Search results for: sibling’s death
528 Surface Modified Polyamidoamine Dendrimer with Gallic Acid Overcomes Drug Resistance in Colon Cancer Cells HCT-116
Authors: Khushbu Priyadarshi, Chandramani Pathak
Abstract:
Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein
Procedia PDF Downloads 149527 Synthesis, Characterization and Biological Evaluation of Some Pyrazole Derivatives
Authors: Afifa Hafidh, Hedia Chaabane
Abstract:
This work mainly focused on the synthetic strategies and biological activities associated with pyrazoles. Pyrazole derivatives have been successfully synthesized by simple and facile method and studied for their antibacterial activity. These compounds were prepared from pyrazolic difunctional compounds as starting materials, by reaction with salicylic acid, paracetamol and thiosemicarbazide respectively. Structure of all the prepared compounds confirmation were proved using (FT-IR), (1H-NMR) and (13C-NMR) spectra in addition to melting points. The screening of the antimicrobial activity of the pyrazolic derivatives was examined against different microorganisms in the present study. They were screened for their antimicrobial activities against gram positive bacteria, gram negative bacteria and Candida albicans. The synthesized compounds were found to exhibit high antibacterial and antifungal efficiency against several tested bacterial strains, using agar diffusion method and filter paper disc-diffusion method. Ampicillin was used as positive control for all strains except Candida albicans for which Nystatin was used. The obtained results reveal that the antibacterial activity of some pyrazolic derivatives is comparable to that observed for the control samples (Ampicilin and Nystatin), suggesting a strong antibacterial activity. The analysis of these results shows that synthesized products react on the surfaces cell walls that are disrupted. When these products are in contact with the bacteria, they damage the membrane, leading to the perturbation of different cellular processes and then leakage of cytoplasm, resulting in the death of the cells. The results will be presented in details. The obtained products constitute effective antibacterial agents and important compounds for biological systems.Keywords: salicylic acid, antimicrobial activities, antioxidant activity, paracetamol, pyrazole, thiosemicarbazide
Procedia PDF Downloads 173526 Ageing Patterns and Concerns in the Arabian Gulf: A Systematic Review
Authors: Asharaf Abdul Salam
Abstract:
Arabian Gulf countries have norms and rules different from others: having an exodus of male immigrant labor contract holders of age 20-60 years as a floating population. Such a demographic scenario camouflages population ageing. However, it is observed on examining vigilantly, not only in the native population but also in the general population. This research on population ageing in the Arabian Gulf examines ageing scenario and concerns through analyses of international databases (US Census Bureau and United Nations) and national level databases (Censuses and Surveys) apart from a review of published research. Transitions in demography and epidemiology lead to gains in life expectancy and thereby reductions in fertility, leading to ageing of the population in the region. Even after bringing adult immigrants, indices and age pyramids show an increasing ageing trend in the total population, demonstrating an ageing workforce. Besides, the exclusive native population analysis reveals a trend of expansive pyramids (pre-transitional stage) turning to constrictive (transition stage) and cylindrical (post-transition stage) shapes. Age-based indices such as the index of ageing, age dependency ratio, and median age confirm this trend. While the feminine nature of ageing is vivid, gains in life expectancy and causes of death in old age, indicating co-morbidity compression, are concerns to ageing. Preparations are in demand to cope with ageing from different dimensions, as explained in the United Nations Plans of Action. A strategy of strengthening informal care with supportive semi-formal and supplementary formal care networks would alleviate this crisis associated with population ageing.Keywords: total versus native population, indices of ageing, age pyramids, feminine nature, comorbidity compression, strategic interventions
Procedia PDF Downloads 94525 Studying the Effects of Ruta Graveolens on Spontaneous Motor Activity, Skeletal Muscle Tone and Strychnine Induced Convulsions in Albino Mice and Rats
Authors: Shaban Saad, Syed Ahmed, Suher Aburawi, Isabel Fong
Abstract:
Ruta graveolens is a plant commonly found in north Africa and south Europe. It is reported that Ruta graveolens is used traditionally for epilepsy and some other illnesses. The acute and sub-acute effects of alcoholic extract residue were tested for possible anti-epileptic and skeletal muscle relaxation activity. The effect of extract on rat spontaneous motor activity (SMA) was also investigated using open filed. We previously proved the anti convulsant activity of the plant against pentylenetetrazol and electrically induced convulsions. Therefore in this study strychnine was used to induce convulsions in order to explore the mechanism of anti-convulsant activity of the plant. The skeletal muscle relaxation activity of Ruta graveolens was studied using pull-up and rod hanging tests in rats. At concentration of 5%w/v the extract protected mice against strychnine induced myoclonic jerks and death. The pull-up and rod hanging tests pointed to a skeletal muscle relaxant activity at higher concentrations. Ruta graveolens extract also significantly decreased the number of squares visited by rats in open field apparatus at all tested concentrations (3.5-20%w/v). However, the significant decrease in number of rearings was only noticed at concentrations of (15 and 20%w/v). The results indicate that Ruta graveolens contains compound(s) capable to inhibit convulsions, decrease SMA and/or diminish skeletal muscle tone in animal models. This data and the previously generated data together point to a general depression trend of CNS produced by Ruta graveolens.Keywords: Ruta graveolens, open field, skeletal muscle relaxation
Procedia PDF Downloads 418524 Study of the Composition of Lipids in Different Kinds of Packaged Food Products
Authors: Zineb Taidirt, Fathia Sebahi, Mohamed Karim Guarchani, Anissa Berkane, Noureddine Smail, Ouahiba Hadjoudj
Abstract:
