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Annual Review of Biomedical Engineering 2012In vitro studies of vascular physiology have traditionally relied on cultures of endothelial cells, smooth muscle cells, and pericytes grown on centimeter-scale plates,... (Review)
Review
In vitro studies of vascular physiology have traditionally relied on cultures of endothelial cells, smooth muscle cells, and pericytes grown on centimeter-scale plates, filters, and flow chambers. The introduction of microfluidic tools has revolutionized the study of vascular physiology by allowing researchers to create physiologically relevant culture models, at the same time greatly reducing the consumption of expensive reagents. By taking advantage of the small dimensions and laminar flow inherent in microfluidic systems, recent studies have created in vitro models that reproduce many features of the in vivo vascular microenvironment with fine spatial and temporal resolution. In this review, we highlight the advantages of microfluidics in four areas: the investigation of hemodynamics on a capillary length scale, the modulation of fluid streams over vascular cells, angiogenesis induced by the exposure of vascular cells to well-defined gradients in growth factors or pressure, and the growth of microvascular networks in biomaterials. Such unique capabilities at the microscale are rapidly advancing the understanding of microcirculatory dynamics, shear responses, and angiogenesis in health and disease as well as the ability to create in vivo-like blood vessels in vitro.
Topics: Animals; Biocompatible Materials; Biomechanical Phenomena; Biomedical Engineering; Blood Coagulation; Cardiovascular Physiological Phenomena; Cell Culture Techniques; Cells, Cultured; Erythrocytes; Hemodynamics; Humans; Mice; Microcirculation; Microfluidics; Neovascularization, Pathologic; Neovascularization, Physiologic; Rats; Shear Strength; Stress, Mechanical
PubMed: 22540941
DOI: 10.1146/annurev-bioeng-071811-150052 -
Current Drug Metabolism 2023Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a... (Review)
Review
Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.
Topics: Humans; Aged; Pharmaceutical Preparations; Models, Biological; Computer Simulation
PubMed: 37165496
DOI: 10.2174/1389200224666230509104404 -
Clinical Calcium Feb 2014Calcium deposition can be observed in many tissues in addition to bones and teeth which physiologically calcify. This unphysiological calcification can damage several... (Review)
Review
Calcium deposition can be observed in many tissues in addition to bones and teeth which physiologically calcify. This unphysiological calcification can damage several organs. It has been shown that vascular calcification which is a risk factor for cardiovascular events develops through similar mechanisms to physiological calcification. Further studies to clarify detailed mechanisms of calcification are necessary to develop measures that inhibit unphysiological ectopic calcification without affecting physiological calcification in bones and teeth.
Topics: Animals; Bone Density; Bone and Bones; Calcification, Physiologic; Calcium; Humans; Muscle, Smooth, Vascular; Vascular Diseases
PubMed: 24473351
DOI: No ID Found -
Frontiers in Immunology 2020The axonal guidance molecules, semaphorins, have been described to function both physiologically and pathologically outside of the nervous system. In this review, we... (Review)
Review
The axonal guidance molecules, semaphorins, have been described to function both physiologically and pathologically outside of the nervous system. In this review, we focus on the vertebrate semaphorins found in classes 3 through 7 and their roles in vascular development and autoimmune diseases. Recent studies indicate that while some of these vertebrate semaphorins promote angiogenesis, others have an angiostatic function. Since some semaphorins are also expressed by different immune cells and are known to modulate immune responses, they have been implicated in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. We conclude this review by addressing strategies targeting semaphorins as potential therapeutic agents for angiogenesis and autoimmune diseases.
Topics: Animals; Autoimmune Diseases; Cell Adhesion Molecules; Humans; Neovascularization, Physiologic; Nerve Tissue Proteins; Neuropilins; Semaphorins
PubMed: 32210960
DOI: 10.3389/fimmu.2020.00346 -
Arteriosclerosis, Thrombosis, and... Aug 2010Estrogens, and in particular 17beta-estradiol (E2), play a pivotal role in sexual development and reproduction and are also implicated in a large number of physiological... (Review)
Review
Estrogens, and in particular 17beta-estradiol (E2), play a pivotal role in sexual development and reproduction and are also implicated in a large number of physiological processes, including the cardiovascular system. Both acetylcholine-induced and flow-dependent vasodilation are preserved or potentiated by estrogen treatment in both animal models and humans. Indeed, E2 increases the endothelial production of nitric oxide and prostacyclin and prevents early atheroma through endothelial-mediated mechanisms. Furthermore, whereas it prevents endothelial activation, E2 potentiates the ability of several subpopulations of the circulating or resident immune cells to produce proinflammatory cytokines. The balance between these 2 actions could determine the final effect in a given pathophysiological process. E2 also promotes endothelial healing, as well as angiogenesis. Estrogen actions are essentially mediated by 2 molecular targets: estrogen receptor-alpha (ERalpha) and ERbeta. The analysis of mouse models targeted for ERalpha or ERbeta demonstrated a prominent role of ERalpha in vascular biology. ERalpha directly modulates transcription of target genes through 2 activation functions (AFs), AF-1 and AF-2. Interestingly, an AF-1-deficient ERalpha isoform can be physiologically expressed in the endothelium and appears sufficient to mediate most of the vasculoprotective actions of E2. In contrast, AF-1 is necessary for the E2 actions in reproductive targets. Thus, it appears conceivable to uncouple the vasculoprotective and sexual actions with appropriate selective ER modulators.
