Search results for: acute and chronic pancreatitis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2222

Search results for: acute and chronic pancreatitis

2102 The 10,000 Fold Effect of Retrograde Neurotransmission, a New Concept for Stroke Revival: Use of Intracarotid Sodium Nitroprusside

Authors: Vinod Kumar

Abstract:

Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

Procedia PDF Downloads 309
2101 A Medical Resource Forecasting Model for Emergency Room Patients with Acute Hepatitis

Authors: R. J. Kuo, W. C. Cheng, W. C. Lien, T. J. Yang

Abstract:

Taiwan is a hyper endemic area for the Hepatitis B virus (HBV). The estimated total number of HBsAg carriers in the general population who are more than 20 years old is more than 3 million. Therefore, a case record review is conducted from January 2003 to June 2007 for all patients with a diagnosis of acute hepatitis who were admitted to the Emergency Department (ED) of a well-known teaching hospital. The cost for the use of medical resources is defined as the total medical fee. In this study, principal component analysis (PCA) is firstly employed to reduce the number of dimensions. Support vector regression (SVR) and artificial neural network (ANN) are then used to develop the forecasting model. A total of 117 patients meet the inclusion criteria. 61% patients involved in this study are hepatitis B related. The computational result shows that the proposed PCA-SVR model has superior performance than other compared algorithms. In conclusion, the Child-Pugh score and echogram can both be used to predict the cost of medical resources for patients with acute hepatitis in the ED.

Keywords: acute hepatitis, medical resource cost, artificial neural network, support vector regression

Procedia PDF Downloads 423
2100 Indoor Air Pollution: A Major Threat to Human Health

Authors: Pooja Rawat, Rakhi Tyagi

Abstract:

Globally, almost 3 billion people rely on biomass (wood, charcoal, dung and crop residues) and coal as their primary source of domestic energy. Cooking and heating with solid fuels on open fire give rise to major pollutants. Women are primarily affected by these pollutants as they spend most of their time in the house. The WHO World Health Report 2002 estimates that indoor air pollution (IAP) is responsible for 2.7% of the loss of disability adjusted life years (DALYs) worldwide and 3.7% in high mortality developing countries. Indoor air pollution has the potential to not only impact health, but also impact the general economic well-being of the household. Exposure to high level of household pollution lead to acute and chronic respiratory conditions (e.g.: pneumonia, chronic obstructive pulmonary disease, lung cancer and cataract). There has been many strategies for reducing IAP like subsidize cleaner fuel technologies, for example use of kerosene rather than traditional biomass fuels. Another example is development, promotion of 'improved cooking stoves'. India, likely ranks second- distributing over 12 million improved stoves in the first seven years of a national program to develop. IAP should be reduced by understanding the welfare effects of reducing IAP within households and to understanding the most cost effective way to reduce it.

Keywords: open fire, indoor pollution, lung diseases, indoor air pollution

Procedia PDF Downloads 298
2099 Integrated Care on Chronic Diseases in Asia-Pacific Countries

Authors: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

Abstract:

Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

Procedia PDF Downloads 135
2098 Analgesia in Acute Traumatic Rib Fractures

Authors: A. Duncan, A. Blake, A. O'Gara, J. Fitzgerald

Abstract:

Introduction: Acute traumatic rib fractures have significant morbidity and mortality and are a commonly seen injury in trauma patients. Rib fracture pain can often be acute and can prove challenging to manage. We performed an audit on patients with acute traumatic rib fractures with the aim of composing a referral and treatment pathway for such patients. Methods: From January 2021 to January 2022, the pain medicine service encouraged early referral of all traumatic rib fractures to the pain service for a multi-modal management approach. A retrospective audit of analgesic management was performed on a select cohort of 24 patients, with a mean age of 67, of which 19 had unilateral rib fractures. Results: 17 of 24 patients (71%) underwent local, regional block as part of a multi-modal analgesia regime. Only one regional complication was observed, seen with hypotension occurring in one patient with a thoracic epidural. The group who did not undergo regional block had a length of stay (LOS) 17 days longer than those who did (27 vs. 10) and higher rates of pneumonia (29% vs. 18%). Conclusion: Early referral to pain specialists is an important component of the effective management of acute traumatic rib fractures. From our audit, it is evident that regional blocks can be effectively used in these cases as part of a multi-modal analgesia regime and may confer benefits in terms of respiratory complications and length of stay.

