Search results for: end stage kidney disease
6633 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Apoptotic Factors
Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli
Abstract:
Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.Keywords: methotrexate, pioglitazone, endothelium, kidney
Procedia PDF Downloads 3066632 Epileptic Seizures in Patients with Multiple Sclerosis
Authors: Anat Achiron
Abstract:
Background: Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system in young adults. It involves the immune system attacking the protective covering of nerve fibers (myelin), leading to inflammation and damage. MS can result in various neurological symptoms, such as muscle weakness, coordination problems, and sensory disturbances. Seizures are not common in MS, and the frequency is estimated between 0.4 to 6.4% over the disease course. Objective: Investigate the frequency of seizures in individuals with multiple sclerosis and to identify associated risk factors. Methods: We evaluated the frequency of seizures in a large cohort of 5686 MS patients followed at the Sheba Multiple Sclerosis Center and studied associated risk factors and comorbidities. Our research was based on data collection using a cohort study design. We applied logistic regression analysis to assess the strength of associations. Results: We found that younger age at onset, longer disease duration, and prolonged time to immunomodulatory treatment initiation were associated with increased risk for seizures. Conclusions: Our findings suggest that seizures in people with MS are directly related to the demyelination process and not associated with other factors like medication side effects or comorbid conditions. Therefore, initiating immunomodulatory treatment early in the disease course could reduce not only disease activity but also decrease seizure risk.Keywords: epilepsy, seizures, multiple sclerosis, white matter, age
Procedia PDF Downloads 606631 Effect of Maturation on the Characteristics and Physicochemical Properties of Banana and Its Starch
Authors: Chien-Chun Huang, P. W. Yuan
Abstract:
Banana is one of the important fruits which constitute a valuable source of energy, vitamins and minerals and an important food component throughout the world. The fruit ripening and maturity standards vary from country to country depending on the expected shelf life of market. During ripening there are changes in appearance, texture and chemical composition of banana. The changes of component of banana during ethylene-induced ripening are categorized as nutritive values and commercial utilization. The objectives of this study were to investigate the changes of chemical composition and physicochemical properties of banana during ethylene-induced ripening. Green bananas were harvested and ripened by ethylene gas at low temperature (15℃) for seven stages. At each stage, banana was sliced and freeze-dried for banana flour preparation. The changes of total starch, resistant starch, chemical compositions, physicochemical properties, activity of amylase, polyphenolic oxidase (PPO) and phenylalanine ammonia lyase (PAL) of banana were analyzed each stage during ripening. The banana starch was isolated and analyzed for gelatinization properties, pasting properties and microscopic appearance each stage of ripening. The results indicated that the highest total starch and resistant starch content of green banana were 76.2% and 34.6%, respectively at the harvest stage. Both total starch and resistant starch content were significantly declined to 25.3% and 8.8%, respectively at the seventh stage. Soluble sugars content of banana increased from 1.21% at harvest stage to 37.72% at seventh stage during ethylene-induced ripening. Swelling power of banana flour decreased with the progress of ripening stage, but solubility increased. These results strongly related with the decreases of starch content of banana flour during ethylene-induced ripening. Both water insoluble and alcohol insoluble solids of banana flour decreased with the progress of ripening stage. Both activity of PPO and PAL increased, but the total free phenolics content decreased, with the increases of ripening stages. As ripening stage extended, the gelatinization enthalpy of banana starch significantly decreased from 15.31 J/g at the harvest stage to 10.55 J/g at the seventh stage. The peak viscosity and setback increased with the progress of ripening stages in the pasting properties of banana starch. The highest final viscosity, 5701 RVU, of banana starch slurry was found at the seventh stage. The scanning electron micrograph of banana starch showed the shapes of banana starch appeared to be round and elongated forms, ranging in 10-50 μm at the harvest stage. As the banana closed to ripe status, some parallel striations were observed on the surface of banana starch granular which could be caused by enzyme reaction during ripening. These results inferred that the highest resistant starch was found in the green banana could be considered as a potential application of healthy foods. The changes of chemical composition and physicochemical properties of banana could be caused by the hydrolysis of enzymes during the ethylene-induced ripening treatment.Keywords: maturation of banana, appearance, texture, soluble sugars, resistant starch, enzyme activities, physicochemical properties of banana starch