Topics: Animals; Cardiovascular Diseases; Disease Progression; Endothelium, Vascular; Estradiol; Female; Humans; Inflammation Mediators; Male; Mice; Neovascularization, Physiologic; Receptors, Estrogen; Sex Factors; Sexual Development; Signal Transduction; Wound Healing
PubMed: 20631350
DOI: 10.1161/ATVBAHA.109.191221 -
Clinical Pharmacokinetics Apr 2020Developmental physiology can alter pharmacotherapy in preterm populations. Because of ethical and clinical constraints in studying this vulnerable age group,...
BACKGROUND
Developmental physiology can alter pharmacotherapy in preterm populations. Because of ethical and clinical constraints in studying this vulnerable age group, physiologically based pharmacokinetic models offer a viable alternative approach to predicting drug pharmacokinetics and pharmacodynamics in this population. However, such models require comprehensive information on the changes of anatomical, physiological and biochemical variables, where such data are not available in a single source.
OBJECTIVE
The objective of this study was to integrate the relevant physiological parameters required to build a physiologically based pharmacokinetic model for the preterm population.
METHODS
Published information on developmental preterm physiology and some drug-metabolising enzymes were collated and analysed. Equations were generated to describe the changes in parameter values during growth.
RESULTS
Data on organ size show different growth patterns that were quantified as functions of bodyweight to retain physiological variability and correlation. Protein binding data were quantified as functions of age as the body weight was not reported in the original articles. Ontogeny functions were derived for cytochrome P450 1A2, 3A4 and 2C9. Tissue composition values and how they change with age are limited.
CONCLUSIONS
Despite the limitations identified in the availability of some tissue composition values, the data presented in this article provide an integrated resource of system parameters needed for building a preterm physiologically based pharmacokinetic model.
Topics: Body Composition; Body Weight; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP3A; Female; Gestational Age; Growth and Development; Humans; Inactivation, Metabolic; Infant, Newborn; Male; Meta-Analysis as Topic; Metabolic Clearance Rate; Models, Biological; Organ Size; Pharmacokinetics; Predictive Value of Tests; Premature Birth; United Kingdom
PubMed: 31583613
DOI: 10.1007/s40262-019-00825-6 -
Prehospital and Disaster Medicine 2010Attendance at UK emergency departments is rising steadily despite the proliferation of alternative unscheduled care providers. Evidence is mixed on the willingness of...
INTRODUCTION
Attendance at UK emergency departments is rising steadily despite the proliferation of alternative unscheduled care providers. Evidence is mixed on the willingness of emergency medical services (EMS) providers to decline to transport patients and the safety of incorporating such an option into EMS provision. Physiologically based Early Warning Scores are in use in many hospitals and emergency departments, but not yet have been proven to be of benefit in the prehospital arena.
HYPOTHESIS
The use of a physiological-social scoring system could safely identify patients calling EMS who might be diverted from the emergency department to an alternative, unscheduled, care provider.
METHODS
This was a retrospective, cohort study of patients with a presenting complaint of "shortness of breath" or "difficulty breathing" transported to the emergency department by EMS. Retrospective calculation of a physiological social score (PMEWS) based on first recorded data from EMS records was performed. Outcome measures of hospital admission and need for physiologically stabilizing treatment in the emergency department also were performed.
RESULTS
A total of 215 records were analyzed. One hundred thirty-nine (65%) patients were admitted from the emergency department or received physiologically stabilizing treatment in the emergency department. Area Under the Receiver Operating Characteristic Curve (AUROC) for hospital admission was 0.697 and for admission or physiologically stabilizing treatment was 0.710. No patient scoring<2 was admitted or received stabilizing treatment.
CONCLUSIONS
Despite significant over-triage, this system could have diverted 79 patients safely from the emergency department to alternative, unscheduled, care providers.