Keywords: rib fractures, regional blocks, thoracic epidural, erector spina block

Procedia PDF Downloads 76
2097 Anxiety and Depression in Chronic Headache Patients: Major Concern for Community Mental Health

Authors: Neeti Sharma, Harshika Pareek, Prerna Puri, Manika Mohan

Abstract:

The present study is aimed at studying the significant relationship between anxiety and depression in chronic headache patients. Chronic Headache patients coming to the Neurology Unit-1 Outpatient Department of the Sawai Mansingh Hospital (SMS) Jaipur, Rajasthan, were included in this study. The sample consisted of 100 patients (N=100). Initially patients were examined by a physician and then they were assessed for Anxiety and Depression using the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Rating Scale for Depression. The relevant information was recorded on a Performa designed for this purpose comprising of socio-demographic variables like age, gender and triggering factors. The correlation-coefficient indicated a significant positive relationship between the anxiety and depression in chronic headache patients. These findings implicate high prevalence of anxiety and depression in the general population, and also indicate an association between headache and psychological disorders. Many evidences support the anxiety-headache-depression syndrome as a distinct disorder, and the association of co-morbid psychiatric illness with headache intractability. This study highlights the importance of prospective research for studying the developmental course and consequences of headache syndromes. Also, various psychotherapies should be applied to the headache patients so as to treat them, at the onset level of anxiety and depression, with the help of medication.

Keywords: anxiety, chronic headaches, depression, HAM-A, HAM

Procedia PDF Downloads 472
2096 Safety Study of Intravenously Administered Human Cord Blood Stem Cells in the Treatment of Symptoms Related to Chronic Inflammation

Authors: Brian M. Mehling, Louis Quartararo, Marine Manvelyan, Paul Wang, Dong-Cheng Wu

Abstract:

Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) in general represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. Uniquely we have safely and efficiently treated more than 600 patients with documenting each procedure. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Nine patients were treated for conditions associated with chronic inflammation and for the purpose of anti-aging. They have been given one intravenous infusion of UC-MSCs. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.

Keywords: chronic inflammatory diseases, intravenous infusion, stem cell therapy, umbilical cord blood derived mesenchymal stem cells (UC-MSCs)

Procedia PDF Downloads 434
2095 Estimation Cytokines IL-2, IL-4, IL-8 in Serum and Nasal Secretions of Patients with Various Forms of Chronic Polypoid Rhinosinusitis

Authors: U. N. Vokhidov, U. S. Khasanov, A. A. Ismailova

Abstract:

Background: Currently, the researches on the development of chronic polypoid rhinosinusitis cytokines play a major role. The aim of this study was the comparison of indicators IL-2, IL-4, IL-8 in the peripheral blood and nasal secretions of patients with various forms of chronic polypoid rhinosinusitis. Material and methods: We studied 50 patients with chronic polypoid rhinosinusitis receiving hospital treatment in the ENT department of the 3-rd clinic of Tashkent Medical Academy. It was carried out a comprehensive study including morphological examination, immunological study of blood and nasal secretions on the IL-2, IL-4 and IL-8. Results: The results of immunological studies of peripheral blood showed that patients with ‘eosinophilic’ polyps were increased IL-2 and IL-4 in patients with ‘neutrophils’ polyps were increased IL-2 and IL-8. Immunological investigation nasal secretions taken from patients with nasal polyposis rhinosinusitis showed that patients with ‘eosinophilic’ polyps also increased IL- 2 and IL- 4 in patients with ‘neutrophils’ polyps - increased IL-2 and IL-8. Conclusion: In patients with ‘eosinophilic’ polyps revealed the presence of immunity to the allergy of the body, patients with ‘neutrophilic’ polyps identified immunity to the presence of inflammation, it is necessary to take into account the doctor-otolaryngologist when choosing a treatment strategy for the prevention of recurrence of the disease.

Keywords: chronic polypoid rhinosinusitis, immunology, cytikines, nasal secretion

Procedia PDF Downloads 221
2094 Financial Benefits after the Implementation of Antimicrobial Copper in Intensive Care Units (ICUs)

Authors: P. Efstathiou, E. Kouskouni, S. Papanikolaou, K. Karageorgou, Z. Manolidou, Tseroni Maria, A. Efstathiou, V. Karyoti, I. Agrafa

Abstract:

Aim: Aim of this study was to evaluate the reduction on Intensive Care Unit (ICU) microbial flora after the antimicrobial copper alloy (Cu+) implementation as well as the effect on financial-epidemiological operation parameters. Methods: Medical, epidemiological and financial data in two time periods, before and after the implementation of copper (Cu 63% - Zn 37%, low lead) were recorded and analyzed in a general ICU. The evaluated parameters were: the importance of patients' admission (Acute Physiology and Chronic Health Evaluation - APACHE II and Simplified Acute Physiology Score - SAPS), microbial flora's record in the ICU before and after the implementation of Cu+ as well as the impact on epidemiological and ICU's operation financial parameters. Results: During December 2010 and March 2011 and respectively during December 2011 and March 2012 comparative results showed statistically significant reduction on the microbial flora (CFU/ml) by 95% and the use of antimicrobial medicine (per day per patient) by 30% (p = 0,014) as well as patients hospitalization time and cost. Conclusions: The innovative implementation of antimicrobial copper in ICUs contributed to their microbial flora significant reduction and antimicrobial drugs use reduction with the apparent positive effect (decrease) in both patient’s hospitalization time and cost. Under the present circumstances of economic crisis, survey results are of highest importance and value.