Procedia PDF Downloads 3106630 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Fas Production
Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli
Abstract:
Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.Keywords: methotrexate, pioglitazone, endothelium, kidney
Procedia PDF Downloads 4916629 Extraction and Analysis of Anthocyanins Contents from Different Stage Flowers of the Orchids Dendrobium Hybrid cv. Ear-Sakul
Authors: Orose Rugchati, Khumthong Mahawongwiriya
Abstract:
Dendrobium hybrid cv. Ear-Sakul has become one of the important commercial commodities in Thailand agricultural industry worldwide, either as potted plants or as cut flowers due to the attractive color produced in flower petals. Anthocyanins are the main flower pigments and responsible for the natural attractive display of petal colors. These pigments play an important role in functionality, such as to attract animal pollinators, classification, and grading of these orchids. Dendrobium hybrid cv. Ear-Sakul has been collected from local area farm in different stage flowers (F1, F2-F5, and F6). Anthocyanins pigment were extracted from the fresh flower by solvent extraction (MeOH–TFA 99.5:0.5v/v at 4ºC) and purification with ethyl acetate. The main anthocyanins components are cyanidin, pelargonidin, and delphinidin. Pure anthocyanin contents were analysis by UV-Visible spectroscopy technique at λ max 535, 520 and 546 nm respectively. The anthocyanins contents were converted in term of monomeric anthocyanins pigment (mg/L). The anthocyanins contents of all sample were compared with standard pigments cyanidin, pelargonidin and delphinidin. From this experiment is a simple extraction and analysis anthocyanins content in different stage of flowers results shown that monomeric anthocyanins pigment contents of different stage flowers (F1, F2-F5 and F6 ): cyanidin – 3 – glucoside (mg/l) are 0.85+0.08, 24.22+0.12 and 62.12+0.6; Pelargonidin 3,5-di- glucoside(mg/l) 10.37+0.12, 31.06+0.8 and 81.58+ 0.5; Delphinidin (mg/l) 6.34+0.17, 18.98+0.56 and 49.87+0.7; and the appearance of extraction pure anthocyanins in L(a, b): 2.71(1.38, -0.48), 1.06(0.39,-0.66) and 2.64(2.71,-3.61) respectively. Dendrobium Hybrid cv. Ear-Sakul could be used as a source of anthocyanins by simple solvent extraction and stage of flowers as a guideline for the prediction amount of main anthocyanins components are cyanidin, pelargonidin, and delphinidin could be application and development in quantities, and qualities with the advantage for food pharmaceutical and cosmetic industries.Keywords: analysis, anthocyanins contents, different stage flowers, Dendrobium Hybrid cv. Ear-Sakul
Procedia PDF Downloads 1466628 A Two Stage Stochastic Mathematical Model for the Tramp Ship Routing with Time Windows Problem
Authors: Amin Jamili
Abstract:
Nowadays, the majority of international trade in goods is carried by sea, and especially by ships deployed in the industrial and tramp segments. This paper addresses routing the tramp ships and determining the schedules including the arrival times to the ports, berthing times at the ports, and the departure times in an operational planning level. In the operational planning level, the weather can be almost exactly forecasted, however in some routes some uncertainties may remain. In this paper, the voyaging times between some of the ports are considered to be uncertain. To that end, a two-stage stochastic mathematical model is proposed. Moreover, a case study is tested with the presented model. The computational results show that this mathematical model is promising and can represent acceptable solutions.Keywords: routing, scheduling, tram ships, two stage stochastic model, uncertainty
Procedia PDF Downloads 4316627 Heavy Metals and Carcinogenic Risk Assessment in Free-Ranged Livestock of Lead-Contaminated Goldmine Communities of Zamfara State, Northern Nigeria
Authors: Sulaiman Rabiu, Muazu Gusau Abubakar, Jafar Usman Zakari
Abstract:
The consumption of meat is of great importance as it provides a good source of proteins and significant amount of essential trace element to the body. However, contamination of meat and meat products with heavy metals is becoming a serious threat to food safety and public health. Therefore, the present study is aimed to evaluate the concentration of some heavy metals in muscles and entrails of free-ranged cattle, sheep and goats. A total of sixty (60) fresh samples of muscles, liver, kidney, small intestines and stomach of free ranged cattle, sheep and goats were collected from abattoirs of different goldmine communities of Anka, Bukkuyum, Maru andTalata-Mafara Local Government Areas of Zamfara State, Nigeria. The samples were digested using 10 mL of a mixed 70% high grade concentration of HNO₃ and 65% HCl (4:1 v/v); the mixture was heated until dense fumes disappeared forming a clear transparent solution and diluted to 50 mL with deionized water. Actual concentrations of Cd, Cr, Cu, Co, As, Ni, Mn, Pb and Zn were determined using Microwave Plasma Atomic Emission Spectrophotometer (MP-AES). From the results obtained, goat liver had the highest mean concentration of lead, arsenic, cobalt and manganese (12.43± 0.31, 14.25±0.32, 3.47± 0.86 and 12.68± 0.92 mg/kg respectively) while goat kidney had the highest concentration of copper and zinc (10.08±0.61 and 24.16±1.30 mg/kg respectively). The highest concentrations of cadmium and nickel were recorded in sheep kidney (7.75± 0.65 and 2.08±0.10 mg/kg respectively). Cattle muscles had the highest chromium concentration than all the organs analysed. The target hazard quotients (THQs) for all the metals were below 1.0, but TR which is a risk indices for carcinogenicity indicates an alarming result that requires stringent control to protect public health.Therefore, intensive public health awareness on the risk associated with contamination of heavy metals in meat should be advocated.Keywords: contamination, goldmine, heavy metals, meat
