Computational bifurcation analysis to find dynamic transitions of the corticotroph model

The corticotroph model is a 7th order nonlinear differential equation system derived for representing the action potential dynamics of corticotrophs; one of the endocrine cells that are responsible for stress regulation. Here we use numerical continuation methods to perform bifurcation analysis since controlling bifurcations in the hormonal dynamics may bring some new insights in the treatment of stress-related disorders. We study the bifurcation structure of the system as a function of the BK-channel dynamic parameters and all maximal conductances. We identify the regions of bistability and bifurcations that shape the transitions between resting, bursting, and spiking behaviors, and which lead to the appearance of bursting which is directly connected to stress regulation. Furthermore, we find that there are two routes to bursting, one is the experimentally observed BK-channel dynamics and the other is Ca2+ channel conductance only. Finally, we discuss how some of the described bifurcations affect the dynamic behavior and can be tested experimentally.No sponso

Quantitative roles of ion channel dynamics on ventricular action potential

Mathematical models for the action potential (AP) generation of the electrically excitable cells including the heart are involved different mechanisms including the voltage-dependent currents with nonlinear time- and voltage-gating properties. From the shape of the AP waveforms to the duration of the refractory periods or heart rhythms are greatly affected by the functions describing the features or the quantities of these ion channels. In this work, a mathematical measure to analyze the regional contributions of voltage-gated channels is defined by dividing the AP into phases, epochs, and intervals of interest. The contribution of each time-dependent current for the newly defined cardiomyocyte model is successfully calculated and it is found that the contribution of dominant ion channels changes substantially not only for each phase but also for different regions of the cardiac AP. Besides, the defined method can also be applied in all Hodgkin–Huxley types of electrically excitable cell models to be able to understand the underlying dynamics better.No sponso

Modeling and analyzing Ca2+ channel dynamics during cardiac action potential

International Conference on Applied Analysis and Mathematical Modeling (2019 : Istanbul, Turkey)We have studied the cardiac action potential model which consists of 26 nonlinear first-order differential equations in a detailed manner computationally. Later, it has been discussed what is the role of the Ca2+ ion channel to the cardiac action potential by applying a mathematical measure called contribution analysis. Computational simulations are done to analyze the roles of Ca2+ gating variables and detailed analysis showed the changing dynamics of Ca2+ channel during a cardiac action potential.No sponso

Histopatološka i molekularna dijagnoza sarkocistoze miokarda u ovaca i imunohistološka korelacija s parazitskim lezijama koje sadrže MMP-2 i MMP-9

This study was aimed at the histopathological and immunohistochemical level investigate cardiac tissue lesions caused by Sarcocystis spp. in sheep, and thereby, to collect detailed information on the presence of these parasites and the pathogenesis of sarcocystosis in ovine animals. PCR, a molecular diagnostic method, was used for the identification of the parasite species. Microscopic examination revealed that out of the 45 ovine cardiac tissue samples examined 23 contained Sarcocystis spp. cysts. The PCR analysis results showed that out of the 23 cardiac tissue specimens infected with sarcocysts, 7 were determined to be infected with Sarcocystis gigantea and 16 with Sarcocystis tenella. Immunohistochemical examination demonstrated that, emiquantitatively, MMP - 9 staining was stronger than MMP - 2 staining in the periphery of the parasite cysts.Cilj je ovog rada bio histopatološko i imunohistokemijsko istraživanje lezija srčanog tkiva uzrokovanih parazitom Sarcocystis spp. u ovaca te prikupljanje detaljnih informacija o prisutnosti ovih parazita i patogenezi sarkocistoze u ovaca. Molekularna dijagnostička metoda PCR upotrijebljena je za identifikaciju parazitskih vrsta. Mikroskopska analiza pokazala je da su od 45 uzoraka srčanog tkiva ovaca 23 sadržavala ciste parazita Sarcocystis spp. Na temelju rezultata PCR analize od 23 uzorka srčanog tkiva invadirana sarkocistama 7 uzoraka bilo je invadirano vrstom Sarcocystis gigantea, a 16 uzoraka vrstom Sarcocystis tenella. Imunohistokemijska pretraga pokazala je da je, semikvantitativno, MMP-9 obojenje bilo jače od obojenja MMP-2 na periferiji cista parazita

Sulfur dioxide derivative prevents the prolongation of action potential during the isoproterenol-induced hypertrophy of rat cardiomyocytes

