Role of drug transporters: an overview based on knockout animal model studies

Chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The knowledge of carcinogenic mechanisms provides the scientific rationale for chemoprevention. Epithelial carcinogenesis proceeds through multiple discernible stages of molecular and cellular alterations. Understanding of the multistep nature of carcinogenesis has evolved through highly controlled animal carcinogenesis studies, and these studies have identified three distinct phases: initiation, promotion and progression. Animal model studies have provided evidence that the development of cancer involves many different factors, including alterations in the structures and functions of different genes. Transitions between successive stages can be enhanced or inhibited in the laboratory by different types of agents, such activities providing the fundamental basis for chemoprevention.

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O11.6. THE ROLE OF SERUM GLUTAMATE AND ASPARTATE AS MARKERS FOR CLOZAPINE RESPONSE AND IN THE MECHANISM OF ACTION – DATA FROM HUMAN AND ANIMAL MODEL STUDIES

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.066 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S29-S29

Keyword(s):

Animal Model ◽

Mechanism Of Action ◽

Model Studies ◽

Clozapine Response ◽

Serum Glutamate

Abstract Abstract not included.

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The crucial role of IL-2/IL-2RA-mediated immune regulation in the pathogenesis of type 1 diabetes, an evidence coming from genetic and animal model studies

Immunology Letters ◽

10.1016/j.imlet.2008.03.002 ◽

2008 ◽

Vol 118 (1) ◽

pp. 1-5 ◽

Cited By ~ 27

Author(s):

Dimitry A. Chistiakov ◽

Natalia V. Voronova ◽

Pavel A. Chistiakov

Keyword(s):

Animal Model ◽

Type 1 Diabetes ◽

Immune Regulation ◽

Crucial Role ◽

Model Studies

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The Role of Osteopontin in Amyotrophic Lateral Sclerosis: A Systematic Review

Archives of Neuroscience ◽

10.5812/ans.94205 ◽

2020 ◽

Vol 7 (3) ◽

Cited By ~ 1

Author(s):

Seyed Vahid Mousavi ◽

Elmira Agah ◽

Abbas Tafakhori

Keyword(s):

Animal Model ◽

Amyotrophic Lateral Sclerosis ◽

Cortical Neurons ◽

Human Studies ◽

Cochrane Library ◽

Control Group ◽

Model Studies ◽

Als Patients ◽

Lateral Sclerosis

Context: Osteopontin (OPN) is a matrix phosphoprotein expressed by a variety of tissues and cells, including the immune system and the nervous system. Previous studies have shown that OPN may have a role in neurodegenerative diseases, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Objectives: The present study aimed to systematically review studies investigating the role of OPN in amyotrophic lateral sclerosis (ALS) patients or the disease animal model. Evidence Acquisition: We searched the Cochrane Library, PubMed, Web of Science, and Scopus to find relevant articles published up to January 20, 2019. Both human and animal model studies of ALS were considered. Results: A total of nine articles (four human studies and five animal model studies) were included. Two of the human studies reported that the CSF levels of OPN were higher among ALS patients compared to controls. The other two human studies found that OPN levels in cortical neurons did not differ significantly between ALS cases and the non-neurological control group. One of the studies found that the expression level of OPN in astrocytes was similar between ALS patients and the control group, but the level of microglial OPN significantly increased in ALS cases. Four of the animal model studies reported that the expression of OPN mRNA in spinal cord microglia significantly increased during the disease progression. The remaining animal model study found that OPN was selectively expressed by fast fatigue-resistant and slow motor neurons (MNs), which are resistant to ALS, and that the OPN expression was low among fast-fatigable MNs. Conclusions: Prompt microglial activation is a hallmark pathology of ALS, and OPN is among the most widely expressed proteins by these activated glial cells. Therefore, OPN might have a role in ALS pathogenesis. The existing evidence is not sufficient to justify whether OPN has a neurotoxic or neuroprotective role in ALS. We encourage researchers to investigate the role of OPN in ALS pathogenesis more extensively.

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Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes

Journal of Developmental Biology ◽

10.3390/jdb8010006 ◽

2020 ◽

Vol 8 (1) ◽

pp. 6

Author(s):

Catherine Roberts

Keyword(s):

Animal Model ◽

Cytochrome P450 ◽

Retinoic Acid ◽

Receptor Binding ◽

Genetic Disease ◽

Signalling Pathway ◽

Human Genetic Disease ◽

Model Studies ◽

And Function

This review focuses on the role of the Cytochrome p450 subfamily 26 (CYP26) retinoic acid (RA) degrading enzymes during development and regeneration. Cyp26 enzymes, along with retinoic acid synthesising enzymes, are absolutely required for RA homeostasis in these processes by regulating availability of RA for receptor binding and signalling. Cyp26 enzymes are necessary to generate RA gradients and to protect specific tissues from RA signalling. Disruption of RA homeostasis leads to a wide variety of embryonic defects affecting many tissues. Here, the function of CYP26 enzymes is discussed in the context of the RA signalling pathway, enzymatic structure and biochemistry, human genetic disease, and function in development and regeneration as elucidated from animal model studies.

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Controversies Surrounding the Pathophysiology of Tics

Journal of Child Neurology ◽

10.1177/0883073819862121 ◽

2019 ◽

Vol 34 (13) ◽

pp. 851-862 ◽

Cited By ~ 4

Author(s):

Harvey S. Singer ◽

Farhan Augustine

Keyword(s):

Animal Model ◽

Basal Ganglia ◽

Tourette Syndrome ◽

Model Studies ◽

Complex Interactions ◽

Motor Movements ◽

Premonitory Urge ◽

Underlying Pathophysiology

Tics are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations (phonic productions) that are commonly present in children and are required symptoms for the diagnosis of Tourette syndrome. Despite their frequency, the underlying pathophysiology of tics/Tourette syndrome remains unknown. In this review, we discuss a variety of controversies surrounding the pathophysiology of tics, including the following: Are tics voluntary or involuntary? What is the role of the premonitory urge? Are tics due to excess excitatory or deficient inhibition? Is it time to adopt the contemporary version of the cortico-basal ganglia-thalamocortical (CBGTC) circuit? and Do we know the primary abnormal neurotransmitter in Tourette syndrome? Data from convergent clinical and animal model studies support complex interactions among the various CBGTC sites and neurotransmitters. Advances are being made; however, numerous pathophysiologic questions persist.

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In vitro and in vivo study of the role of WDR11 in idiopathic hypogonadotropic hypogonadism and kallmann syndrome in knockout animal model

International Journal of Surgery ◽

10.1016/j.ijsu.2016.08.247 ◽

2016 ◽

Vol 36 ◽

pp. S34

Author(s):

J.H.Y. Lim ◽

G.H.C. Lim ◽

J.H.C. Lim

Keyword(s):

Animal Model ◽

Hypogonadotropic Hypogonadism ◽

Kallmann Syndrome ◽

In Vivo Study ◽

Idiopathic Hypogonadotropic Hypogonadism ◽

Knockout Animal

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“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649839 ◽

1995 ◽

Vol 74 (03) ◽

pp. 868-873 ◽

Cited By ~ 9

Author(s):

Silvana Arrighi ◽

Roberta Rossi ◽

Maria Giuseppina Borri ◽

Vladimir Lesnikov ◽

Marina Lesnikov ◽

...

Keyword(s):

Heat Treatment ◽

Animal Model ◽

Factor Viii ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Virus Inactivation ◽

Enveloped Viruses ◽

Model Studies ◽

Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

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