Procedia PDF Downloads 946626 The Use of Authentic Videos to Change Learners’ Negative Attitudes and Perceptions toward Grammar Learning
Authors: Khaldi Youcef
Abstract:
This investigation seeks to inquire into the effectiveness of using authentic videos for grammar teaching purposes. In this investigation, an English animated situation, Hercules, was used as a type of authentic multimedia to teach a particular grammatical structure, namely conditional sentences. This study also aims at investigating the EFL learners’ attitudes toward grammar learning after being exposed to such an authentic video. To reach that purpose, 56 EFL learners were required ultimately to respond to a questionnaire with an aim to reveal their attitudes towards grammar as a language entity and as a subject for being learned. Then, as a second stage of the investigation, the EFL learners were divided into a control group and an experimental group with 28 learners in each. The first group was taught grammar -conditional sentences- using a deductive-inductive approach, while the second group was exposed to an authentic video to learn conditional sentences. There was a post-lesson stage that included a questionnaire to be answered by learners of each group. The aim of this stage is to capture any change in learners' attitudes shown in the pre-lesson questionnaire. The findings of the first stage revealed learners' negative attitudes towards grammar learning. And the third stage results showed the effectiveness of authentic videos in entirely turning learners' attitudes toward grammar learning to be significantly positive. Also, the utility of authentic videos in highly motivating EFL learners can be deduced. The findings of this survey asserted the need for incorporation and integration of authentic videos in EFL classrooms as they resulted in rising effectively learners’ awareness of grammar and looking at it from a communicative perspective.Keywords: multimedia, authentic videos, negative attitudes, grammar learning, EFL learners
Procedia PDF Downloads 926625 Evaluation of Trabectedin Safety and Effectiveness at a Tertiary Cancer Center at Qatar: A Retrospective Analysis
Authors: Nabil Omar, Farah Jibril, Oraib Amjad
Abstract:
Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring
Procedia PDF Downloads 1296624 Reminiscence Therapy for Alzheimer’s Disease Restrained on Logistic Regression Based Linear Bootstrap Aggregating
Authors: P. S. Jagadeesh Kumar, Mingmin Pan, Xianpei Li, Yanmin Yuan, Tracy Lin Huan
Abstract:
Researchers are doing enchanting research into the inherited features of Alzheimer’s disease and probable consistent therapies. In Alzheimer’s, memories are extinct in reverse order; memories formed lately are more transitory than those from formerly. Reminiscence therapy includes the conversation of past actions, trials and knowledges with another individual or set of people, frequently with the help of perceptible reminders such as photos, household and other acquainted matters from the past, music and collection of tapes. In this manuscript, the competence of reminiscence therapy for Alzheimer’s disease is measured using logistic regression based linear bootstrap aggregating. Logistic regression is used to envisage the experiential features of the patient’s memory through various therapies. Linear bootstrap aggregating shows better stability and accuracy of reminiscence therapy used in statistical classification and regression of memories related to validation therapy, supportive psychotherapy, sensory integration and simulated presence therapy.Keywords: Alzheimer’s disease, linear bootstrap aggregating, logistic regression, reminiscence therapy
Procedia PDF Downloads 3006623 Changes of Chemical Composition and Physicochemical Properties of Banana during Ethylene-Induced Ripening
Authors: Chiun-C.R. Wang, Po-Wen Yen, Chien-Chun Huang
Abstract:
Banana is produced in large quantities in tropical and subtropical areas. Banana is one of the important fruits which constitute a valuable source of energy, vitamins and minerals. The ripening and maturity standards of banana vary from country to country depending on the expected shelf life of market. The compositions of bananas change dramatically during ethylene-induced ripening that are categorized as nutritive values and commercial utilization. Nevertheless, there is few study reporting the changes of physicochemical properties of banana starch during ethylene-induced ripening of green banana. The objectives of this study were to investigate the changes of chemical composition and enzyme activity of banana and physicochemical properties of banana starch during ethylene-induced ripening. Green bananas were harvested and ripened by ethylene gas at low temperature (15℃) for seven stages. At each stage, banana was sliced and freeze-dried for banana flour preparation. The changes of total starch, resistant starch, chemical compositions, physicochemical properties, activity of amylase, polyphenolic oxidase (PPO) and phenylalanine ammonia lyase (PAL) of banana were analyzed each stage during ripening. The banana starch was isolated and analyzed for gelatinization properties, pasting properties and microscopic appearance each stage of ripening. The results indicated that the highest total starch and resistant starch content of green banana were 76.2% and 34.6%, respectively at the harvest stage. Both total starch and resistant starch content were significantly declined to 25.3% and 8.8%, respectively at the seventh stage. Soluble sugars content of banana increased from 1.21% at harvest stage to 37.72% at seventh stage during ethylene-induced ripening. Swelling power of banana flour decreased with the progress of ripening stage, but solubility increased. These results strongly related with the decreases of starch content of banana flour during ethylene-induced ripening. Both water insoluble and alcohol insoluble solids of banana flour decreased with the progress of ripening stage. Both activity of PPO and PAL increased, but the total free phenolics content decreased, with the increases of ripening stages. As ripening stage extended, the gelatinization enthalpy of banana starch significantly decreased from 15.31 J/g at the harvest stage to 10.55 J/g at the seventh stage. The peak viscosity and setback increased with the progress of ripening stages in the pasting properties of banana starch. The highest final viscosity, 5701 RVU, of banana starch slurry was found at the seventh stage. The scanning electron micrograph of banana starch showed the shapes of banana starch appeared to be round and elongated forms, ranging in 10-50 μm at the harvest stage. As the banana closed to ripe status, some parallel striations were observed on the surface of banana starch granular which could be caused by enzyme reaction during ripening. These results inferred that the highest resistant starch was found in the green banana at the harvest stage could be considered as a potential application of healthy foods. The changes of chemical composition and physicochemical properties of banana could be caused by the hydrolysis of enzymes during the ethylene-induced ripening treatment.Keywords: ethylene-induced ripening, banana starch, resistant starch, soluble sugars, physicochemical properties, gelatinization enthalpy, pasting characteristics, microscopic appearance
Procedia PDF Downloads 4676622 Predicting the Diagnosis of Alzheimer’s Disease: Development and Validation of Machine Learning Models
Authors: Jay L. Fu
Abstract:
Patients with Alzheimer's disease progressively lose their memory and thinking skills and, eventually, the ability to carry out simple daily tasks. The disease is irreversible, but early detection and treatment can slow down the disease progression. In this research, publicly available MRI data and demographic data from 373 MRI imaging sessions were utilized to build models to predict dementia. Various machine learning models, including logistic regression, k-nearest neighbor, support vector machine, random forest, and neural network, were developed. Data were divided into training and testing sets, where training sets were used to build the predictive model, and testing sets were used to assess the accuracy of prediction. Key risk factors were identified, and various models were compared to come forward with the best prediction model. Among these models, the random forest model appeared to be the best model with an accuracy of 90.34%. MMSE, nWBV, and gender were the three most important contributing factors to the detection of Alzheimer’s. Among all the models used, the percent in which at least 4 of the 5 models shared the same diagnosis for a testing input was 90.42%. These machine learning models allow early detection of Alzheimer’s with good accuracy, which ultimately leads to early treatment of these patients.Keywords: Alzheimer's disease, clinical diagnosis, magnetic resonance imaging, machine learning prediction
Procedia PDF Downloads 1376621 Better Defined WHO International Classification of Disease Codes for Relapsing Fever Borreliosis, and Lyme Disease Education Aiding Diagnosis, Treatment Improving Human Right to Health
Authors: Mualla McManus, Jenna Luche Thaye
Abstract:
World Health Organisation International Classification of Disease codes were created to define disease including infections in order to guide and educate diagnosticians. Most infectious diseases such as syphilis are clearly defined by their ICD 10 codes and aid/help to educate the clinicians in syphilis diagnosis and treatment globally. However, current ICD 10 codes for relapsing fever Borreliosis and Lyme disease are less clearly defined and can impede appropriate diagnosis especially if the clinician is not familiar with the symptoms of these infectious diseases. This is despite substantial number of scientific articles published in peer-reviewed journals about relapsing fever and Lyme disease. In the USA there are estimated 380,000 people annually contacting Lyme disease, more cases than breast cancer and 6x HIV/AIDS cases. This represents estimated 0.09% of the USA population. If extrapolated to the global population (7billion), 0.09% equates to 63 million people contracting relapsing fever or Lyme disease. In many regions, the rate of contracting some form of infection from tick bite may be even higher. Without accurate and appropriate diagnostic codes, physicians are impeded in their ability to properly care for their patients, leaving those patients invisible and marginalized within the medical system and to those guiding public policy. This results in great personal hardship, pain, disability, and expense. This unnecessarily burdens health care systems, governments, families, and society as a whole. With accurate diagnostic codes in place, robust data can guide medical and public health research, health policy, track mortality and save health care dollars. Better defined ICD codes are the way forward in educating the diagnosticians about relapsing fever and Lyme diseases.Keywords: WHO ICD codes, relapsing fever, Lyme diseases, World Health Organisation
Procedia PDF Downloads 1886620 The Using of Liquefied Petroleum Gas (LPG) on a Low Heat Loss Si Engine
Authors: Hanbey Hazar, Hakan Gul
Abstract:
In this study, Thermal Barrier Coating (TBC) application is performed in order to reduce the engine emissions. Piston, exhaust, and intake valves of a single-cylinder four-cycle gasoline engine were coated with chromium carbide (Cr3C2) at a thickness of 300 µm by using the Plasma Spray coating method which is a TBC method. Gasoline engine was converted into an LPG system. The study was conducted in 4 stages. In the first stage, the piston, exhaust, and intake valves of the gasoline engine were coated with Cr3C2. In the second stage, gasoline engine was converted into the LPG system and the emission values in this engine were recorded. In the third stage, the experiments were repeated under the same conditions with a standard (uncoated) engine and the results were recorded. In the fourth stage, data obtained from both engines were loaded on Artificial Neural Networks (ANN) and estimated values were produced for every revolution. Thus, mathematical modeling of coated and uncoated engines was performed by using ANN. While there was a slight increase in exhaust gas temperature (EGT) of LPG engine due to TBC, carbon monoxide (CO) values decreased.Keywords: LPG fuel, thermal barrier coating, artificial neural network, mathematical modelling
Procedia PDF Downloads 4216619 An Unusual Presentation of Plasmacytoid Urothelial Carcinoma of the Bladder - A Case Report and Literature Review
Authors: Bharti Arora, Michael Chen, Steven Lun
Abstract:
Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review
Procedia PDF Downloads 1486618 Factors Contributing to Delayed Diagnosis and Treatment of Breast Cancer and Its Outcome in Jamhoriat Hospital Kabul, Afghanistan
Authors: Ahmad Jawad Fardin
Abstract:
Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan
Procedia PDF Downloads 1766617 Bayesian Flexibility Modelling of the Conditional Autoregressive Prior in a Disease Mapping Model
Authors: Davies Obaromi, Qin Yongsong, James Ndege, Azeez Adeboye, Akinwumi Odeyemi
Abstract:
The basic model usually used in disease mapping, is the Besag, York and Mollie (BYM) model and which combines the spatially structured and spatially unstructured priors as random effects. Bayesian Conditional Autoregressive (CAR) model is a disease mapping method that is commonly used for smoothening the relative risk of any disease as used in the Besag, York and Mollie (BYM) model. This model (CAR), which is also usually assigned as a prior to one of the spatial random effects in the BYM model, successfully uses information from adjacent sites to improve estimates for individual sites. To our knowledge, there are some unrealistic or counter-intuitive consequences on the posterior covariance matrix of the CAR prior for the spatial random effects. In the conventional BYM (Besag, York and Mollie) model, the spatially structured and the unstructured random components cannot be seen independently, and which challenges the prior definitions for the hyperparameters of the two random effects. Therefore, the main objective of this study is to construct and utilize an extended Bayesian spatial CAR model for studying tuberculosis patterns in the Eastern Cape Province of South Africa, and then compare for flexibility with some existing CAR models. The results of the study revealed the flexibility and robustness of this alternative extended CAR to the commonly used CAR models by comparison, using the deviance information criteria. The extended Bayesian spatial CAR model is proved to be a useful and robust tool for disease modeling and as a prior for the structured spatial random effects because of the inclusion of an extra hyperparameter.Keywords: Besag2, CAR models, disease mapping, INLA, spatial models
Procedia PDF Downloads 2716616 An Auxiliary Technique for Coronary Heart Disease Prediction by Analyzing Electrocardiogram Based on ResNet and Bi-Long Short-Term Memory
