• Toxicological Research
• /
• v.18 no.4
• /
• pp.311-324
• /
• 2002

Toxicokinetic studies are intended to provide critical evaluation of drug disposition at toxico-logical doses and help understand the relationship between blood or tissue levels and the time course of toxic events. Relatively high dose levels wed in toxicokinetics, compared to pharmacokinetics, complicates absorption, protein binding, metabolism and elimination processes. In this mini review, frequently wed toxicokinetic models such as linear compartment models, physiological models, and nonlinear kinetic mod-ec are introduced. In addition, optimization of toxicokinetic studies, their role in the drug development process, and prediction oj human toxicokinetics based on animal data by interspecies scaling are briefly discussed.

• Sleep Medicine and Psychophysiology
• /
• v.16 no.1
• /
• pp.5-9
• /
• 2009

Relatively little is known about the neurobiology of insomnia, despite its wide prevalence and broad medical impact. Although much is still to be learned about the pathophysiology of the disorder, identification, systematic assessment, and appropriate treatment are clearly beneficial to patients. Recent research, using quantitative EEG, polysomnography (PSG), multiple sleep latency test (MSLT) and neuroimaging techniques, suggests that some broad areas can be identified as possible pathophysiological models. Sleep-wake homeostat model hypothesizes a failure in homeostatic regulation of sleep, an attenuated increase in sleep drive with time awake, and/or defective sensing of sleep need. Circadian clock model hypothesizes a dysfunctional circadian clock, resulting in changes in the timing of sleep-wake propensity that are incompatible with normal sleep. Intrinsic sleep-wake state mechanism model suggests that abnormal function of insomnia comprises the systems responsible for expression of the sleep states themselves. Extrinsic over-ride mechanism (stress-response) model suggests that insomnia reflects the consequences of overactivity of one of the systems considered "extrinsic" to normal sleep-wake control. Many current therapies for insomnia are based on these physiological models. Several attempts have been made to create a physiological model that would explain this disorder and could be used as a foundation for treatment. However, it appeared that no model can fully explain and clarify all aspects of insomnia. Future research should be necessary to expand our knowledge on the biological dimensions of insomnia.

• Journal of the Korean Society of Visualization
• /
• v.9 no.3
• /
• pp.65-70
• /
• 2011

Three major physiological functions of nose can be described as air-conditioning, filtering and smelling. Detailed knowledge of airflow characteristics in nasal cavities is essential to understanding of the physiological and pathological aspects of nasal breathing. In our laboratory, a series of experimental investigations have been conducted on the airflows in normal and abnormal nasal cavity models by means of PIV under both constant and periodic flow conditions. In this work, more specifically experimental and numerical results on the surgically modified inferior turbinate model were presented. With the high resolution CT data and a careful treatment of the model surface under the ENT doctor's advice yielded quite sophisticated cavity models for the PIV experiment. Physiological nature of the airflow was discussed in terms of velocity distribution and vortical structure for constant inspirational flow. Since the inferior and middle turbinate are key determinants of nasal airflow, the turbinectomy obviously altered the main stream direction. This phenomenon may cause local changes in physiological function and the flow resistance.

• Journal of Preventive Medicine and Public Health
• /
• v.46 no.2
• /
• pp.74-81
• /
• 2013

Objectives: The objective of this study was to evaluate the performance of risk-adjusted mortality models for colorectal cancer surgery. Methods: We investigated patients (n=652) who had undergone colorectal cancer surgery (colectomy, colectomy of the rectum and sigmoid colon, total colectomy, total proctectomy) at five teaching hospitals during 2008. Mortality was defined as 30-day or in-hospital surgical mortality. Risk-adjusted mortality models were constructed using claims data (basic model) with the addition of TNM staging (TNM model), physiological data (physiological model), surgical data (surgical model), or all clinical data (composite model). Multiple logistic regression analysis was performed to develop the risk-adjustment models. To compare the performance of the models, both c-statistics using Hanley-McNeil pair-wise testing and the ratio of the observed to the expected mortality within quartiles of mortality risk were evaluated to assess the abilities of discrimination and calibration. Results: The physiological model (c=0.92), surgical model (c=0.92), and composite model (c=0.93) displayed a similar improvement in discrimination, whereas the TNM model (c=0.87) displayed little improvement over the basic model (c=0.86). The discriminatory power of the models did not differ by the Hanley-McNeil test (p>0.05). Within each quartile of mortality, the composite and surgical models displayed an expected mortality ratio close to 1. Conclusions: The addition of clinical data to claims data efficiently enhances the performance of the risk-adjusted postoperative mortality models in colorectal cancer surgery. We recommended that the performance of models should be evaluated through both discrimination and calibration.

