scholarly journals Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249594
Author(s):  
Darta Maija Zake ◽  
Janis Kurlovics ◽  
Linda Zaharenko ◽  
Vitalijs Komasilovs ◽  
Janis Klovins ◽  
...  
Keyword(s):  
Blood Flow ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Pbpk Model ◽  
Scale Up ◽  
The Body ◽  
Human Model ◽  
Concentration Time ◽  
Physiologically Based ◽  
Metformin Concentration

Metformin is the primary drug for type 2 diabetes treatment and a promising candidate for other disease treatment. It has significant deviations between individuals in therapy efficiency and pharmacokinetics, leading to the administration of an unnecessary overdose or an insufficient dose. There is a lack of data regarding the concentration-time profiles in various human tissues that limits the understanding of pharmacokinetics and hinders the development of precision therapies for individual patients. The physiologically based pharmacokinetic (PBPK) model developed in this study is based on humans’ known physiological parameters (blood flow, tissue volume, and others). The missing tissue-specific pharmacokinetics parameters are estimated by developing a PBPK model of metformin in mice where the concentration time series in various tissues have been measured. Some parameters are adapted from human intestine cell culture experiments. The resulting PBPK model for metformin in humans includes 21 tissues and body fluids compartments and can simulate metformin concentration in the stomach, small intestine, liver, kidney, heart, skeletal muscle adipose, and brain depending on the body weight, dose, and administration regimen. Simulations for humans with a bodyweight of 70kg have been analyzed for doses in the range of 500-1500mg. Most tissues have a half-life (T1/2) similar to plasma (3.7h) except for the liver and intestine with shorter T1/2 and muscle, kidney, and red blood cells that have longer T1/2. The highest maximal concentrations (Cmax) turned out to be in the intestine (absorption process) and kidney (excretion process), followed by the liver. The developed metformin PBPK model for mice does not have a compartment for red blood cells and consists of 20 compartments. The developed human model can be personalized by adapting measurable values (tissue volumes, blood flow) and measuring metformin concentration time-course in blood and urine after a single dose of metformin. The personalized model can be used as a decision support tool for precision therapy development for individuals.

scholarly journals Mathematical Models for Some Aspects of Blood Microcirculation

Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1020
Author(s):  
Angiolo Farina ◽  
Antonio Fasano ◽  
Fabio Rosso
Keyword(s):  
Blood Flow ◽  
Mathematical Models ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Blood Rheology ◽  
Small Class ◽  
Small Vessels ◽  
Blood Microcirculation ◽  
Peculiar Behavior

Blood rheology is a challenging subject owing to the fact that blood is a mixture of a fluid (plasma) and of cells, among which red blood cells make about 50% of the total volume. It is precisely this circumstance that originates the peculiar behavior of blood flow in small vessels (i.e., roughly speaking, vessel with a diameter less than half a millimeter). In this class we find arteriolas, venules, and capillaries. The phenomena taking place in microcirculation are very important in supporting life. Everybody knows the importance of blood filtration in kidneys, but other phenomena, of not less importance, are known only to a small class of physicians. Overviewing such subjects reveals the fascinating complexity of microcirculation.

Multiscale Modeling of Flow Induced Thrombogenicity Using Dissipative Particle Dynamics and Molecular Dynamics

2013 ◽  
Author(s):  
Danny Bluestein ◽  
João S. Soares ◽  
Peng Zhang ◽  
Chao Gao ◽  
Seetha Pothapragada ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Blood Flow ◽  
Red Blood Cells ◽  
Platelet Activation ◽  
Blood Cells ◽  
Dissipative Particle Dynamics ◽  
Particle Dynamics ◽  
Coagulation Cascade ◽  
Shear Stresses ◽  
Activated Platelets

The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.

Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Human Subjects ◽  
Developmental Regulation ◽  
Physiological Role ◽  
Cell Types ◽  
The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

EFEKTIVITAS PEMBERIAN INFUSED WATER KURMA TERHADAP PENINGKATAN KADAR HEMOGLOBIN REMAJA PUTRI KEBIDANAN POLTEKKES MEDAN TAHUN 2020

2021 ◽  
Vol 2 (1) ◽  
pp. 64-69
Author(s):  
HIJRA HIDAYANA ◽  
Suswati Suswati
Keyword(s):  
Red Blood Cells ◽  
Adolescent Girls ◽  
Blood Cells ◽  
The Body ◽  
Rank Test ◽  
Plain Water ◽  
P Value ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Signed Rank Test

