scholarly journals Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development

2011 ◽  
Vol 3 (02) ◽  
pp. 075-079 ◽  
Author(s):  
Kamlesh Patel ◽  
Sarbjit Singh Jhamb ◽  
Prati Pal Singh
Keyword(s):  
In Silico ◽  
Latent Tuberculosis ◽  
Oxygen Depletion ◽  
In Vitro Models ◽  
Human Infection ◽  
Nutrient Starvation ◽  
Host Immune System ◽  
In Silico Models

ABSTRACTLatent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.

scholarly journals The Combination of Cell Cultured Technology and In Silico Model to Inform the Drug Development

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 704
Author(s):  
Zhengying Zhou ◽  
Jinwei Zhu ◽  
Muhan Jiang ◽  
Lan Sang ◽  
Kun Hao ◽  
...  
Keyword(s):  
Drug Development ◽  
In Silico ◽  
In Vitro Models ◽  
Clinical Settings ◽  
Culture Methods ◽  
Physiologically Based Pharmacokinetic ◽  
Induced Pluripotent ◽  
In Silico Models

Human-derived in vitro models can provide high-throughput efficacy and toxicity data without a species gap in drug development. Challenges are still encountered regarding the full utilisation of massive data in clinical settings. The lack of translated methods hinders the reliable prediction of clinical outcomes. Therefore, in this study, in silico models were proposed to tackle these obstacles from in vitro to in vivo translation, and the current major cell culture methods were introduced, such as human-induced pluripotent stem cells (hiPSCs), 3D cells, organoids, and microphysiological systems (MPS). Furthermore, the role and applications of several in silico models were summarised, including the physiologically based pharmacokinetic model (PBPK), pharmacokinetic/pharmacodynamic model (PK/PD), quantitative systems pharmacology model (QSP), and virtual clinical trials. These credible translation cases will provide templates for subsequent in vitro to in vivo translation. We believe that synergising high-quality in vitro data with existing models can better guide drug development and clinical use.

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

2012 ◽  
Vol 303 (9) ◽  
pp. L733-L747 ◽  
Author(s):  
Brijeshkumar Patel ◽  
Robert Gauvin ◽  
Shahriar Absar ◽  
Vivek Gupta ◽  
Nilesh Gupta ◽  
...  
Keyword(s):  
In Silico ◽  
In Vitro Models ◽  
In Vivo Models ◽  
The Past ◽  
Complex Anatomy ◽  
Human Lungs ◽  
Conventional Cell ◽  
In Silico Models

Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models.

scholarly journals Inherited and Acquired Rhythm Disturbances in Sick Sinus Syndrome, Brugada Syndrome, and Atrial Fibrillation: Lessons from Preclinical Modeling

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3175
Author(s):  
Laura Iop ◽  
Sabino Iliceto ◽  
Giovanni Civieri ◽  
Francesco Tona
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Diseases ◽  
Brugada Syndrome ◽  
In Silico ◽  
Cardiac Fibrosis ◽  
Sick Sinus Syndrome ◽  
In Vitro Models ◽  
Global Functioning

Rhythm disturbances are life-threatening cardiovascular diseases, accounting for many deaths annually worldwide. Abnormal electrical activity might arise in a structurally normal heart in response to specific triggers or as a consequence of cardiac tissue alterations, in both cases with catastrophic consequences on heart global functioning. Preclinical modeling by recapitulating human pathophysiology of rhythm disturbances is fundamental to increase the comprehension of these diseases and propose effective strategies for their prevention, diagnosis, and clinical management. In silico, in vivo, and in vitro models found variable application to dissect many congenital and acquired rhythm disturbances. In the copious list of rhythm disturbances, diseases of the conduction system, as sick sinus syndrome, Brugada syndrome, and atrial fibrillation, have found extensive preclinical modeling. In addition, the electrical remodeling as a result of other cardiovascular diseases has also been investigated in models of hypertrophic cardiomyopathy, cardiac fibrosis, as well as arrhythmias induced by other non-cardiac pathologies, stress, and drug cardiotoxicity. This review aims to offer a critical overview on the effective ability of in silico bioinformatic tools, in vivo animal studies, in vitro models to provide insights on human heart rhythm pathophysiology in case of sick sinus syndrome, Brugada syndrome, and atrial fibrillation and advance their safe and successful translation into the cardiology arena.

Analyses of Gingival Adhesion Molecules in Periodontitis: Theoretical In Silico, Comparative In Vivo, and Explanatory In Vitro Models

2016 ◽  
Vol 87 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Ulvi K. Gürsoy ◽  
Fares Zeidán-Chuliá ◽  
Dogukan Yilmaz ◽  
Vural Özdemir ◽  
Juho Mäki-Petäys ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
In Silico ◽  
In Vitro Models

IN VITRO MODELS OF MYCOBACTERIUM TUBERCULOSIS DORMANCY, AND IN VIVO MODELS OF LATENT TUBERCULOSIS INFECTION

2019 ◽  
Vol 64 (5) ◽  
pp. 299-307
Author(s):  
M. V. Fursov ◽  
I. A. Dyatlov ◽  
V. D. Potapov
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
In Vitro Models ◽  
Tuberculosis Infection ◽  
Published Data ◽  
In Vivo Models ◽  
Dormant State

Modeling of tuberculosis infection is carried out in order to clarify various aspects of the tuberculosis pathogenesis, as well as the testing of new anti-tuberculosis drugs. The characteristic of in vitro models (n = 16) for Mycobacterium tuberculosis dormant state and in vivo models (n = 14) for the latent tuberculosis infection involving several animal species published to date are presented in this review. A brief description of the models and the results obtained by the authors are presented. The analysis of the published data reflects the list of methodological procedures that allow researchers to study the mechanism of the transition of M. tuberculosis cells to a dormant state and reverse to metabolically active state, as well as the process of conversion of active tuberculosis infection to a latent tuberculosis and reactivation.

scholarly journals Current model systems for the study of preeclampsia

2018 ◽  
Vol 243 (6) ◽  
pp. 576-585 ◽  
Author(s):  
ML Martinez-Fierro ◽  
GP Hernández-Delgadillo ◽  
V Flores-Morales ◽  
E Cardenas-Vargas ◽  
M Mercado-Reyes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
In Silico ◽  
Complex Disease ◽  
Model Systems ◽  
Trophoblast Invasion ◽  
Wide Range ◽  
In Silico Models

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal–fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein–protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

scholarly journals Replacement Strategies for Animal Studies in Inhalation Testing

2021 ◽  
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Animal Models ◽  
In Silico ◽  
Particle Deposition ◽  
Drug Testing ◽  
Animal Studies ◽  
Inhalation Exposure ◽  
The Future ◽  
In Silico Models

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

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