Keywords: antimicrobial copper, financial benefits, ICU, cost reduction

Procedia PDF Downloads 471
2093 Effects of Acute Exposure to WIFI Signals (2,45 GHz) on Heart Variability and Blood Pressure in Albinos Rabbit

Authors: Linda Saili, Amel Hanini, Chiraz Smirani, Iness Azzouz, Amina Azzouz, Hafedh Abdemelek, Zihad Bouslama

Abstract:

Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45 GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25 cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+ 22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter the maximum amplitude and P waves. After intravenously injection of dopamine (0.50 ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that WIFI alter catecholamines(dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radio frequency can act directly and/or indirectly on the cardiovascular system.

Keywords: heart rate (HR), arterial pressure (PA), electrocardiogram (ECG), the efficacy of catecholamines, dopamine, epinephrine

Procedia PDF Downloads 452
2092 The Acute Impact of the Intake of Breadsticks from Different Durum Wheat Flour Mixtures on Postprandial Inflammation, Oxidative Stress, and Antiplatelet Activity in Healthy Volunteers: A Pilot Cross-Over Nutritional Intervention

Authors: O. I. Papagianni, P. Potsaki, K. Almpounioti, D. Chatzicharalampous, A. Voutsa, O. Katira, A. Michalaki, H. C. Karantonis, A. E. Koutelidakis

Abstract:

High intakes of carbohydrates and fats have been associated with an increased risk of chronic diseases due to the role of postprandial oxidative stress. This pilot nutritional intervention aimed to examine the acute effect of consuming two different types of breadsticks prepared from durum wheat flour mixtures differing in total phenolic content on postprandial inflammatory and oxidant responses in healthy volunteers. A cross-over, controlled, and single-blind clinical trial was designed, and two isocaloric high-fat and high-carbohydrate meals were tested. Serum total, HDL- and LDL-cholesterol, triglycerides, glucose, CRP, uric acid, plasma total antioxidant capacity, and antiplatelet activity were determined in fasting and 30, 60, and 120 min after consumption. The results showed a better postprandial HDL-cholesterol and total antioxidant activity response in the intervention group. The choice of durum wheat flours with higher phenolic content and antioxidant activity is presented as promising for human health, and clinical studies will expand to draw safer conclusions.

Keywords: breadsticks, durum wheat flours, postprandial inflammation, postprandial oxidative stress, ex vivo antiplatelet activity

Procedia PDF Downloads 78
2091 A Survey of Chronic Pain Patients’ Experiences in the Emergency Department

Authors: G. Fitzpatrick, S. O. Chonghaile, D. Harmon

Abstract:

Objective: Chronic pain patients represent a unique challenge in the Emergency Department. Very little literature has been published regarding this group of patients. Our aim was to determine the attitude of patients with chronic pain to the Emergency Department in order to improve and streamline their future visits. Methods: A two-year survey was carried out on Chronic Pain Patients regarding their Emergency Department Attendances. Patients attending the Pain Clinic in Croom Hospital, Co. Limerick were asked to complete a 20-part questionnaire regarding their experiences of visiting the Emergency Department in the preceding year. 46 questionnaires were completed. Results: Unbearable breakthrough pain was the main reason for visiting the Emergency Department. More than half (54%) of those surveyed were not satisfied with the treatment received. Problems indicated included under-treatment of pain (59%), a sense of being under undue suspicion of drug-seeking behaviour (33%) and a perception that the patient themselves understood their condition better than the treating doctor (76%). Paracetamol, NSAIDs, or time off work comprised 72% of the treatments offered – all of which could have been provided by their General Practitioner. Only 4% were offered a nerve block. 67% felt that the creation of personalised Patient Plans, consisting of an agreed plan between the patient, their pain specialist, and the Emergency Department, would expedite their trip through the Emergency Department. Conclusions: Chronic pain patients generally have a negative experience in the ED. Possible future solutions include increasing our empathy and levels of knowledge, provision of nerve blocks in the ED, and use of personalised “Patient Plans” to streamline the treatment pathway for this group of patients.

Keywords: chronic pain, survey, patients, emergency department

Procedia PDF Downloads 374
2090 [Keynote Talk]: The Emotional Life of Patients with Chronic Diseases: A Framework for Health Promotion Strategies

Authors: Leslie Beale

Abstract:

Being a patient with a chronic disease is both a physical and emotional experience. The ability to recognize a patient’s emotional health is an important part of a health care provider’s skills. For the purposes of this paper, emotional health is viewed as the way that we feel, and the way that our feelings affect us. Understanding the patient’s emotional health leads to improved provider-patient relationships and health outcomes. For example, when a patient first hears his or her diagnosis from a provider, they might find it difficult to cope with their emotions. Struggling to cope with emotions interferes with the patient’s ability to read, understand, and act on health information and services. As a result, the patient becomes more frustrated and confused, creating barriers to accessing healthcare services. These barriers are challenging for both the patient and their healthcare providers. There are five basic emotions that are part of who we are and are always with us: fear, anger, sadness, joy, and compassion. Living with a chronic disease however can cause a patient to experience and express these emotions in new and unique ways. Within the provider-patient relationship, there needs to be an understanding that each patient experiences these five emotions and, experiences them at different times. In response to this need, the paper highlights a health promotion framework for patients with chronic disease. This framework emphasizes the emotional health of patients.