Exogenous SO2 is toxic especially to the pulmonary and cardiovascular system, similar to nitric-oxide, carbon-monoxide, and hydrogen-sulfide. Endogenous SO2 is produced in many cell types. The SO2 content of the rat heart has been observed to substantially decrease during isoproterenol-induced hypertrophy. This study sought to determine whether an SO2 derivative could inhibit the prolongation of action potentials during the isoproterenol-induced hypertrophy of rat cardiomyocytes and explore the ionic currents. Alongside electrocardiogram recordings, the voltage and current- clamped measurements were conducted in the enzymatically isolated left ventricular cardiomyocytes of Wistar rats. The consistency of the results was evaluated by the novel mathematical electrophysiology model. Our results show that SO2 significantly blocked the prolongation of QT-interval and action potential duration. Furthermore, SO2 did not substantially affect the Na+ currents and did not improve the decreased steady- state and transient outward K+ currents, but it reverted the reduced L-type Ca2+ currents (ICaL) to the physiological levels. Altered inactivation of ICaL was remarkably recovered by SO2. Interestingly, SO2 significantly increased the Ca2+ transients in hypertrophic rat hearts. Our mathematical model also confirmed the mechanism of the SO2 effect. Our findings suggest that the shortening mechanism of SO2 is related to the Ca2+ dependent inactivation kinetics of the Ca2+ current.This study was supported in part by Akdeniz University Scientific Research Coordination Unit (Project No: 2012.02.0122.009) and The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 117F020). These funding sources had no involvement in study design, writing of the report, decision to publish, or the collection, analysis, and interpretation of data

The effect of body mass index and anxiety status on blood pressure in patients admitted to family medicine outpatient clinic

Introduction: Hypertension is a global public health problem that is the leading cause of preventable death in the world and a disease which can cause many morbidities and mortality if not controlled or treated effectively. In many studies, it has been determined that anxiety and body mass index(BMI) are among the factors affecting hypertension. However, different results have been obtained in many studies in terms of the relationship between anxiety and hypertension. This study was carried out with the aim to evaluate the effect of body mass index and anxiety on blood pressure and the factors affecting blood pressure in patients who applied to outpatient clinic of family medicine at Dicle University Faculty of Medicine.Methods: 403 patients aged between 18- 65 years, who applied to outpatient clinic of family medicine at Dicle University Faculty of Medicine between 01.04.2018 and 01.07.2018, were included in this cross-sectional study. The population of the study was the province where the study was carried out, and the sample size was calculated with a power of 80%. The patients' body mass index and anxiety scores from Beck anxiety scale were calculated and measurements of arterial blood pressure were performed. The relationship between BMI, Beck anxiety scores and blood pressure of patients were investigated.Results: Of the participants, 50.1% were male, 49.9% were female and the average age was 34.11 in years. Of the patients, the mean BMI as 25.52 kg/m², the mean anxiety score as 7.40 and the arterial blood pressures as 117.80/75.54 mmHg were measured. It was found that arterial blood pressure raised significantly as the BMI group increased. While the relationship between the severity of anxiety and systolic blood pressure was significant, its relationship with diastolic blood pressure was not significant. There was a positive correlation between BMI, anxiety score and systolic and diastolic blood pressure.Conclusions: According to the results of this study, it was found that the increase in BMI and Beck anxiety scores may be related with increase in arterial blood pressure. This result showed that common health problems in primary care such as anxiety, obesity and hypertension may be associated with each other, and it can be effectively fought against hypertension and its complications with the perspective of family medicine and biopsychosocial approach.Keywords: Anxiety, Hypertension, Blood Pressure, Obesity, Body Mass Inde

Galectin-3 and plasma cytokines in patients with acute myocardial infarction

WOS: 000343954700009PubMed ID: 25316666Objective: To investigate the concentrations of plasma cytokines and Galectin-3 (Gal-3) as inflammatory markers in patients with acute myocardial infarction (AMI). Methods: The study population consisted of 29 patients with AMI and 29 healthy control subjects. We measured Gal-3, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) levels in plasma using enzyme-linked immunosorbent assays (ELISAs). We measured levels of C-reactive protein (CRP) via the nephelometric method. Results: Patients with AMI showed significantly higher plasma Gal-3, TNF-alpha, and IL-6 levels compared with controls. Gal-3 levels were positively and significantly correlated with plasma IL-6, TNF-alpha, and CRP levels in the control and patient groups. Conclusion: Our findings suggest that Gal-3 can be a new circulating biomarker of inflammation associated with AMI