Authors: Yang Zhang, Jian He
Abstract:
Heart disease is one of the leading causes of death in the world, and coronary heart disease (CHD) is one of the major heart diseases. Electrocardiogram (ECG) is widely used in the detection of heart diseases, but the traditional manual method for CHD prediction by analyzing ECG requires lots of professional knowledge for doctors. This paper introduces sliding window and continuous wavelet transform (CWT) to transform ECG signals into images, and then ResNet and Bi-LSTM are introduced to build the ECG feature extraction network (namely ECGNet). At last, an auxiliary system for coronary heart disease prediction was developed based on modified ResNet18 and Bi-LSTM, and the public ECG dataset of CHD from MIMIC-3 was used to train and test the system. The experimental results show that the accuracy of the method is 83%, and the F1-score is 83%. Compared with the available methods for CHD prediction based on ECG, such as kNN, decision tree, VGGNet, etc., this method not only improves the prediction accuracy but also could avoid the degradation phenomenon of the deep learning network.Keywords: Bi-LSTM, CHD, ECG, ResNet, sliding window
Procedia PDF Downloads 806615 Inhibition and Breaking of Advanced Glycation End Products with Nuts and Polyphenols
Authors: Moon Ho Do, Sin-Hee Park, Jae Hyuk Lee, Kyo Hee Cho, Jae Kyung Chae, Sun Yeou Kim
Abstract:
Long-term hyperglycemic conditions associated with diabetes lead to the formation of advanced glycation end-products (AGEs). Highly reactive glucose metabolites, methylglyoxal (MGO) and glyoxal (GO), induced carbonyl stress and it may induce cellular damage, cross-linking of proteins, and glycation, playing an important role in the impairment of kidney function. Small molecules that have the ability to inhibit AGE formation, and even break preformed AGEs have a beneficial impact on metabolic syndrome, diabetes, and cancer. We quantified contents of polyphenols in nuts and investigated the protective effect of nuts and polyphenols on MGO-induced cytotoxicity in porcine kidney epithelial cells (LLC-PK1). Moreover, we evaluated the inhibitory effect of AGEs formation in the presence of MGO or GO and possess the ability to break preformed AGEs. In this study, we confirmed twenty polyphenols in diverse nuts using LC-MS/MS system. Nuts and polyphenols play a protective role in LLC-PK1 cells by reducing MGO-induced cytotoxicity. They could also prevent the formation of MGO or GO-mediated AGEs and Break AGEs crosslink. It can be surmised that increased consumption of nuts would be an effective means of preventing diabetic diseases.Keywords: advanced glycation end products, LLC-PK1, methylglyoxal, nut, polyphenol
Procedia PDF Downloads 2596614 Experimentally Validated Analytical Model for Thermal Analysis of Multi-Stage Depressed Collector
Authors: Vishant Gahlaut, A Mercy Latha, Sanjay Kumar Ghosh
Abstract:
Multi-stage depressed collectors (MDC) are used as an efficiency enhancement technique in traveling wave tubes the high-energy electron beam, after its interaction with the RF signal, gets velocity sorted and collected at various depressed electrodes of the MDC. The ultimate goal is to identify an optimum thermal management scheme (cooling mechanism) that could extract the heat efficiently from the electrodes. Careful thermal analysis, incorporating the cooling mechanism is required to ensure that the maximum temperature does not exceed the safe limits. A simple analytical model for quick prediction of the thermal has been developed. The model has been developed for the worst-case un-modulated DC condition, where all the thermal power is dissipated in the last electrode (typically, fourth electrode in the case of the four-stage depressed collector). It considers the thermal contact resistances at various braze joints accounting for the practical non-uniformities. Analytical results obtained from the model have been validated with simulated and experimental results.Keywords: multi-stage depressed collector, TWTs, thermal contact resistance, thermal management
Procedia PDF Downloads 2176613 Impact of Stress and Protein Malnutrition on the Potential Role of Epigallocatechin-3-Gallate in Providing Protection from Nephrotoxicity and Hepatotoxicity Induced by Aluminum in Rats
Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer
Abstract:
Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats
Procedia PDF Downloads 3046612 Comparative Evaluation of Accuracy of Selected Machine Learning Classification Techniques for Diagnosis of Cancer: A Data Mining Approach
Authors: Rajvir Kaur, Jeewani Anupama Ginige
Abstract:
With recent trends in Big Data and advancements in Information and Communication Technologies, the healthcare industry is at the stage of its transition from clinician oriented to technology oriented. Many people around the world die of cancer because the diagnosis of disease was not done at an early stage. Nowadays, the computational methods in the form of Machine Learning (ML) are used to develop automated decision support systems that can diagnose cancer with high confidence in a timely manner. This paper aims to carry out the comparative evaluation of a selected set of ML classifiers on two existing datasets: breast cancer and cervical cancer. The ML classifiers compared in this study are Decision Tree (DT), Support Vector Machine (SVM), k-Nearest Neighbor (k-NN), Logistic Regression, Ensemble (Bagged Tree) and Artificial Neural Networks (ANN). The evaluation is carried out based on standard evaluation metrics Precision (P), Recall (R), F1-score and Accuracy. The experimental results based on the evaluation metrics show that ANN showed the highest-level accuracy (99.4%) when tested with breast cancer dataset. On the other hand, when these ML classifiers are tested with the cervical cancer dataset, Ensemble (Bagged Tree) technique gave better accuracy (93.1%) in comparison to other classifiers.Keywords: artificial neural networks, breast cancer, classifiers, cervical cancer, f-score, machine learning, precision, recall
Procedia PDF Downloads 2706611 Analysis of Cardiovascular Diseases Using Artificial Neural Network
Authors: Jyotismita Talukdar
Abstract:
In this paper, a study has been made on the possibility and accuracy of early prediction of several Heart Disease using Artificial Neural Network. (ANN). The study has been made in both noise free environment and noisy environment. The data collected for this analysis are from five Hospitals. Around 1500 heart patient’s data has been collected and studied. The data is analysed and the results have been compared with the Doctor’s diagnosis. It is found that, in noise free environment, the accuracy varies from 74% to 92%and in noisy environment (2dB), the results of accuracy varies from 62% to 82%. In the present study, four basic attributes considered are Blood Pressure (BP), Fasting Blood Sugar (FBS), Thalach (THAL) and Cholesterol (CHOL.). It has been found that highest accuracy(93%), has been achieved in case of PPI( Post-Permanent-Pacemaker Implementation ), around 79% in case of CAD(Coronary Artery disease), 87% in DCM (Dilated Cardiomyopathy), 89% in case of RHD&MS(Rheumatic heart disease with Mitral Stenosis), 75 % in case of RBBB +LAFB (Right Bundle Branch Block + Left Anterior Fascicular Block), 72% for CHB(Complete Heart Block) etc. The lowest accuracy has been obtained in case of ICMP (Ischemic Cardiomyopathy), about 38% and AF( Atrial Fibrillation), about 60 to 62%.Keywords: coronary heart disease, chronic stable angina, sick sinus syndrome, cardiovascular disease, cholesterol, Thalach
Procedia PDF Downloads 1676610 Impact of Tourists on HIV (Human Immunodeficiency Virus) Incidence
Authors: Ofosuhene O. Apenteng, Noor Azina Ismail
Abstract:
Recently tourism is a major foreign exchange earner in the World. In this paper, we propose the mathematical model to study the impact of tourists on the spread of HIV incidences using compartmental differential equation models. Simulation studies of reproduction number are used to demonstrate new insights on the spread of HIV disease. The periodogram analysis of a time series was used to determine the speed at which the disease is spread. The results indicate that with the persistent flow of tourism into a country, the disease status has increased the epidemic rate. The result suggests that the government must put more control on illegal prostitution, unprotected sexual activity as well as to emphasis on prevention policies that include the safe sexual activity through the campaign by the tourism board.Keywords: HIV/AIDS, mathematical transmission modeling, tourists, stability, simulation
Procedia PDF Downloads 3856609 The Effect of Main Factors on Forces during FSJ Processing of AA2024 Aluminum
Authors: Dunwen Zuo, Yongfang Deng, Bo Song
Abstract:
An attempt is made here to measure the forces of three directions, under conditions of different feed speeds, different tilt angles of tool and without or with the pin on the tool, by using octagonal ring dynamometer in the AA2024 aluminum FSJ (Friction Stir Joining) process, and investigate how four main factors influence forces in the FSJ process. It is found that, high feed speed lead to small feed force and small lateral force, but high feed speed leads to large feed force in the stable joining stage of process. As the rotational speed increasing, the time of axial force drop from the maximum to the minimum required increased in the push-up process. In the stable joining stage, the rotational speed has little effect on the feed force; large rotational speed leads to small lateral force and axial force. The maximum axial force increases as the tilt angle of tool increases at the downward movement stage. At the moment of start feeding, as tilt angle of tool increases, the amplitudes of the axial force increasing become large. In the stable joining stage, with the increase of tilt angle of tool, the axial force is increased, the lateral force is decreased, and the feed force almost unchanged. The tool with pin will decrease axial force in the downward movement stage. The feed force and lateral force will increase, but the axial force will reduced in the stable joining stage by using the tool with pin compare to by using the tool without pin.Keywords: FSJ, force factor, AA2024 aluminum, friction stir joining
Procedia PDF Downloads 4836608 Protective Effect of Wheat Grass (Triticum Durum) against Oxidative Damage Induced by Lead: Study of Some Biomarkers and Histological Few Organs in Males Wistar Rats