Keywords: health promotion, emotional health, patients with chronic disease, patient-centered care

Procedia PDF Downloads 236
2089 Rainfall–Runoff Simulation Using WetSpa Model in Golestan Dam Basin, Iran

Authors: M. R. Dahmardeh Ghaleno, M. Nohtani, S. Khaledi

Abstract:

Flood simulation and prediction is one of the most active research areas in surface water management. WetSpa is a distributed, continuous, and physical model with daily or hourly time step that explains precipitation, runoff, and evapotranspiration processes for both simple and complex contexts. This model uses a modified rational method for runoff calculation. In this model, runoff is routed along the flow path using Diffusion-Wave equation which depends on the slope, velocity, and flow route characteristics. Golestan Dam Basin is located in Golestan province in Iran and it is passing over coordinates 55° 16´ 50" to 56° 4´ 25" E and 37° 19´ 39" to 37° 49´ 28"N. The area of the catchment is about 224 km2, and elevations in the catchment range from 414 to 2856 m at the outlet, with average slope of 29.78%. Results of the simulations show a good agreement between calculated and measured hydrographs at the outlet of the basin. Drawing upon Nash-Sutcliffe model efficiency coefficient for calibration periodic model estimated daily hydrographs and maximum flow rate with an accuracy up to 59% and 80.18%, respectively.

Keywords: watershed simulation, WetSpa, stream flow, flood prediction

Procedia PDF Downloads 244
2088 Feasibility of Phenolic Acids Rich Fraction from Gynura procumbens as Potential Antihyperlipidemic Agent

Authors: Vikneswaran Murugaiyah, Sultan Ayesh Mohammed Saghir, Kisantini Murugesu, Mohd. Zaini Asmawi, Amirin Sadikun

Abstract:

Gynura procumbens is a popular medicinal plant used as a folk medicine in Southeast Asia to treat kidney diseases, diabetes mellitus and hyperlipidemia. The present study aims to investigate the antihyperlipidemic potential of phenolic acids rich fraction (PARF) from G. procumbens in chemically-induced acute and high fat diet-induced chronic hyperlipidemic rats. Ethanolic extract of G. procumbens leaves exhibited significant reductions in total cholesterol (TC) and triglycerides (TG) levels (P < 0.01 and P < 0.001, respectively) of poloxamer 407-induced rats compared to hyperlipidemic control after 58 h of treatment. Upon bioactivity guided fractionation the antihyperlipidemic activity was found to be concentrated in the PARF, which significantly reduced the TC and TG levels (P < 0.001). HPLC analysis revealed that 3,5-dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid and chlorogenic acid are the major compounds in the PARF. Likewise, chlorogenic acid (60 mg/kg) exhibited significant reductions in TC and TG levels of hyperlipidemic rats (P < 0.001). Both chlorogenic acid and PARF significantly reduced LDL, VLDL and atherogenic index (P<0.01), while PARF increased the HDL (P < 0.01) compared to hyperlipidemic control. Both were found to be not cytotoxic against normal and cancer cell lines. In addition, LD50 of orally administered PARF was more than 5,000 mg/kg. Further investigation in high fat diet-induced chronic hyperlipidemic rats revealed that chronic administration of PARF dose-dependently restored the increase in lipids parameters. In summary, the phenolic acids rich fraction of G. procumbens leaves showed promising antihyperlipidemic effect in both chemically- and diet-induced hyperlipidemic rats that warrants further elucidation on its mechanisms of action.

Keywords: Antihyperlipidemic, Gynura procumbens, phenolic acids, chlorogenic acid, poloxamer-407, high fat diet

Procedia PDF Downloads 233
2087 The Use of Venous Glucose, Serum Lactate and Base Deficit as Biochemical Predictors of Mortality in Polytraumatized Patients: Acomparative with Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evalution IV

Authors: Osama Moustafa Zayed

Abstract:

Aim of the work: To evaluate the effectiveness of venous glucose, levels of serum lactate and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients. Compared to the predictive value of Trauma and injury severity (TRISS) and Acute Physiology And Chronic Health Evaluation IV (APACHE IV). Introduction: Trauma is a serious global health problem, accounting for approximately one in 10 deaths worldwide. Trauma accounts for 5 million deaths per year. Prediction of mortality in trauma patients is an important part of trauma care. Several trauma scores have been devised to predict injury severity and risk of mortality. The trauma and injury severity score (TRISS) was most common used. Regardless of the accuracy of trauma scores, is based on an anatomical description of every injury and cannot be assigned to the patients until a full diagnostic procedure has been performed. So we hypothesized that alterations in admission glucose, lactate levels and base deficit would be an early and easy rapid predictor of mortality. Patient and Method: a comparative cross-sectional study. 282 Polytraumatized patients attended to the Emergency Department(ED) of the Suez Canal university Hospital constituted. The period from 1/1/2012 to 1/4/2013 was included. Results: We found that the best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients is = 90, with 77% sensitivity and 89% specificity using area under the ROC curve (0.89) at (95%CI). APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar (RBS) for prediction of mortality was>140 mg/dl, with 89%, sensitivity, 49% specificity. The best cut off value of base deficit for prediction of mortality was less than -5.6 with 64% sensitivity, 93% specificity. The best cutoff point of lactate for prediction of mortality was > 2.6 mmol/L with 92%, sensitivity, 42% specificity. Conclusion: According to our results from all evaluated predictors of mortality (laboratory and scores) and mortality based on the estimated cutoff values using ROC curves analysis, the highest risk of mortality was found using a cutoff value of 90 in TRISS score while with laboratory parameters the highest risk of mortality was with serum lactate > 2.6 . Although that all of the three parameter are accurate in predicting mortality in poly-traumatized patients and near with each other, as in serum lactate the area under the curve 0.82, in BD 0.79 and 0.77 in RBS.

Keywords: APACHE IV, emergency department, polytraumatized patients, serum lactate

Procedia PDF Downloads 295
2086 Assessment of the Neuroprotective Effect of Oral Hypoglycemic Agents in Patients with Acute Ischemic Stroke

Authors: A. Alhusban, M. Alqawasmeh, F. Alfawares

Abstract:

Introduction: Diabetes is a chronic health problem and a major risk factor of stroke. A number of therapeutic modalities exist for diabetes management. It’s still unknown whether the different oral hypoglycemic agents would ameliorate the detrimental effect of diabetes on stroke severity. The objective of this work is to assess the effect of pretreatment with oral hypoglycemic agents, insulin and their combination on stroke severity at presentation. Patients and Methods: Patients admitted to the King Abdullah University Hospital (KAUH)-Jordan with ischemic stroke between January 2015 and December 2016 were evaluated and their comorbid diseases, treatment on admission and their neurologic severity was assessed using the National Institute of Health Stroke Scale (NIHSS) were documented. Stroke severity was compared for non-diabetic patients and diabetic patients treated with different antidiabetic agents. Results: Data from 324 patients with acute stroke was documented. The median age of participants was 69 years. Diabetes was documented in about 50% of the patients. Multinomial regression analysis identified diabetes treatment status as an independent predictor of neurological severity of stroke (p=0.032). Patients treated with oral hypoglycemic agents had a significantly lower NIHSS as compared to nondiabetic patients and insulin treated patients (p < 0.02). The positive effect of oral hypoglycemic agents was blunted by insulin co-treatment. Insulin did not alter the severity of stroke as compared to non-diabetics. Conclusion: Oral hypoglycemic agents may reduce the severity of neurologic deficit of ischemic stroke and may have neuroprotective effect.

Keywords: diabetes, stroke, neuroprotection, oral hypoglycemic agents

Procedia PDF Downloads 165
2085 Pupils´ Questions at School Attendance Beginning and Teachers´ Teaching Strategy

Authors: Marie Pavelková, Hana Lukášová

Abstract:

Pupils´ inquisitiveness at the beginning of their school attendance is reflected by characteristics of the questions they ask. Clearly most of the classroom communication sequences are initiated by the teacher. But the teaching process also includes questions initiated by pupils in the need to satisfy their need for knowledge. The purpose of our research is to present the results of our pre-research strategy of occurrence of pupil-initiated questions in math lessons at the lower elementary school level, and to reveal the extent to which they are influenced by the teacher´s teaching strategy. We used the research methods of direct and indirect observations of fifth year classes in primary school. We focused on questions asked by the pupils in their math lessons. Our research sample for the pre-research observation method was a collection of video recordings available online. We used them for analysing the nature of pupils´ questions identified there. On the basis of the analysis, we hereby present the results concerning the nature of pupils´ questions asked in math lessons on the lower elementary school level. The interpretation of the collected results will be the starting point for the selection of research strategies in the next research stages concerning pupils’ questions in the future.

