aisha M Edrah

Abstract:

The aim of the study was to determine the type and pattern of antibiotic susceptibility of the pathogenic microorganisms causing chronic suppurative otitis media (CSOM), which could lead to better therapeutic decisions and consequently avoidance of appearance of resistance to specific antibiotics. Most frequently isolated agents were Pseudomonas aeruginosa 28.5%; followed by Staphylococcus aureus 18.2%; proteus mirabilis 13.9%; Providencia stuartti 6.7%; Bacteroides melaninogenicus, Aspergillus sp., candida sp., 4.2% each; and other microorganisms were represented in 3-0.2%. Drug sensitivities pattern of Pseudomonas aeruginosa showed that ciprofloxacin was active against the majority of isolates (93.9%) followed by ceftazidime 86.2%, amikacin 76.2% and gentamicin 40.8%. However, Staphylococcus aureus isolates were resistant to penicillin 72.7%, erythromycin 28.6%, cephalothin 18.2%, cloxacillin 8.3% and ciprofloxacin was active against 96.2% of isolates. The resistance pattern of proteus mirabilis was 55.6% to ampicillin, 47.1% to carbencillin, 29.4% to cephalothin, 14.3% to gentamicin and 4.8% to amikacin while 100% were sensitive to ciprofloxacin. We conclude that ciprofloxacin is the best drug of choice in the treatment of CSOM caused by the common microorganisms.

Keywords: otitis media, chronic suppurative otitis media (CSOM), microorganisms, drug sensitivity

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1637 The Power of “Merkiavelli”: Representations of Angela Merkel in the Portuguese Press (2008-2015)

Authors: Ana Mouro, Ana Ramalheira

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Since 1989, with the Fall of the Berlin Wall, Germany has undergone a profound restructuring political and economic process. When the Euro Crisis broke out, Germany was no longer the “sick man” of Europe. Instead, it had recovered its dominance as the strongest and wealthiest economy within the European Union. With the European Debt Crisis, that has been taking place in the European Union since the end of 2009, Germany´s Chancellor Angela Merkel has gained the power of deciding, so to say, on the fate of the debtor nations, but she neither stands for binding German commitments, nor refuses assistance. A debate on whether Merkel’s hesitation has been deliberated and used as a means of coercion has arisen on international print media, and the Portuguese Press has been no exception. This study, which was conducted by using news reporting, opinion articles, interviews and editorials, published in the Portuguese weekly Expresso and the daily Público, from 2008 to 2015, tries to show how Merkel’s hesitation, depicted in the press by the term “Merkiavelli”, was perceived in Portugal, a country that had to embrace the austerity measures, imposed by the European Central Bank, but defined under Angela Merkel´s leading role.

Keywords: Euro crisis, “Merkiavelli”, cultural studies, Portuguese quality press

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1636 Detection of Bcl2 Polymorphism in Patient with Hepatocellular carcinoma

Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

Abstract:

Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

Procedia PDF Downloads 488