Pulse Parameter Optimization for Ultra High Dose Rate Electron Beams

Purpose: The eFLASH Mobetron delivers UHDR doses at discrete combinations of pulse width (PW), pulse repetition frequency (PRF) and number of pulses (N), which dictate unique combinations of dose and dose rates. Currently, obtaining pulse parameters for the desired dose and dose rate is a cumbersome manual process involving creating, updating and looking up values in large spreadsheets for every collimator. The purpose of this work is to present a MATLAB based pulse parameter optimizer tool to match intended dose and dose rate more precisely and efficiently. Methods: A constrained optimization problem for the dose and dose rate cost function was modelled as a mixed integer problem in MATLAB. The beam and machine data required for the software were acquired using GafChromic film and Alternating Current Current Tranformers (ACCTs), including dose per pulse for every collimator, pulse widths measured using ACCT, and air gap factors. Results: Using N, PRF, PW and air gap factors as the parameters, the software was created to optimize for dose and dose rate. By largely automating this dose calculation part, we have greatly reduced safety concerns associated with manual look up and calculation of these parameters, especially when many subjects at different doses and dose rates are to be irradiated. Conclusion: A pulse parameter optimization tool was built in MATLAB for the eFLASH Mobetron to increase efficiency in the dose, dose rate and pulse parameter prescription proces

The efficacy of chloroquine treatment against naturally occuring Giardia duodenalis infection in lambs

Objective. The aim of the present study was to determine the efficacy of Chloroquine (Cq), an antimalarial medicine, administered at a dose of 2.5 mg/kg, orally, during 5 consecutive days, in Sakiz and Merino lambs naturally infected with Giardia duodenalis. Materials and methods. To this extent weaned 10 weeks of aged lambs were enrolled and randomly assigned into two groups based on treatment (group C, n=18 lambs treated with Cq) and placebo (group P, n=8 untreated control animals). Diagnosis was based on detection of trophozoit and/or cysts on fecal flotation. Cyst count per gram feces (days 0, 3, 7 and 10) was analyzed among groups. Results. During the trial, regarding the efficacy of Cq on days 3., 7., and 10. There was significant (p<0.01) reduction in cyst excretion; whereas evaluation of mean geometric cyst excretion revealed 100% reduction. Conclusions. There was a very high (100%) reduction in cyst excretion in the Cq treatment group compared to the positive untreated control group on days 3, 7 and 10, resulting in a significant (p<0.001) reduction, making Cq, safety, and thus highly effective treatment option of lambs with naturally occuring giardiasis. Objetivo. El objetivo del presente estudio fue determinar la eficacia de la cloroquina, un medicamento contra la malaria, administrado a una dosis de 2.5 mg/kg, por vía oral, durante 5 días consecutivos, en Corderos Sakiz y Merino infectados naturalmente con Giardia duodenalis. Materiales y metodos. En esta medida destetados 10 semanas de edad fueron incluidos y asignados al azar en dos grupos sobre la base del tratamiento (grupo C, n = 18 corderos tratados con cloroquina) y placebo (grupo P, n = 8 animales de control no tratados). El diagnóstico se basa en la detección de trophozoit y/o quistes en la flotación fecal. Quiste recuento por gramo de heces (día 0, 3, 7 y 10) se analizó entre los grupos. Resultados. Respecto a la eficacia de la cloroquina en los días 3, 7 y 10 existió una reducción significativa (p<0.01) en la excreción de quistes; mientras que la evaluación de la media de la excreción Rev.MVZ Córdoba 21(2):5328-5335, 2016. ISSN: 0122-0268 ORIGINAL 5329 de quistes reveló una reducción del 100%. Conclusiones. Durante el estudio hubo una reducción del 100% en la excreción de quistes en el grupo de tratamiento con cloroquina en comparación con el grupo control no tratado positivo en los días 3, 7 y 10, lo que resulta en una disminución significativa (p<0.001) por lo que la cloroquina razonablemente es una opción de tratamiento por el costo, seguridad, y por lo tanto muy eficaz de corderos infectados naturalmente con giardiasis

The 33-year Retrospective Analysis of Esophageal Carcinomas: Cerrahpaşa Experience

Aim:Esophageal cancer is a fatal disease where the majority of patients are diagnosed at an advanced stage. In this study, we aimed to present the demographic and clinicopathological characteristics of patients who were operated for esophageal cancer.Materials and Methods:A total of 847 patients who underwent surgery, chemoradiotherapy, or palliative procedures for esophageal pathology between the years of 1985 and 2018 were retrospectively analyzed. Age, gender, tumor location, histopathology, surgical technique, and chemoradiotherapy history of patients were analyzed.Results:In the study, 488 patients were male (60.5%) and 319 were female (39.5%). The ratio of males and females was 1.52. The average age was 58.6 years, and 80.1% were older than 50 years. The most common pathological material obtained was squamous cell carcinoma (67.5%), followed by adenocarcinoma (27.7%). Total esophagectomy was performed in 435 patients; distal esophagectomy was performed in 38 patients. Transhiatal esophagectomy (n=271, 62.2%) was the most common procedure that was performed.Conclusion:Esophagectomy is the primary treatment modality for esophageal cancers. When determining the optimal treatment, appropriate patient selection, staging, and risk assessment should be made. Patient-specific treatment should be planned with a multidisciplinary approach