Keywords: beginning of schooling, pre-research, questions of pupils, teaching strategy

Procedia PDF Downloads 370
2084 Acute Phase Proteins, Proinflammatory Cytokines and Oxidative Stress Biomarkers in Sheep with Pneumonic Pasteurellosis

Authors: Wael M. El-Deeb

Abstract:

The aim of this study was to assess the pathophysiological importance of lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress markers in sheep with pneumonic pasteurellosis. Blood samples were collected from 36 Pasteurellamultocida-infected sheep, together with 20 healthy controls. Samples for bacteriological examination (nasal swabs, bronchoalveolar lavage) were collected from all animals and subjected to bacteriological examinations. Moreover, heart blood and lung samples were collected from the dead pneumonic sheep and subjected also to bacteriological examinations. A lipid profile was determined, along with a blood picture and other biochemical parameters. The acute phase proteins (fibrinogen, haptoglobin, serum amyloid A), the proinflammatory cytokine tumour necrosis factor-alpha, interleukins (IL-1α, IL-1β, IL-6), interferon-gamma and the oxidative stress markers malondialdehyde, super oxide dismutase, glutathione and catalase were also measured. The examined biochemical parameters were increased in the pneumonic sheep, except for cholesterol and high-density lipoprotein cholesterol (HDL-c), which were significantly lower than control group. Acute phase proteins and cytokines were significantly higher in the pneumonic sheep when compared to the healthy sheep. There was a significant increase in the levels of malondialdehyde; however, a significant decrease in the levels of super oxide dismutase, glutathione and catalase was observed. The present study shed the light on the possible pathphysiological role of lipid profile, acute phase proteins (APPs), proinflammatory cytokines and oxidative stress markers in pneumonic pasteurelosis in sheep.

Keywords: acute phase proteins, sheep, pasteurella, interleukins, stress

Procedia PDF Downloads 392
2083 Bilateral Simultaneous Acute Primary Angle Closure Glaucoma: A Remarkable Case

Authors: Nita Nurlaila Kadarwaty

Abstract:

Purpose: This study presents a rare case of bilateral Acute Primary Angle Closure Glaucoma (PACG). Method: A case report of a 64-year-old woman with a good outcome Acute PACG in both eyes who underwent phacotrabeculectomy surgery. Result: A 64-year-old woman complained of acute pain in both eyes, accompanied by decreased vision, photophobia, and seeing halos for three weeks. There was no history of trauma, steroid or other systemic drugs used, or intraocular surgery before. Ophthalmologic examination revealed a right eye (RE) visual acuity of 0.1, left eye (LE) 0.2. RE intraocular pressure (IOP) was 12 mmhg and LE: 36.4 mmHg in medication of timolol maleat ED and acetazolamide oral. Both eyes' anterior segments revealed mixed injection, corneal edema, shallow anterior chamber, posterior synechiae, mid-dilatation pupil with negative pupillary reflection, and cloudy lens without intumescent. There was a glaucomatous optic and closed iridocorneal angle on the gonioscopy. Initial treatments included oral acetazolamide and potassium aspartate 250 mg three times a day, timolol maleate ED 0.5% twice a day, and prednisolone acetate ED 1% four times a day. This patient underwent trabeculectomy, phacoemulsification, and implantation of IOL in both eyes. One week after the surgeries, both eyes showed decreased IOP and good visual improvement. Conclusion: Bilateral simultaneous Acute PACG is generally severe and results in a poor outcome. It causes rapidly progressive visual loss and is often irreversible. Phacotrabeculectomy has more benefits compared to only phacoemulsification for the intervention regarding the reduced IOP post-surgical.

Keywords: acute primary angle closure glaucoma, intraocular pressure, phacotrabeculectomy, glaucoma

Procedia PDF Downloads 73
2082 Meditation Applied to Chronic Pain

Authors: John Davodi, Maryam Davodi-Far

Abstract:

The human body is the most elaborate of all machines and technologies on Earth, while the human mind is the interdependent source that expels and absorbs the five senses: touch, smell, sight, sound, and taste. Meditation is an ancient form of mind power that has many variations. In fact, those who practice meditation may bring about a positive change in their five senses, depending on the aim of the practitioner. This paper examines the research related to meditation and its effects on individuals suffering from chronic pain. Moreover, consideration is given to whether perceptions of pain can be changed by the practice of meditation as well as whether meditation can have a noticeable and long-term positive effect on the human body. Lastly, the paper examines the type of meditation that is best suited to minimize pain sensations for those who suffer from chronic pain.

Keywords: meditation, pain, relaxation, suffering

Procedia PDF Downloads 83
2081 Psychological Stress As A Catalyst For Multiple Sclerosis Progression: Clarifying Pathways From Neural Activation to Immune Dysregulation

Authors: Noah Emil Glisik

Abstract:

Multiple sclerosis (MS) is a chronic, immune-mediated disorder characterized by neurodegenerative processes and a highly variable disease course. Recent research highlights a complex interplay between psychological stress and MS progression, with both acute and chronic stressors linked to heightened inflammatory activity, increased relapse risk, and accelerated disability. This review synthesizes findings from systematic analyses, cohort studies, and neuroimaging investigations to examine how stress contributes to disease dynamics in MS. Evidence suggests that psychological stress influences MS progression through neural and physiological pathways, including dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and heightened activity in specific brain regions, such as the insular cortex. Notably, functional MRI studies indicate that stress-induced neural activity may predict future atrophy in gray matter regions implicated in motor and cognitive function, thus supporting a neurobiological link between stress and neurodegeneration in MS. Longitudinal studies further associate chronic stress with reduced quality of life and higher relapse frequency, emphasizing the need for a multifaceted therapeutic approach that addresses both the physical and psychological dimensions of MS. Evidence from intervention studies suggests that stress management strategies, such as cognitive-behavioral therapy and mindfulness-based programs, may reduce relapse rates and mitigate lesion formation in MS patients. These findings underscore the importance of integrating stress-reducing interventions into standard MS care, with potential to improve disease outcomes and patient well-being. Further research is essential to clarify the causal pathways and develop targeted interventions that could modify the stress response in MS, offering an avenue to address disease progression and enhance quality of life.