Cardiovascular diseases are one of the most important causes of death in Algeria. Several risk factors are responsible for this, including the consumption of foods containing saturated fat and trans fatty acids TFAs. This brief presents the results of a descriptive study of the lipid composition of 251 food products marketed in Algeria. The objective of the study is to describe the nature and composition of lipids and to verify the compliance of saturated and trans fatty acids intakes with the regulations. The study is based on data from the nutrition labelling of marketed food products. The results showed that the lipids in foodstuffs are diverse in nature and of varying amounts, but their nature is not specified on all products. In addition, the required content of saturated fatty acids is mentioned only in 29.48% of the products; 21.62% of them do not comply with the standard. Hydrogenation of fats, which produced Trans fatty acids, is common: 19.92% of products contain hydrogenated fats, and 74.89% may contain them according to the aspect of the lipid (solid fat). However, the trans fatty acid content is only mentioned in 5.18% of the products. The latter is above the limits set by Algerian regulations in 50% of the butter samples studied. The composition of lipids in mono- and polyunsaturated fatty acids essential for the body is insufficient: only 13.94% of the products inform their contents on their labels. It is necessary to adopt mandatory restriction of trans fatty acids, to ban the use of partially-hydrogenated oils, and to require required mandatory labeling of the TFAs and the other fatty acids on packaged foods, and to conduct more studies in order to appreciate the intake of TFAs and saturated fat and appreciate their effects on the Algerian population and to get more informed about the composition of the lipid in packaged foods.Keywords: cardiovascular diseases, lipids, nutrition labelling, lipids, trans fatty acids
Procedia PDF Downloads 127523 The Factors Associated with Health Status among Community Health Volunteers in Thailand
Authors: Lapatrada Numkham, Saowaluk Khakhong, Jeeraporn Kummabutr
Abstract:
Non-communicable diseases (NCDs) are the leading cause of death in worldwide. Thailand also concerns and focuses on reduction a new case of these diseases. Community Health Volunteers (CHV) is important health personnel in primary health care and performs as a health leader in the community. If the health of CHV changes, it would impact on the performance to promote health of families and community. This cross-sectional study aimed to 1) describe the health status of community health volunteers and 2) examine the factors associated with health status among community health volunteers. The sample included 360 community health volunteers in a province in central Thailand during September-December 2014. Data were collected using questionnaires on health information, knowledge of health behaviors, and health behaviors. Body weight, height, waist circumference (WC), blood pressure (BP), and blood glucose (BS) (fingertip) were assessed. Data were analyzed using descriptive statistics and chi-square test. There were three hundred and sixty participants with 82.5% being women. The mean age was 54 + 8.9 years. Forty-seven percent of the participants had co-morbidities. Hypertension was the most common co-morbidity (26.7%). The results revealed that the health status of the volunteers included: no underlying disease, having risk of hypertension (HT) & diabetes mellitus (DM), and having HT&DM at 38.3%, 30.0%, and 31.7% respectively. The chi-square test revealed that the factors associated with health status among the volunteers were gender, age, WC and body mass index (BMI). The results suggested that community health nurses should; 1) implement interventions to decrease waist circumference and lose weight through education programs, especially females; 2) monitor people that have a risk of HT&DM and that have HT&DM by meeting and recording BP level, BS level, WC and BMI; and 3) collaborate with a district public health officer to initiate a campaign to raise awareness of the risks of chronic diseases among community health volunteers.Keywords: community health volunteers, health status, risk of non-communicable disease, Thailand
Procedia PDF Downloads 359522 Non Enzymatic Electrochemical Sensing of Glucose Using Manganese Doped Nickel Oxide Nanoparticles Decorated Carbon Nanotubes
Authors: Anju Joshi, C. N. Tharamani
Abstract:
Diabetes is one of the leading cause of death at present and remains an important concern as the prevalence of the disease is increasing at an alarming rate. Therefore, it is crucial to diagnose the accurate levels of glucose for developing an efficient therapeutic for diabetes. Due to the availability of convenient and compact self-testing, continuous monitoring of glucose is feasible nowadays. Enzyme based electrochemical sensing of glucose is quite popular because of its high selectivity but suffers from drawbacks like complicated purification and immobilization procedures, denaturation, high cost, and low sensitivity due to indirect electron transfer. Hence, designing a robust enzyme free platform using transition metal oxides remains crucial for the efficient and sensitive determination of glucose. In the present work, manganese doped nickel oxide nanoparticles (Mn-NiO) has been synthesized onto the surface of multiwalled carbon nanotubes using a simple microwave assisted approach for non-enzymatic electrochemical sensing of glucose. The morphology and structure of the synthesized nanostructures were characterized using scanning electron microscopy (SEM) and X-Ray diffraction (XRD). We demonstrate that the synthesized nanostructures show enormous potential for electrocatalytic oxidation of glucose with high sensitivity and selectivity. Cyclic voltammetry and square wave voltammetry studies suggest superior sensitivity and selectivity of Mn-NiO decorated carbon nanotubes towards the non-enzymatic determination of glucose. A linear response between the peak current and the concentration of glucose has been found to be in the concentration range of 0.01 μM- 10000 μM which suggests the potential efficacy of Mn-NiO decorated carbon nanotubes for sensitive determination of glucose.Keywords: diabetes, glucose, Mn-NiO decorated carbon nanotubes, non-enzymatic
Procedia PDF Downloads 235521 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer
Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam
Abstract:
Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations
Procedia PDF Downloads 131520 Development of Electronic Services in Georgia: Analysis of Current Situation
Authors: Dato Surmanidze, Dato Antadze, Tornike Partenadze
Abstract:
Public online services in Georgia are concentrated on main target segments: public administration, business, population, non-governmental and other interested organizations. Therefore, the strategy of digital Georgia is focused on providing G2C, G2B/B2G, G2NGO and G2G services. In G2C framework sophisticated and high-technological online services have been developed in order to provide passports, identity cards, documentations concerning residence and civil acts (birth, marriage, divorce, child adoption, change of name and surname, death, etc) as well as other services. Websites like my.gov.ge and sda.gov.ge have distance services like electronic application, processing and decision making. In line with international standards automatic services like electronic tenders, product catalogues, invoices and payment have been developed. This creates better investment climate for foreign companies in Georgia in the framework of G2B politics. The website mybusiness.gov.ge creates better conditions for local business. Among electronic services is e-NRMS (electronic system for national resource management) which was introduced by the Ministry of Finance of Georgia. The system was created in order to ensure management of national resources by state and business organizations. It is integrated with bank services and provides G2C, G2B and B2G representatives with electronic services. Also a portal meteo.gov.ge was created which gives electronic services concerning air, geological, environmental and pollution issues. Also worknet.gov.ge should be mentioned which is an electronic hub of information management for employers and employees. The information portal of labor market will facilitate receipt of information, its analysis and delivery to interested people like employers and employees. However, nowadays it’s been two years that only employees portal is activated. Therefore, awareness about the portal, its competitiveness and success is undermined.Keywords: electronic services, public administration, information technology, information society
Procedia PDF Downloads 268519 Protective Effect of Rosemary Extract against Toxicity Induced by Egyptian Naja haje Venom
Authors: Walaa H. Salama, Azza M. Abdel-Aty, Afaf S. Fahmy
Abstract:
Background: Egyptian Cobra; Naja haje (Elapidae) is one of most common snakes, widely distributed in Egypt and its envenomation causes multi-organ failure leading to rapid death. Thus, Different medicinal plants showed a protective effect against venom toxicity and may complement the conventional antivenom therapy. Aim: The present study was designed to assess both the antioxidant capacity of methanolic extract of rosemary leaves and evaluate the neutralizing ability of the extract against hepatotoxicity induced by Naja haje venom. Methods: The total phenolic and flavonoid contents and the antioxidant capacity of the methanolic rosemary extract were estimated by DPPH and ABTS Scavenging methods. In addition, the rosemary extract were assessed for anti-venom properties under in vitro and in vivo standard assays. Results: The rosemary extract had high total phenolic and flavonoid content as 12 ± 2 g of gallic acid equivalent per 100 gram of dry weight (g GAE/100g dw) and 5.5 ± 0.8 g of catechin equivalent per 100 grams of dry weight (g CE/100g dw), respectively. In addition, the rosemary extract showed high antioxidant capacity. Furthermore, The rosemary extract were inhibited in vitro the enzymatic activities of phospholipase A₂, L-amino acid oxidase, and hyaluronidase of the venom in a dose-dependent manner. Moreover, indirect hemolytic activity, hepatotoxicity induced by venom were completely neutralized as shown by histological studies. Conclusion: The phenolic compounds of rosemary extract with potential antioxidant activity may be considered as a promising candidate for future therapeutics in snakebite therapy.Keywords: antioxidant activity, neutralization, phospholipase A₂ enzyme, snake venom
Procedia PDF Downloads 182518 Spatiotemporal Modeling of Under-Five Mortality and Associated Risk Factors in Ethiopia
Authors: Melkamu A. Zeru, Aweke A. Mitiku, Endashaw Amuka
Abstract:
Background: Under-five mortality is the likelihood that a baby will pass away before turning exactly 5 years old, represented as a percentage per 1,000 live births. Exploring the spatial distribution and identifying the temporal pattern is important to reducing under-five child mortality globally, including in Ethiopia. Thus, this study aimed to identify the risk factors of under-five mortality and the spatiotemporal variation in Ethiopian administrative zones. Method: This study used the 2000-2016 Ethiopian Demographic and Health Survey (EDHS) data, which were collected using a two-stage sampling method. A total of 43,029 (10,873 in 2000, 9,861 in 2005, 11,654 in 2011, and 10,641 in 2016) weighted sample under-five child mortality was used. The space-time dynamic model was employed to account for spatial and time effects in 65 administrative zones in Ethiopia. Results: From the result of a general nesting spatial-temporal dynamic model, there was a significant space-time interaction effect [γ = -0.1444, 95 % CI (-0.6680, -0.1355)] for under-five mortality. The increase in the percentages of mothers illiteracy [𝛽 = 0.4501, 95% CI (0.2442, 0.6559)], not vaccinated[𝛽= 0.7681, 95% CI (0.5683, 0.9678)], unimproved water[𝛽= 0.5801, CI (0.3793, 0.7808)] were increased death rates for under five children while increased percentage of contraceptive use [𝛽= -0.6609, 95% CI (-0.8636, -0.4582)] and ANC visit > 4 times [𝛽= -0.1585, 95% CI(-0.1812, -0.1357)] were contributed to the decreased under-five mortality rate at the zone in Ethiopia. Conclusions: Even though the mortality rate for children under five has decreased over time, still there is still higher in different zones of Ethiopia. There exists spatial and temporal variation in under-five mortality among zones. Therefore, it is very important to consider spatial neighbourhoods and temporal context when aiming to avoid under-five mortality.Keywords: under-five children mortality, space-time dynamic, spatiotemporal, Ethiopia
Procedia PDF Downloads 37517 Infused Mesenchymal Stem Cells Ameliorate Organs Morphology in Cerebral Malaria Infection
Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das
Abstract:
Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death
Procedia PDF Downloads 103516 Sonodynamic Activity of Porphyrins-SWCNT
Authors: F. Bosca, F. Foglietta, F. Turci, E. Calcio Gaudino, S. Mana, F. Dosio, R. Canaparo, L. Serpe, A. Barge
Abstract:
In recent years, medical science has improved chemotherapy, radiation therapy and adjuvant therapy and has developed newer targeted therapies as well as refining surgical techniques for removing cancer. However, the chances of surviving the disease depend greatly on the type and location of the cancer and the extent of the disease at the start of treatment. Moreover, mainstream forms of cancer treatment have side effects which range from the unpleasant to the fatal. Therefore, the continuation of progress in anti-cancer therapy may depend on placing emphasis on other existing but less thoroughly investigated therapeutic approaches such as Sonodynamic Therapy (SDT). SDT is based on the local activation of a so called 'sonosensitizer', a molecule able to be excited by ultrasound, the radical production as a consequence of its relaxation processes and cell death due to different mechanisms induced by radical production. The present work deals with synthesis, characterization and preliminary in vitro test of Single Walled Carbon Nanotubes (SWCNT) decorated with porphyrins and biological vectors. The SWCNT’s surface was modified exploiting 1, 3-dipolar cycloaddition or Dies Alder reactions. For this purpose, different porphyrins scaffolds were ad-hoc synthesized using also non-conventional techniques. To increase cellular specificity of porphyrin-conjugated SWCNTs and to improve their ability to be suspended in aqueous solution, the modified nano-tubes were grafted with suitable glutamine or hyaluronic acid derivatives. These nano-sized sonosensitizers were characterized by several methodologies and tested in vitro on different cancer cell lines.Keywords: sonodynamic therapy, porphyrins synthesis and modification, SWNCT grafting, hyaluronic acid, anti-cancer treatment
Procedia PDF Downloads 390515 Obesity and Physical Inactivity: Contributing Factors to Hypertension in Early Adults
Authors: Sadaf Ambreen, Ayesha Bibi, Sara Rafiq
Abstract:
Hypertension is a medical condition in which blood pressure in the arteries is elevated than the normal, having systolic blood pressure more than 120mmHg and diastolic blood pressure more than 80 mmHg. It leads to health complications and increase the risk of diseases such as stroke, heart failure, heart attack, and even death. The aim of the current study was to evaluate nutritional status and activity level among hypertensive early adults in District Mardan Data was collected from the subjects of Public Hospital, Mardan Medical Complex, through questionnaire. A complete information about individual sociodemographic, anthropometry and health status were collected, and physical activity was assessed by using IPAQ questionnaire. A total of 150 individuals were included in the study, in which 90% were females, and 10% were males. Data was analyzed through SPSS Version 22. Majority of the study subjects, 88%, were married, 70% having nuclear living system, 43% were having elementary education, and 43% were working as laborer. Body mass index and waist circumference in female counterpart were found to be positively associated with hypertension and was found statistically significant P=<0.01. Results showed that majority of females were fall in hypertension crisis category with mild activity, and males were having hypertension stage 1 with moderate activity. Our study concluded that non-optimal nutritional status and physical inactivity resulted in elevated blood pressure in females, therefore, lifestyle change such as optimal nutritional status and physical activity may play key role in reducing risk of hypertension.Keywords: obesity/overwight, body mass index, waist circumference, early adulthood
Procedia PDF Downloads 148514 Awareness on Risk Factors of Cardiovascular Disease among Patients with Diabetes Mellitus Attending Diabetic Clinic of B. P. Koirala Institute of Health Sciences
Authors: Ram Sharan Mehta, Dina Khanal, Pushpa Parajuli, Gayanand Mandal, Bijaya Bartuala
Abstract:
Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Adequate awareness of risk factors of CVD is the first step towards effective preventive strategies to combat the CVD burden in diabetes patients.This study aims to assess the awareness on risk factors of CVD among patients with diabetes mellitus attending diabetic clinic of BPKIHS and to find the association between awareness with their selected socio demographic variables. Methods and Material: A descriptive cross sectional study was conducted among 112 patients with diabetes in diabetic clinic of BPKIHS. Convenient sampling technique was used for data collection over duration of one month using interview schedule by HDFQ II tool. Data were analyzed by using descriptive and inferential statistics. (Chi square). Results: The mean age of respondents was 55.4±12.13 years. That mean HDFQ score was 14.31± 5.08. Only 33% of the respondents had adequate level of awareness whereas majority of the respondents (67%) had inadequate level of awareness. Majority of the respondent (83.9%) were aware about smoking, (78.6%) physical activity, (75%) increasing age, (75.9%) high blood pressure, (71.4%) overweight respectively. Whereas most of the respondents were not aware of high cholesterol, fatty diet, preventive strategies and association of diabetes with CVD. Awareness was statistically significant with (p=0.043) educational status, (p=0.025) monthly income, (p=0.05) residence, (p=0.006) CVD information received and (p=0.022) co morbid condition as a heart disease. Conclusion: The findings of this study concluded most of the respondents had an inadequate level of awareness on risk factors of CVD. So Effective education and appropriate preventive strategies of CVD are indeed important to reduce CVD burden in diabetes patients.Keywords: cardiovascular disease, awareness, diabetes patients, risk
Procedia PDF Downloads 135513 Effect of Fire Retardant Painting Product on Smoke Optical Density of Burning Natural Wood Samples
Authors: Abdullah N. Olimat, Ahmad S. Awad, Faisal M. AL-Ghathian
Abstract:
Natural wood is used in many applications in Jordan such as furniture, partitions constructions, and cupboards. Experimental work for smoke produced by the combustion of certain wood samples was studied. Smoke generated from burning of natural wood, is considered as a major cause of death in furniture fires. The critical parameter for life safety in fires is the available time for escape, so the visual obscuration due to smoke release during fire is taken into consideration. The effect of smoke, produced by burning of wood, depends on the amount of smoke released in case of fire. The amount of smoke production, apparently, affects the time available for the occupants to escape. To achieve the protection of life of building occupants during fire growth, fire retardant painting products are tested. The tested samples of natural wood include Beech, Ash, Beech Pine, and white Beech Pine. A smoke density chamber manufactured by fire testing technology has been used to perform measurement of smoke properties. The procedure of test was carried out according to the ISO-5659. A nonflammable vertical radiant heat flux of 25 kW/m2 is exposed to the wood samples in a horizontal orientation. The main objective of the current study is to carry out the experimental tests for samples of natural woods to evaluate the capability to escape in case of fire and the fire safety requirements. Specific optical density, transmittance, thermal conductivity, and mass loss are main measured parameters. Also, comparisons between samples with paint and with no paint are carried out between the selected samples of woods.Keywords: extinction coefficient, optical density, transmittance, visibility