Topics: Ambulances; Ambulatory Care Facilities; Decision Making; Dyspnea; Emergency Service, Hospital; Humans; Patient Admission; Retrospective Studies; Severity of Illness Index; Triage; United Kingdom
PubMed: 20845317
DOI: 10.1017/s1049023x00008268 -
The Medical Clinics of North America Jan 1987The decline and eventual cessation of estrogen production by the ovary at menopause are reflected physiologically in tissues with estrogen receptors. The rate of decline... (Review)
Review
The decline and eventual cessation of estrogen production by the ovary at menopause are reflected physiologically in tissues with estrogen receptors. The rate of decline of hormones is quite variable and often relates to symptoms experienced. At menopause women still have one third of their life expectancy ahead of them. The physician must determine which symptoms are aging, physiologic changes resulting from estrogen deprivation and which may herald more serious pathology in need of diagnosis and treatment. The knowledgeable physician can give good explanation, which is sometimes as beneficial as medications. Hormone replacement therapy may improve physiologic function of some tissues and relieve symptoms. When hormones are given for clear indications in as safe a method as possible and with adequate monitoring, the woman will have her symptoms relieved and will be grateful for her sense of well-being and ability to enjoy life.
Topics: Adult; Aging; Breast; Climacteric; Female; Humans; Menopause; Menopause, Premature; Menstruation; Middle Aged; Ovary; Skin Physiological Phenomena; Urinary Tract Physiological Phenomena; Uterus; Vagina; Vulva
PubMed: 3543538
DOI: 10.1016/s0025-7125(16)30879-3 -
Environmental Pollution (Barking, Essex... Nov 2022Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs)... (Meta-Analysis)
Meta-Analysis
Development of physiologically-based toxicokinetic-toxicodynamic (PBTK-TD) model for 4-nonylphenol (4-NP) reflecting physiological changes according to age in males: Application as a new risk assessment tool with a focus on toxicodynamics.
Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs) related to reproductive toxicity in males is very important in risk-level assessment and management of 4-NP. This study aimed to develop a physiologically-based-toxicokinetic-toxicodynamic (PBTK-TD) model that added a TD prostate model to the previously reported 4-n-nonylphenol (4-n-NP) physiologically-based-pharmacokinetic (PBPK) model. Modeling was performed under the assumption of similar TKs between 4-n-NP and 4-NP because TK experiments on 4-NP, a random-mixture, are practically difficult. This study was very important to quantitatively predict the TKs and TDs of 4-NP by age at exposure using an advanced PBTK-TD model that reflected physiological-changes according to age. TD-modeling was performed based on the reported toxic effects of 4-NP on RWPE-1 cells, a human-prostate-epithelial-cell-line. Through a meta-analysis of reported human physiological data, body weight, tissue volume, and blood flow rate patterns according to age were mathematically modeled. These relationships were reflected in the PBTK-TD model for 4-NP so that the 4-NP TK and TD changes according to age and their differences could be confirmed. Differences in TK and TD parameters of 4-NP at various ages were not large, within 3.61-fold. Point-of-departure (POD) and reference-doses for each age estimated using the model varied as 426.37-795.24 and 42.64-79.52 μg/kg/day, but the differences (in POD or reference doses between ages) were not large, at less than 1.87-times. The PBTK-TD model simulation predicted that even a 100-fold 4-NP POD dose would not have large toxicity to the prostate. With a focus on TDs, the predicted maximum possible exposure of 4-NP was as high as 6.06-23.60 mg/kg/day. Several toxicity-related values estimated by the dose-response curve were higher than those calculated, depending upon the PK or TK, which would be useful as a new exposure limit for prostate toxicity of 4-NP.
Topics: Humans; Male; Models, Biological; Phenols; Risk Assessment; Toxicokinetics
PubMed: 36030954
DOI: 10.1016/j.envpol.2022.120041 -
Advanced Materials (Deerfield Beach,... Sep 2021In mammals, physiological respiration involves respiratory cycles of inhaled and exhaled breaths, which has traditionally been an underutilized resource potentially... (Review)
Review
In mammals, physiological respiration involves respiratory cycles of inhaled and exhaled breaths, which has traditionally been an underutilized resource potentially encompassing a wealth of physiologically relevant information as well as clues to potential diseases. Recently, triboelectric nanogenerators (TENGs) have been widely adopted for self-powered respiration monitoring owing to their compelling features, such as decent biocompatibility, wearing comfort, low-cost, and high sensitivity to respiration activities in the aspect of low frequency and slight amplitude body motions. Physiological respiration behaviors and exhaled chemical regents can be precisely and continuously monitored by TENG-based respiration sensors for personalized health care. This article presents an overview of TENG enabled self-powered respiration monitoring, with a focus on the working principle, sensing materials, functional structures, and related applications in both physical respiration motion detection and chemical breath analysis. Concepts and approaches for acquisition of physical information associated with respiratory rate and depth are covered in the first part. Then the sensing mechanism, theoretical modeling, and applications related to detection of chemicals released from breathing gases are systemically summarized. Finally, the opportunities and challenges of triboelectric effect enabled self-powered respiration monitoring are comprehensively discussed and criticized.
Topics: Electric Power Supplies; Monitoring, Physiologic; Nanotechnology; Wearable Electronic Devices
PubMed: 34240473
DOI: 10.1002/adma.202101262