Keywords: multiple sclerosis, psychological stress, disease progression, neuroimaging, stress management

Procedia PDF Downloads 14
2080 Studies on Effect of Nano Size and Surface Coating on Enhancement of Bioavailability and Toxicity of Berberine Chloride; A p-gp Substrate

Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

Procedia PDF Downloads 390
2079 Evaluating Gallein Dye as a Beryllium Indicator

Authors: Elise M. Shauf

Abstract:

Beryllium can be found naturally in some fruits and vegetables (carrots, garden peas, kidney beans, pears) at very low concentrations, but is typically not clinically significant due to the low-level exposure and limited absorption of beryllium by the stomach and intestines. However, acute or chronic beryllium exposure can result in harmful toxic and carcinogenic biological effects. Beryllium can be both a workplace hazard and an environmental pollutant, therefore determining the presence of beryllium at trace levels can be essential to protect workers as well as the environment. Analysis of gallein, C₂₀H₁₂O₇, to determine if it is usable as a fluorescent dye for beryllium detection. The primary detection method currently in use includes hydroxybenzoquinoline sulfonates (HBQS), for which alternative indicators are desired. Unfortunately, gallein does not have the desired aspects needed as a dye for beryllium detection due to the peak shift properties.

Keywords: beryllium detection, fluorescent, gallein dye, indicator, spectroscopy

Procedia PDF Downloads 142
2078 A Meta-Analysis on the Efficacy and Safety of TRC101/Veverimer 6g/Day in Increasing Serum Bicarbonate Levels of Chronic Kidney Disease Patients with Metabolic Acidosis

Authors: Hazel Ann Gianelli Cu, Stephanie Co, Radcliff Cobankiat

Abstract:

Objectives: TRC101/Veverimer is an orally administered, non absorbed, sodium- and counterion-free hydrochloric acid binder for the treatment of metabolic acidosis associated with chronic kidney disease. The main objective of this study is to determine the efficacy of TRC 101/ Veverimer 6g/day in increasing serum bicarbonate levels of chronic kidney disease patients with metabolic acidosis. In this meta analysis, we also aim to look at safety outcomes, adverse effects and if the level of serum bicarbonate reached metabolic alkalosis when given TRC101/Veverimer. Methodology: Pubmed, Cochrane, Google Scholar and Science direct were used to search for randomized controlled trials about TRC101/Veverimer use in Chronic kidney disease patients with metabolic acidosis. Search strategy according to the Prisma checklist was done with evaluation of biases and synthesis of results using the Cochrane Review Manager software 5.4. Results: Two randomized controlled trials involving 371 chronic kidney disease patients were included in this study. Results show there was a significant increase in the serum bicarbonate level when given TRC101/Veverimer compared to the placebo. Both studies had a significant number of participants who completed the studies until the end. P value of <0.00001 was used in both studies with a confidence interval of 95%. Conclusion: TRC101/Veverimer 6g/day was shown to effectively and safely increase serum bicarbonate or achieve normalization in chronic kidney disease patients with metabolic acidosis as compared with a placebo. This was associated with delayed progression of kidney disease with improvement of physical functioning, however longer duration of future studies is ideal in order to assess further the long advantages and consequences of TRC 101/Veverimer.

Keywords: chronic kidney disease, metabolic acidosis, Veverimer, TRC101

Procedia PDF Downloads 197
2077 Clara Cell Secretory Protein 16 Serum Level Decreases in Patients with Non-Smoking-Related Chronic Obstructive Pulmonary Diseases (COPD)

Authors: Lian Wu, Mervyn Merrilees

Abstract:

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide problem, characterized by irreversible and progressive airflow obstruction. In New Zealand, it is currently the 4th commonest cause of death and exacerbations of COPD are a frequent cause of admission to hospital. Serum levels of Clara cell secretory protein-16 (CC-16) are believed to represent Clara cell toxicity. More recently, CC-16 has been found to be associated with smoker COPD. It is produced almost exclusively by non-ciliated Clara cells in the airways, and its primary function is to protect the lungs against oxidative stress and carcinogenesis. After acute exposure to cigarette smoke, serum levels of CC-16 become elevated. CC16 is a potent natural immune-suppressor and anti-inflammatory agent. In vitro, CC16 inhibits both monocyte and polymorphonuclear neutrophils chemotaxis and phagocytosis. CC16 also inhibits fibroblast chemotaxis. However, the role of CC-16 in non-smoking related COPD is still not clear. In this study, we investigated serum CC-16 levels in non-smoking related COPD. Methods: We compared non-smoker patients with COPD (FEV1<60% of predicted, FEV1/FVC <0.7, n=100) and individuals with normal lung function FEV1≥ 80% of predicted and FEV1/FVC≥ 0.7, n=80). All subjects had no smoking history. CC-16 was measured by ELISA. Results and conclusion: Serum CC-16 levels are reduced in individuals with non-smoking related COPD, and there is a weak correlation with disease severity in non-smoking related COPD group compared to non-smoker controls.