Procedia PDF Downloads 237512 A Two Arm Double Parallel Randomized Controlled Trail of the Effects of Health Education Intervention on Insecticide Treated Nets Use and Its Practices among Pregnant Women Attending Antenatal Clinic: Study Protocol
Authors: Opara Monica, Suriani Ismail, Ahmad Iqmer Nashriq Mohd Nazan
Abstract:
The true magnitude of the mortality and morbidity attributable to malaria worldwide is, at best, a scientific guess, although it is not disputable that the greatest burden is in sub-Saharan Africa. Those at highest risk are children younger than 5 years and pregnant women, particularly primigravidae. Nationally, malaria remains the third leading cause of death and is still considered a major public health problem. Therefore, this study is aimed to assess the effectiveness of health education intervention on insecticide-treated net use and its practices among pregnant women attending antenatal clinics. Materials and Methods: This study will be an intervention study with two arms double parallel randomized controlled trial (blinded) to be conducted in 3 stages. The first stage will develop health belief model (HBM) program, while in the second stage, pregnant women will be recruited, assessed (baseline data), randomized into two arms of the study, and follow-up for six months. The third stage will evaluate the impact of the intervention on HBM and disseminate the findings. Data will be collected with the use of a structured questionnaire which will contain validated tools. The main outcome measurement will be the treatment effect using HBM, while data will be analysed using SPSS, version 22. Discussion: The study will contribute to the existing knowledge on hospital-based care programs for pregnant women in developing countries where the literature is scanty. It will generally give insight into the importance of HBM measurement in interventional studies on malaria and other related infectious diseases in this setting.Keywords: malaria, health education, insecticide-treated nets, sub-Saharan Africa
Procedia PDF Downloads 123511 Artificial Intelligence Based Online Monitoring System for Cardiac Patient
Authors: Syed Qasim Gilani, Muhammad Umair, Muhammad Noman, Syed Bilawal Shah, Aqib Abbasi, Muhammad Waheed
Abstract:
Cardiovascular Diseases(CVD's) are the major cause of death in the world. The main reason for these deaths is the unavailability of first aid for heart failure. In many cases, patients die before reaching the hospital. We in this paper are presenting innovative online health service for Cardiac Patients. The proposed online health system has two ends. Users through device developed by us can communicate with their doctor through a mobile application. This interface provides them with first aid.Also by using this service, they have an easy interface with their doctors for attaining medical advice. According to the proposed system, we developed a device called Cardiac Care. Cardiac Care is a portable device which a patient can use at their home for monitoring heart condition. When a patient checks his/her heart condition, Electrocardiogram (ECG), Blood Pressure(BP), Temperature are sent to the central database. The severity of patients condition is checked using Artificial Intelligence Algorithm at the database. If the patient is suffering from the minor problem, our algorithm will suggest a prescription for patients. But if patient's condition is severe, patients record is sent to doctor through the mobile Android application. Doctor after reviewing patients condition suggests next step. If a doctor identifies the patient condition as critical, then the message is sent to the central database for sending an ambulance for the patient. Ambulance starts moving towards patient for bringing him/her to hospital. We have implemented this model at prototype level. This model will be life-saving for millions of people around the globe. According to this proposed model patients will be in contact with their doctors all the time.Keywords: cardiovascular disease, classification, electrocardiogram, blood pressure
Procedia PDF Downloads 184510 Discussion on the Impact Issues in Urban by Earthquake Disaster Cases
Authors: M. C. Teng, M. C. Ke, C. Y. Yang, S. S. Ke
Abstract:
There are more than one thousand times a year of felt earthquakes in Taiwan. Because earthquakes are disaster threats to urban infrastructure, they often disrupt infrastructure services. For example, the highway system is very important to transportation infrastructure; however, it is vulnerable to earthquakes and typhoons in Taiwan. When a highway system is damaged by disaster, it will create a major impact on post-disaster communications and emergency relief and affect disaster relief works. In a study case on September 18th, 2022, the Taitung Chihshang earthquake, with a magnitude of 6.8 on the Richter scale with a depth of 7 km, caused one death; 171 people were injured and had a significant urban infrastructure impact. Hualien and Taitung areas have a large number of surface ruptures, road disruptions due to the collapses, over ten cases of bridges failure or closed, partial railroad section service shutdown, building collapses, and casualties. Taitung Chihshang earthquake, the peak ground acceleration is 585 gal (cm/s²), and the seismic intensity is Level 6 Upper(6+)in Chishang, Taitung County. After the earthquakes, we conducted on-site disaster investigation works in the disaster area; the disaster investigation works included a public and private building survey, a transportation facility survey, a total of ten damaged bridges, and one railroad station damaged were investigated in this investigation. The results showed that the affected locations were mainly concentrated along the Chihshang fault and the Yuli fault in the Huatung Longitudinal Valley. We recorded and described the impact and assessed its influence region in terms of its susceptibility to and the consequences of earthquake attacks. In addition, a lesson is learned from this study regarding the key issues after the Taitung Chihshang earthquake.Keywords: earthquake, infrastructure, disaster investigation, lesson learned