Hemoglobin is the red pigment-protein contained in red blood cells. The function of hemoglobin is to transport oxygen from the lungs and in the bloodstream to be carried to the tissues. Hemoglobin can increase by increasing the intake of iron in the body. One way to increase hemoglobin can be done by giving method Infused Water Dates. Infused water is a drink consisting of plain water with fresh fruit added and soaking or settling together for a certain time. The making of infused water is carried out by soaking for a period of 0 to 12 hours, so that the infused water becomes a liquid medium that carries more nutrients than ordinary water and will be more easily absorbed by cells and distributed throughout the body (Sidauruk, 2018 ). In several studies, it is stated that dates can increase hemoglobin levels in the blood. Where dates contain iron, vitamin A, vitamin C, protein to form red blood cells. With the method, Infused Water the date palm water becomes alkaline so that it can accelerate the absorption process in the body. The purpose of this study was to determine the effectiveness of dates infused water provision to increase hemoglobin levels of midwifery adolescent girls at Medan Health Polytechnic in 2020. This research was quasi-experimental study using the One Group Pretest-Posttest Without Control Design approach. The sample in this study were 20 respondents of midwifery adolescent girls from Medan Health Polytechnic, using the technique of purposive sampling. The statistical test used wa the Wilcoxon Signed Rank Test because the data was not normal. The results of the Wilcoxon Signed Rank Test obtained the value of P-Value = 0.001. So it can be concluded that the date infused water  is effective in increasing hemoglobin levels of midwifery adolescent girls at Medan Health Polytechnic in 2020.   Keywords: Dates Infused Water, Increased Hemoglobin Levels, Girls Adolescent

scholarly journals BIOLOGICAL EFFECTS OF SILICON OXIDE NANOPARTICLES ON BROILER CHICKEN

2020 ◽  
Vol 5 (2) ◽  
pp. 63-71
Author(s):  
Vladimir Nikulin ◽  
Aleksandra Mustafina
Keyword(s):  
Red Blood Cells ◽  
Total Protein ◽  
Blood Cells ◽  
Broiler Chickens ◽  
Broiler Chicken ◽  
Silicon Oxide ◽  
The Body ◽  
Control Group ◽  
The Third ◽  
Experimental Group

The aim of the study is to increase the productive qualities of broiler chickens by including ultrafine silicon oxide into main diet. During the experiment, the biological effect of ultrafine silicon oxide on broiler chickens was estab-lished. Use of ultrafine SiO2 particles for poultry feeding contributed to an increase in the number of red blood cells and content of total protein and albumins. By the end of the experiment, the number of red blood cells in birds in-creased by 17.43% (P≤0.001) – in the blood of birds of the first experimental group, 16.51% (P≤0.01) – the second one, 20.80% (P≤0.001) – the third experimental and 21.71% (P≤0.001) – the fourth experimental group, compared with the indicator of the control group. The amount of total protein in blood serum of chickens of the first and the second experimental groups increased by 1.36-1.39 %, in the third and fourth ones there was a significant (P≤0.05) increase by 5.45 and 3.05%, respectively. The blood glucose content of chickens in the experimental groups is higher by 8.04-23.65% compared to this indicator with ones in the control group. During the experiment feed con-sumption per 1 kg gain of live weight decreased: in the first experimental group by 3.00 % in the second by – 0.50 %, the third – 6.00 % the fourth– by 4.50 %, compared to this with the control group. The chicken’s vibrancy of the first the experimental group was higher by 4.77 %, the second – by 6.20 %, the third – by 19.25 % and the fourth– by 11.59% than in the control one. Consequently, when converting the feed energy into the body energy of a broiler chicken, the energy conversion coefficient of the experimental group of poultry is higher than that of the control one by 7.16-21.76 %. Thus, the most optimal dose for further research was determined.

scholarly journals Development of a Physiologically Based Pharmacokinetic Model for Prediction of Ethanol Concentration-Time Profile in Different Organs

2020 ◽  
Author(s):  
Armin Sadighi ◽  
Lorenzo Leggio ◽  
Fatemeh Akhlaghi
Keyword(s):  
Pbpk Model ◽  
Organ Damage ◽  
Time Profile ◽  
Sensitivity Analyses ◽  
Pbpk Modeling ◽  
Time Curve ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Physiologically Based