Keywords: COPD, CC-16, ELISA, non-smoking-related COPD

Procedia PDF Downloads 381
2076 Development of a Pain Detector Using Microwave Radiometry Method

Authors: Nanditha Rajamani, Anirudhaa R. Rao, Divya Sriram

Abstract:

One of the greatest difficulties in treating patients with pain is the highly subjective nature of pain sensation. The measurement of pain intensity is primarily dependent on the patient’s report, often with little physical evidence to provide objective corroboration. This is also complicated by the fact that there are only few and expensive existing technologies (Functional Magnetic Resonance Imaging-fMRI). The need is thus clear and urgent for a reliable, non-invasive, non-painful, objective, readily adoptable, and coefficient diagnostic platform that provides additional diagnostic information to supplement its current regime with more information to assist doctors in diagnosing these patients. Thus, our idea of developing a pain detector was conceived to take a step further the detection and diagnosis of chronic and acute pain.

Keywords: pain sensor, microwave radiometery, pain sensation, fMRI

Procedia PDF Downloads 457
2075 Acute Poisoning Based on Age and Gender Caused by Pharmaceuticals and Therapies That Influence the Nervous System

Authors: Ragy Raafat Gaber Attaalla

Abstract:

Background: We looked at acute poisonings brought on by illegal drugs and pharmaceuticals that influence the nervous system at Assiut University Hospitals. Methods: Between January 2010 and December 2015, we conducted a retrospective examination of patient records from the largest tertiary toxicology referral center in Assiut. We examined the frequency, pattern, and distribution of ages and genders of acute nervous system agent poisoning. Results: 29,083 individuals total—16,657 (57.27%) males and 12,426 (42.73%) females—were included in the current study. Men's and women's median ages were 29 and 26, respectively (p < 0.0001). 10,326 (83.10%) women and 12,071 (72.47%) men under 40 were present (p < 0.001). 44.10% of cases had a history of poisoning, and the majority of cases (69.38% in men and 79.00% in women, p<0.001) were purposeful. Between various age groups and nervous system agents, there were notable variations in the ratios of men and women. The most often used agent for women was alprazolam, whereas methadone was more popular for men. Overall, there was a rising tendency in acute poisoning associated with alcohol and opioids used to treat addiction disorders, but a declining trend with benzodiazepines and antidepressants. Conclusion: Addiction to methadone was widespread, particularly in young males, and the majority of these cases were self-inflicted. Alprazolam and clonazepam poisoning most commonly affect women and males in the 20–29 age range, respectively. Opium was utilized by men over 30 and women over 60. Over half of the deaths were related to illicit narcotics, with opium being the most common. This research could raise awareness and lead to the development of gender- and age-specific local programs for education and prevention.

Keywords: acute poisonings, illegal drugs, pharmaceuticals, nerve system

Procedia PDF Downloads 34
2074 Prediction of Survival Rate after Gastrointestinal Surgery Based on The New Japanese Association for Acute Medicine (JAAM Score) With Neural Network Classification Method

Authors: Ayu Nabila Kusuma Pradana, Aprinaldi Jasa Mantau, Tomohiko Akahoshi

Abstract:

The incidence of Disseminated intravascular coagulation (DIC) following gastrointestinal surgery has a poor prognosis. Therefore, it is important to determine the factors that can predict the prognosis of DIC. This study will investigate the factors that may influence the outcome of DIC in patients after gastrointestinal surgery. Eighty-one patients were admitted to the intensive care unit after gastrointestinal surgery in Kyushu University Hospital from 2003 to 2021. Acute DIC scores were estimated using the new Japanese Association for Acute Medicine (JAAM) score from before and after surgery from day 1, day 3, and day 7. Acute DIC scores will be compared with The Sequential Organ Failure Assessment (SOFA) score, platelet count, lactate level, and a variety of biochemical parameters. This study applied machine learning algorithms to predict the prognosis of DIC after gastrointestinal surgery. The results of this study are expected to be used as an indicator for evaluating patient prognosis so that it can increase life expectancy and reduce mortality from cases of DIC patients after gastrointestinal surgery.

Keywords: the survival rate, gastrointestinal surgery, JAAM score, neural network, machine learning, disseminated intravascular coagulation (DIC)

Procedia PDF Downloads 260
2073 Triple Immunotherapy to Overcome Immune Evasion by Tumors in a Melanoma Mouse Model

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

Procedia PDF Downloads 123