Procedia PDF Downloads 62509 Neuroprotective Effect of Crocus sativus against Cerebral Ischemia in Rats
Authors: Rehab F. Abdel-Rahman, Sally A. El Awdan, Rehab R. Hegazy, Dina F. Mansour, Hanan A. Ogaly, Marwan Abdelbaset
Abstract:
Disorders of the cerebral circulation are the leading cause of numerous neurological and psychiatric illnesses. The transient middle cerebral artery occlusion model (MCAO) is considered to be a reliable and reproducible rodent model of cerebral ischemia. The purpose of the current study was to examine the neuroprotective effects of Crocus sativus (saffron) in a rat model of left middle cerebral artery MCAO. Male Wistar rats were anesthetized and subjected to 1 h of MCAO followed by 48 h reperfusion or sham surgery. One group of the ischemia operated animals was kept as left brain ischemia/reperfusion (I/R). Another 2 operated groups received saffron extract (100 or 200 mg/kg, i.p) four times (60 min before the surgery, during the surgery, and on days 1 and 2 after the occlusion). During the experiment, behavioral tests were performed. After 72 h the animals were euthanized and their left brain hemispheres were used in the biochemical, histopathological, and immunohistochemical studies. Saffron administration revealed an improvement in I/R-induced alteration of locomotor balance and coordination ability of rats. Moreover, saffron decreased the brain content of malondialdehyde, nitric oxide, brain natriuretic peptide and vascular endothelial growth factor with significant increase of reduced glutathione. Immunohistochemical evaluation of caspase-3 and Bax protein expression revealed reduction in I/R-enhanced apoptosis in saffron treated rats. In conclusion, saffron treatment decreases ischemic brain injury in association with inhibition of apoptotic and oxidative cell death in a dose dependent manner.Keywords: caspase-3, cerebral ischemia, Crocus sativus, rats, vascular endothelial growth factor
Procedia PDF Downloads 258508 Potentials and Challenges of Adventure Tourism Development: A Case Study of Kashmir Valley, India
Authors: Abdul Hamid Mir
Abstract:
Tourism which is considered as the economic bonanza of Jammu and Kashmir plays an important role in the socio-economic development of Jammu and Kashmir. It is considered as a multi-segmented industry which provides different type of jobs like hotel managers, receptionists, guides, tour operators, travel agents, photographers, etc. Kashmir Valley which is one of the three meso regions (Jammu, Kashmir and Ladakh) of Jammu and Kashmir State is famous all over the world due to its natural beauty. It attracts tourists from the every corner of the globe that is why it has earned name as ‘Paradise on Earth’ and ‘Switzerland of Asia’. It is full of natural treasure and gratifies the several types of tourists. The tourists are experiences fun, thrilling events and safe experience in Kashmir valley, but on the other hand, the adventure tourists are experiencing the physical risks, dangers and losses (injuries, death etc) too. Kashmir valley has greater potential to become one of the best adventure tourism destinations in the world. It offers immense opportunities to the adventurists to explore the wonderful exotic Himalayan ranges and landscapes, in addition, to facing the challenges of fast flowing rivers. Adventure tourism is at the initial stage of development in Kashmir valley and virgin areas needs to be explored and develop which in result will increase not only tourist arrivals but also enhance the business opportunities and economy of local people in Kashmir. Thus the exploitation of virginity of adventure tourism potentials in Kashmir valley is need of the hour. Therefore the present study highlights the potentials of adventure tourism in Kashmir valley and also focuses on the problems in the development of adventure tourism. Furthermore, the study extends to give various recommendations and suggestions in order to develop adventure tourism and broaden the base of tourist arrivals on one hand and sustained the growth on the other hand.Keywords: adventure, Kashmir, tourism, tourists, potential, rafting, skiing
Procedia PDF Downloads 245507 Emergency Management and Patient Transportation of Road Traffic Accident Victims Admitted to the District General Hospital, Matale, Sri Lanka
Authors: Asanka U. K. Godamunne
Abstract:
Road traffic accidents (RTA) are a leading cause of death globally as well as in Sri Lanka and results in a large proportion of disability especially among young people. Ninety-percent of world’s road traffic deaths occur in low- and middle-income countries. The gross disparities in injury outcomes relate to immediate post-crash and hospital management. Emergency management, methods of patient transportation following road traffic accidents and safety measures are important factors to reduce mortality and morbidity. Studies in this area are limited in Sri Lanka. The main objective of this research was to assess the emergency management and proper method of transportation of road traffic accident victims. This offers the best way to explore the ways to reduce the mortality and morbidity and raise the public awareness. This study was conducted as a descriptive cross-sectional study. All the consecutive road traffic accident victims admitted to surgical wards at District General Hospital, Matale, Sri Lanka, over a period of three months were included in the study. Data from 387 victims were analyzed. The majority were in the 20-30 year age group. Seventy six percent of the patients were males. Motorcycles and trishaws were most affected. First-aid was given to only 2% of patients and it was given by non-medical persons. A significant proportion of patients (75%) were transported to the hospital by trishaws and only 1% transported by ambulance. About 86% of the patients were seated while transport and 14% were flat. Limbs and head were the most affected areas of the body. As per this study, immediate post-crash management and patient transportation were not satisfactory. There is a need to strengthen certain road safety laws and make sure people follow them.Keywords: emergency management, patient transportation, road traffic accident victims, Sri Lanka
Procedia PDF Downloads 245506 The Influence of Amygdalin on Glioblastoma Multiforme Cell Lines