Abstract Aims A physiologically based pharmacokinetic (PBPK) modeling approach was used to simulate the concentration-time profile of ethanol (EtOH) in stomach, duodenum, plasma and other tissues upon consumption of beer and whiskey under fasted and fed conditions. Methods A full PBPK model was developed for EtOH using the advanced dissolution, absorption and metabolism (ADAM) model fully integrated into the Simcyp Simulator® 15 (Simcyp Ltd., Sheffield, UK). The prediction performance of the developed model was verified and the EtOH concentration-time profile in different organs was predicted. Results Simcyp simulation showed ≤ 2-fold difference in values of EtOH area under the concentration-time curve (AUC) in stomach and duodenum as compared to the observed values. Moreover, the simulated EtOH maximum concentration (Cmax), time to reach Cmax (Tmax) and AUC in plasma were comparable to the observed values. We showed that liver is exposed to the highest EtOH concentration, faster than other organs (Cmax = 839.50 mg/L and Tmax = 0.53 h), while brain exposure of EtOH (AUC = 1139.43 mg·h/L) is the highest among all other organs. Sensitivity analyses (SAs) showed direct proportion of EtOH rate and extent of absorption with administered EtOH dose and inverse relationship with gastric emptying time (GE) and steady-state volume of distribution (Vss). Conclusions The current PBPK model approach might help with designing in vitro experiments in the area of alcohol organ damage or alcohol-drug interaction studies.

The Use of Wavelets for Wall Removal and Scatter Enhancement in Ultrasound Blood Velocity Profile Measurements

2011 ◽  
Author(s):  
Nathalie Bijnens ◽  
Gregory Koutsouridis ◽  
Marcel Rutten ◽  
Frans van de Vosse ◽  
Peter Brands
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Vessel Wall ◽  
Blood Velocity ◽  
Velocity Estimation ◽  
The Body ◽  
Flow Measurements ◽  
Pass Filter ◽  
Ultrasound Waves ◽  
Blood Flow Measurements

Ultrasound waves, transmitted by a transducer into a body, are reflected and scattered by the materials they encounter in the body. In case of blood flow measurements in an artery, the received signal will contain the information not only from the moving red blood cells, but the reflections from the vessel wall of other soft tissue structures as well. The discrimination between ultrasound signals originating from scattering of red blood cells and reflection of tissue is one of the major problems for blood velocity assessment. Traditionally, in Doppler processing, where the highest blood velocities in the middle of the vessel are estimated, this discrimination is obtained via a high pass filter with a static cut-off frequency related to the maximum frequency content of the reflections. This is illustrated in Fig.1 (top). As illustrated in Fig. 1 (bottom), problems occur for velocity estimation of slowly moving blood cells close to the vessel wall and in case of perpendicular insonification [1]. In these cases, there is no frequency shift in the signal received from scattering on blood cells. Furthermore, the intensity of the reflections from the vessel wall is highest in case of perpendicular insonification. Filtering in these cases is very challenging since it allows the assessment of blood velocity profiles without contrast agents.

scholarly journals A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge Regarding Prevention of Anemia among Adolescent Girls in A Selected Senior Secondary Schools of, Bharatpur

2017 ◽  
Vol 4 (3) ◽  
pp. 192-197
Author(s):  
Ram Gopal ◽  
Tara Chand
Keyword(s):  
Secondary Schools ◽  
Red Blood Cells ◽  
Adolescent Girls ◽  
Blood Cells ◽  
The Body ◽  
Teaching Programme ◽  
Adequate Knowledge ◽  
Structured Teaching ◽  
Senior Secondary Schools ◽  
Senior Secondary

Anemia is a condition in which the number of red blood cells or the amount of hemoglobin is low. Red blood cells contain hemoglobin protein that it enables them to carry oxygen from the lungs and deliver it to all parts of the body. A study conducted to assess the effectiveness of structured teaching programme on knowledge regarding prevention of anemia among adolescent girls in a selected senior secondary schools of Bharatpur. During the study, 60 adolescence girls were selected for them pretest is administered for assessing knowledge. After evaluation pretest score was showing lower knowledge regarding prevention of anemia then structured teaching program on knowledge of prevention from anemia administered after one week post test conducted by using same questionnaire this time girls shows increased knowledge regarding prevention of anemia and they are following healthy food habits for the prevention of anemia. Results showing adequate knowledge various methods are used for measuring the variables such as mean, mode, and standard deviation for significance of demographic variables chi square test were used there is no significant demographic variables.Int. J. Soc. Sc. Manage. Vol. 4, Issue-3: 192-197

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