• Annals of Clinical Neurophysiology
• /
• v.1 no.2
• /
• pp.147-153
• /
• 1999

Hippocampal slice models can be a powerful tool to study the mechanism of partial epilepsy. Despite the loss of connection with the rest of the brain, in vitro hippocampal slice preparations allow detailed physiological and pharmacological studies, which would be impossible, in vivo. There are several methods to induce electrographic seizures on hippocampal slice models. Those are electrical pulse train stimulation, 0 $Mg^{2+}$ artificial cerebrational fluid and high concentration of extracelluar $K^+$ on bath. Among them, the electrically triggered seizure may mimic the physiological communication between neuronal populations without any deterioration of normal physiologic and chemical status of the hippocampal slice models. Presumably, such communication from hyperexcitable areas to other neuronal populations is involved in the development of epilepsy. Electrographic seizures in hippocampal slice models occur in the network of neurons that are involved in epileptic seizures in the hippocampus in vivo. Because these models have many advantages and are very valuable to research of epileptogenesis on partial epilepsy, I would like to introduce the electrophysiological methods to induce electrographic seizure or epilepsy on hippocampal slice models briefly in this paper.

• Archives of Pharmacal Research
• /
• v.10 no.4
• /
• pp.250-257
• /
• 1987

The development of physiologically based pharmacokinetic model for drug distribution and excretion is described. The physiological modeling procedure is useful in animal and clinical applications to obtain fundamental knowledge of the transport and metabolism of a substance in vivo. In this paper a review of physiologically based pharmacokinetics is presented in the hope of understanding and increasing the use of this modelling technique. The method of model development and the composition of equations based on the different models are explained. For the better understanding a physiological pharmacokinetic model of tenoxicam disposition in the rat is presented as an example of flow limited model.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.6
• /
• pp.441-452
• /
• 2020

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

• Korea-Australia Rheology Journal
• /
• v.21 no.1
• /
• pp.39-46
• /
• 2009

Atherosclerosis is a disease that narrows, thickens, hardens, and restructures a blood vessel due to substantial plaque deposit. The geometric models of the considered stenotic blood flow are three different types of constriction of cross-sectional area of blood vessel; 25%, 50%, and 75% of constriction. The computational model with the fluid-structure interaction is introduced to investigate the wall shear stresses, blood flow field and recirculation zone in the stenotic vessels. The velocity profile in a compliant stenotic artery with various constrictions is subjected to prescribed physiologic waveform. The computational simulations were performed, in which the physiological flow through a compliant axisymmetric stenotic blood vessel was solved using commercial software ADINA 8.4 developed by finite element method. We demonstrated comparisons of the wall shear stress with or without the fluid-structure interaction and their velocity profiles under the physiological flow condition in the compliant stenotic artery. The present results enhance our understanding of the hemodynamic characteristics in a compliant stenotic artery.

• Korean journal of medical education
• /
• v.30 no.4
• /
• pp.359-364
• /
• 2018

Purpose: Learning physiological concepts and their practical applications in the appropriate contexts remains a great challenge for undergraduate medical students. Hence the present study aimed to analyze the learning experience of undergraduate medical students during an active learning process of 'preparation of models' depicting physiological concepts. Methods: A total of 13 groups, involving 55 undergraduate medical students with three to five individuals in each group, were involved in model preparation. A total of 13 models were exhibited by the students. The students shared their learning experiences as responses to an open-ended questionnaire. The students' responses were analyzed and generalized comments were generated. Results: Analysis of the results showed that the act of 'model preparation' improved concept understanding, retention of knowledge, analytical skills, and referral habits. Further, the process of 'model preparation' could satisfy all types of sensory modality learners. Conclusion: This novel active method of learning could be highly significant in students' understanding and learning physiology concepts. This approach could be incorporated in the traditional instructor-centered undergraduate medical curriculum as a way to innovate it.

• Molecules and Cells
• /
• v.44 no.12
• /
• pp.861-878
• /
• 2021

The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.