Authors: Sylwia K. Naliwajko, Justyna Moskwa, Patryk Nowakowski, Renata Markiewicz-Zukowska, Krystyna Gromkowska-Kepka, Anna Puscion-Jakubik, Maria H. Borawska
Abstract:
Amygdalin is found in many fruit seeds, including apricot, peach, quince, apples, and almonds. Amygdalin (also named vitamin B17), as well as its sources, are commonly used as an alternative therapy or prevention of cancer. The potential activity of amygdalin is related to its enzymatic degradation to the hydrogen cyanide. Hydrogen cyanide is a toxic substance that causes liver and nerves damage, fever, coma or even death. Amygdalin is much better tolerated after intravenous than oral administration. The aim of this study was to examine the influence of amygdalin on glioblastoma multiforme cell lines. Three glioblastoma multiforme cell lines – U87MG, T98, LN18 were incubated (48 h) with amygdalin in concentrations 100, 250, 500, 1000 and 2000 µg/mL. The MTT (Thiazolyl Blue Tetrazolium Bromide) test and DNA binding test by [3H]-thymidine incorporation were used to determine the anti-proliferative activity of amygdalin. The secretion of metalloproteinases (MMP2 and MMP-9) from U87MG cells was estimated by gelatin zymography. The statistical analysis was performed using Statistica v. 13.0 software. The data was presented as a % of control. Amygdalin did not show significant inhibition of viability of all the glioblastoma cells in concentrations 100, 250, 500, 1000 µg/mL. In 2000 µg/mL there were significant differences compared to the control, but inhibition of viability was less than 20% (more than 80% of control). The average viability of U87MG cells was 92,0±4%, T98G: 85,8±3% and LN18: 94,7±2% of the control. There was no dose-response viability, and IC50 value was not recognized. DNA binding in U87MG cells was not inhibited (109,0±3 % of control). After treatment with amygdalin, we observed significantly increased secretion of MMP2 and MMP9 in U87MG cells (130,3±14% and 112,0±5% of control, respectively). Our results suggest that amygdalin has no anticancer activity in glioblastoma cell lines.Keywords: amygdalin, anticancer, cell line, glioblastoma
Procedia PDF Downloads 216505 Type 2 Diabetes Mellitus Among a St. Lucian Population: What We Know about Lifestyle Modification
Authors: Bradley Fevrier
Abstract:
Background: Type 2 diabetes mellitus, a non-communicable metabolic disorder, is a fast-growing problem for health, as it presents numerous complications and death worldwide. St. Lucia, much like most other emerging nation in the Caribbean, struggles with the management of type 2 diabetes mellitus (T2DM) among its populace. Good knowledge, attitude, and practices [KAP] of T2DM are essential in the prevention and management of this disease.Lifestyle adaptation, including increased knowledge, positive attitude, and efficient practice towards lifestyle modifications, can avert the advancement of difficulties associated with diabetes. Methods: An institutional-based cross-sectional study was conducted during the period June 15, 2022, to July15 2022. Data were collected by using the self-administered questionnaire designed to collect the required information from participants, and the data wasanalyzed using the statistical package for social science (SPSS) version 26. Knowledge, attitude, and practice of lifestyle modification among participants were determined using descriptive statistics. Results: A total of 402 participants completed the study, fully yielding an 84% response rate. Overall, the assessed levels of KAP relating to the life-threatening complications of T2DM were moderate. Results further indicated that women outnumbered men 68.4% to 31.6%, respectively. Significant positive correlation (r= 0.244, p<0.001) and (r=.203, p<0.001) were found between the knowledge level as well as the attitude level of study respondents. Conclusion: The overall study findings regarding the level of knowledge and attitude concerning lifestyle modifications among study participants were interpreted as generally high. However, the practice of healthy lifestyle modification habits was poor. The current findings suggest a need for structured educational campaigns prioritizing the importance of lifestyle modifications (weight loss, smoking cessation, physical exercise) to the general population.Keywords: Diabetes, knowledge, lifestyle, survey
Procedia PDF Downloads 127504 Effects of Seed Culture and Attached Growth System on the Performance of Anammox Hybrid Reactor (AHR) Treating Nitrogenous Wastewater
Authors: Swati Tomar, Sunil Kumar Gupta
Abstract:
The start-up of anammox (anaerobic ammonium oxidation) process in hybrid reactor delineated four distinct phases i.e. cell lysis, lag phase, activity elevation and stationary phase. Cell lysis phase was marked by death and decay of heterotrophic denitrifiers resulting in breakdown of organic nitrogen into ammonium. Lag phase showed initiation of anammox activity with turnover of heterotrophic denitrifiers, which is evident from appearance of NO3-N in the effluent. In activity elevation phase, anammox became the dominant reaction, which can be attributed to consequent reduction of NH4-N into N2 with increased NO3-N in the effluent. Proper selection of mixed seed culture at influent NO2-/NH4+ ratio (1:1) and hydraulic retention time (HRT) of 1 day led to early startup of anammox within 70 days. Pseudo steady state removal efficiencies of NH4+ and NO2- were found as 94.3% and 96.4% respectively, at nitrogen loading rate (NLR) of 0.35 kg N/m3d at an HRT of 1 day. Analysis of the data indicated that attached growth system contributes an additional 11% increase in the ammonium removal and results in an average of 29% reduction in sludge washout rate. Mass balance study of nitrogen indicated that 74.1% of total input nitrogen is converted into N2 gas followed by 11.2% being utilized in biomass development. Scanning electron microscope (SEM) observation of the granular sludge clearly showed the presence of cocci and rod shaped microorganisms intermingled on the external surface of the granules. The average size of anammox granules (1.2-1.5 mm) with an average settling velocity of 45.6 m/h indicated a high degree of granulation resulting into formation of well compacted granules in the anammox process.Keywords: anammox, hybrid reactor, startup, granulation, nitrogen removal, mixed seed culture
Procedia PDF Downloads 184503 The Prediction Mechanism of M. cajuputi Extract from Lampung-Indonesia, as an Anti-Inflammatory Agent for COVID-19 by NFκβ Pathway
Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih
Abstract:
Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi
Procedia PDF Downloads 87502 Assessment of Vehicular Accidents and Possible Mitigation Measures: A Case of Ahmedabad, Gujarat, India