Authors: Mansouri Ouarda, Abdennour Cherif, Saidi Malika
Abstract:
Since the industrial revolution, many anthropogenic activities have caused environmental, considerable and overall changes. The lead represents a very dangerous disruptive for the functioning of the body. In this context the current study aims at evaluating a natural therapy by the use of the plant grass in wheat (Triticum durum) against the toxicity of lead in rat wistar male. The rats were divided into three groups: the control group, the group treated with 600 mg /kg food of lead only (Pb) is the group treated with the combination of 600 mg/kg of food and 9g/rat /day of the plant grass in wheat (Pb-bl). The duration of the treatment is 6 weeks. The results of the biometrics of the organs (thyroid, kidney, testis and epididymis) show no significant difference between the three groups. The dosage of a few parameters and hormonal biochemical shows a decrease in the concentration of the hormone T3 and TSH levels among the group pb alone compared to the control and Pb-Bl. These results have been confirmed by the study of histological slices. A morphological changes represented by a shrinking volume of vesicles with the group treated with Pb alone. A return to the normal state of the structure of the follicles was observed. The concentration in serum testosterone, urea and creatinine was significantly increased among the group treated by Pb only in relation to the control and Pb-Bl. whereas the rate of glucose did not show any significant difference. The histology study of the kidney, testis and epididymal weights show no modification at the group Pb-bl comparing to the control. The parenchyma of the kidney shows a dilation of tubes distal and proximal causing a tubular nephropathy for the batch processed by Pb only. The testicles have marked a destruction or absence of germ cells and the light of some seminiferous are almost empty. Conclusion: The supplementation of the plant Triticum durum has caused a considerable improvement which ensures the return of parameters investigated in the normal state.Keywords: creatinine, glucose, histological sections, T3, TSH, testosterone
Procedia PDF Downloads 3706607 Family Satisfaction with Neuro-Linguistic Care for Patients with Alzheimer’s Disease
Authors: Sara Sahraoui
Abstract:
This research studied the effect of Alzheimer's disease (AD) on language information processing in subjects with Alzheimer’s disease (AD) who were bilingual (French and dialectical Arabic). The results show a disorder of certain semantic aspects of their mother tongue (L1). On the other hand, grammatical levels appeared to be relatively unaffected in oral speech in L1 but were disturbed in the second language (L2). In consequence, we constructed a cognitive-language stimulation protocol for bilingual patients (PSCLAB) to respond to this disorder. The efficacy of this protocol in terms of rehabilitation was assessed in 30 such patients through discourse analysis carried out before and after initiating the protocol. The results show that cognitive/language training using the PSCLAB appears to improve the language behaviour of bilingual patients with AD. However, this survey study aims to verify the satisfaction of patients’ relatives with the results of cognitive language training by PSCLAB. We developed a brief instrument to measure the satisfaction of family members. The results report that the patient's relatives are satisfied with the results of cognitive training by PSCLAB.Keywords: satisfaction, Alzheimer's disease, rehabilitation, levels language
Procedia PDF Downloads 686606 Effect of Salinity on Carbon Isotope Discrimination in Chamomile
Authors: Mehdi Ghanavati
Abstract:
The Effects of salinity level and duration on carbon isotope discrimination (Δ) of Matricaria chamomilla and Matricaria aurea were evaluated. Four ecotypes of M. chamomilla and four ecotypes of M. aurea were grown at different NaCl concentrations (control, 6, 12 and 18 dS/m) in sand culture condition. Carbon isotope discrimination (Δ) varied significantly (p<0.001) among ecotypes. The amount of carbon isotope discrimination (Δ) increased in first salinity level (6 dS/m), but in other levels (12 and 18 dS/m) it did not increase. Stages of salinity treatments (two stages: first from seedling stage until the end of the experiment and second stage of stress exertion began at stem elongation and seedlings emergence from rosette stage to harvest) had not a significant difference. Study of two spices of chamomile showed the M. aurea had a higher amount of carbon isotope discrimination (Δ) (22.9%) than M. chamomilla (22.48%).Keywords: salinity, carbon isotope discrimination, Matricaria chamomilla, Matricaria aurea
Procedia PDF Downloads 4356605 Expression of ACSS2 Genes in Peripheral Blood Mononuclear Cells of Patients with Alzheimer’s Disease
Authors: Ali Bayram, Burak Uz, Remzi Yiğiter
Abstract:
The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR
Procedia PDF Downloads 3826604 Identification of Potential Small Molecule Regulators of PERK Kinase
Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl
Abstract:
PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease
Procedia PDF Downloads 474