Abstract:
Rapid urbanization is one of the consequences of rapid population explosion, which has also led to massive increase in number of motorized vehicles essential for carrying out all activities needed for sustaining urban livelihood. With this increased use of motorized vehicles over the time there has also been an increase in number of accidents. Study of road network and geometric features are essential to tackle problems of road accidents in any district or town. The increase in road accidents is one of the burning issues in the present society. Records show that there is one death at every 3.7 minutes because of road accident. It has been found from the research that, accidents occur due to, mistakes of the driver (86%) followed by bad street condition (5%), mistake of pedestrian (4%), as well as technical and maintenance defects (1%). Here, case study of Ahmedabad, Gujarat is taken up where first road safety level is assessed considering various parameters. The study confined to accident characteristics of all types of vehicles. For deeper analysis, road safety index for various stretches in Ahmedabad was found out. Crash rate for same stretches was found out. Based on various parameters priority was decided so that which stretch should be look out first to minimize road accidents on that stretch and which stretch should look out last. The major findings of the study are that accident severity of Ahmedabad has increased, but accident fatality risk has decreased; thus there is need to undertake some traffic engineering measures or make some traffic rules that are strictly followed by traffic. From the above study and literature studied it is found that Ahmedabad is suffering from similar problem of accidents and injuries and deaths caused by them, after properly investigating the issue short-term and long-term solutions to minimize road accidents have been presented in this paper.Keywords: accident severity index, accident fatality rate, accident fatality risk, accident risk, road safety index
Procedia PDF Downloads 142501 Association Between Short-term NOx Exposure and Asthma Exacerbations in East London: A Time Series Regression Model
Authors: Hajar Hajmohammadi, Paul Pfeffer, Anna De Simoni, Jim Cole, Chris Griffiths, Sally Hull, Benjamin Heydecker
Abstract:
Background: There is strong interest in the relationship between short-term air pollution exposure and human health. Most studies in this field focus on serious health effects such as death or hospital admission, but air pollution exposure affects many people with less severe impacts, such as exacerbations of respiratory conditions. A lack of quantitative analysis and inconsistent findings suggest improved methodology is needed to understand these effectsmore fully. Method: We developed a time series regression model to quantify the relationship between daily NOₓ concentration and Asthma exacerbations requiring oral steroids from primary care settings. Explanatory variables include daily NOₓ concentration measurements extracted from 8 available background and roadside monitoring stations in east London and daily ambient temperature extracted for London City Airport, located in east London. Lags of NOx concentrations up to 21 days (3 weeks) were used in the model. The dependent variable was the daily number of oral steroid courses prescribed for GP registered patients with asthma in east London. A mixed distribution model was then fitted to the significant lags of the regression model. Result: Results of the time series modelling showed a significant relationship between NOₓconcentrations on each day and the number of oral steroid courses prescribed in the following three weeks. In addition, the model using only roadside stations performs better than the model with a mixture of roadside and background stations.Keywords: air pollution, time series modeling, public health, road transport
Procedia PDF Downloads 142500 Understanding Inhibitory Mechanism of the Selective Inhibitors of Cdk5/p25 Complex by Molecular Modeling Studies
Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee
Abstract:
Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25
Procedia PDF Downloads 139499 Ventriculo-Gallbladder Shunt: Case Series and Literature Review
Authors: Sandrieli Afornali, Adriano Keijiro Maeda, Renato Fedatto Beraldo, Carlos Alberto Mattozo, Ricardo Nascimento Brito
Abstract:
BACKGROUND: The most used variety in hydrocephalus treatment is the ventriculoperitoneal shunt (VPS). However, it may fails in 20 to 70% of cases. It makes necessary to have alternative cavities for the implantation of the distal catheter. Ventriculo-atrial shunting (VAS) is described as the second option. To our knowledge, there are 121 reported cases of VGB shunt in children until 2020 and a highly variable success rate, from 25 to 100%, with an average of 63% of patients presenting good long-term results. Our goal is to evaluate the epidemiological profile of patients submitted to ventriculo-gallbladder (VGB) shunt and, through a review of literature, to compare our results with others series. METHODS: a retrospective cross-sectional observational study of a case series of nine patients. The medical records of all patients were reviewed, who underwent VGB shunt at the Hospital Pequeno Príncipe from Curitiba, Paraná, Brazil, from January 2014 to October 2022. The inclusion criteria were: patients under 17 years of age with hydrocephalus of any etiology, currently using or prior to VGB shunt. RESULTS: There were 6 (66,7%) male and 3 (33,3%) female. The average age of 73.6 months or 6.1 years at the time of surgery. They were submitted on average 5.1 VPS reviews previous to VGB shunt. Five (55,5%) had complications of VGB shunt: infection (11.1%), atony (11.1%), hypodrainage due to kinking the distal catheter in the solution (11.1%) and ventriculoenteric fistula (22.2%); all these patients were cured at surgical reapproach, and in 2 of them the VGB shunt was reimplanted. Two patients died (22.2%), and five (55,5%) patients maintained the use of VGB shunt in the follow-up period; and in 4 (44.4%) there was never need for review. CONCLUSION: VGB shunt tends to be underestimated because it is still unconventional and little publicized in literature. Our article shows a lower risk of death and similar risk of complications when compared to others altenatives shunts. We emphasize VGB shunt as a safe procedure to be the second option when VPS fails or has contraindications.Keywords: hydrocephalus, ventricular-gallbladder shunt, VGB shunt, VPS, ventriculoperitoneal shunt, ventriculoatrial shunt
Procedia PDF Downloads 72