scholarly journals Brain and Plasma Riluzole Pharmacokinetics: Effect of Minocycline Combination

2009 ◽  
Vol 12 (2) ◽  
pp. 209 ◽  
Author(s):  
Aline Milane ◽  
Lionel Tortolano ◽  
Christine Fernandez ◽  
Gilbert Bensimon ◽  
Vincent Meininger ◽  
...  
Keyword(s):  
Animal Model ◽  
Fold Increase ◽  
Phase Iii ◽  
Beneficial Effects ◽  
P Glycoprotein ◽  
High Doses ◽  
Kinetics Of ◽  
The Brain ◽  
Phase Iii Studies ◽  
Lateral Sclerosis

PURPOSE: amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by the loss of motorneurons. The only drug approved is riluzole. Minocycline is an antibiotic with numerous neuroprotective properties. riluzole and minocycline were given to an animal model of ALS and had beneficial effect on the disease. The combination was then tested in humans in phase II and phase III studies with less beneficial effects and a faster decline of the disease in the group treated with minocycline. In a previous study, we showed that riluzole is transported out of the brain by the P-glycoprotein at the blood-brain barrier level. METHODS: in this work, we studied in CF1 mice, the plasmatic and cerebral pharmacokinetics of riluzole combined or not with minocycline. RESULTS: our results showed that the kinetics of riluzole are not linear with dose, but that cerebral AUC0-∞ increase proportionally with plasmatic AUC0-∞. At the dose of 10 mg/kg, the cerebral AUC0-∞ /plasmatic AUC0-∞ ratio was 4.6 in mdr1a (-/-) mice and 2.4 in mdr1a (+/+) mice. The combination of minocycline (170 mg/kg) and riluzole (10 mg/kg) induced a 2 fold increase in the cerebral AUC0-∞ of riluzole and induced a neuromuscular toxicity in mice. This effect of minocycline was not found at low concentration (10 mg/kg of minocycline). CONCLUSIONS: if our results are confirmed in humans, riluzole cerebral concentrations could be predicted by plasmatic concentrations. Furthermore, the combination of high doses of minocycline with riluzole could induce neurological toxicity that lead to deceiving results in ALS clinical studies.

scholarly journals Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

2009 ◽  
Vol 45 (4) ◽  
pp. 607-618 ◽  
Author(s):  
Graciela Cristina dos Santos ◽  
Lusânia Maria Greggi Antunes ◽  
Antonio Cardozo dos Santos ◽  
Maria de Lourdes Pires Bianchi
Keyword(s):  
Neurodegenerative Diseases ◽  
Health Risks ◽  
Coenzyme Q10 ◽  
Cellular Respiration ◽  
Irreversible Loss ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Electron Transportation ◽  
The Brain ◽  
Lateral Sclerosis

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

P-glycoprotein expression and function are increased in an animal model of amyotrophic lateral sclerosis

2010 ◽  
Vol 472 (3) ◽  
pp. 166-170 ◽  
Author(s):  
Aline Milane ◽  
Christine Fernandez ◽  
Luc Dupuis ◽  
Marion Buyse ◽  
Jean-Philippe Loeffler ◽  
...  
Keyword(s):  
Animal Model ◽  
Amyotrophic Lateral Sclerosis ◽  
P Glycoprotein ◽  
And Function ◽  
Lateral Sclerosis

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington’s disease.

2019 ◽  
Author(s):  
F Elifani ◽  
E Amico ◽  
G Pepe ◽  
L Capocci ◽  
S Castaldo ◽  
...  
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Body Weight Loss ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Human Pathology ◽  
The Brain

Abstract Huntington’s disease (HD) has traditionally been described as a disorder purely of the brain, however evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction, preservation of GI emptying, and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

scholarly journals Imaging the Impact of the P-Glycoprotein (ABCB1) Function on the Brain Kinetics of Metoclopramide

2015 ◽  
Vol 57 (2) ◽  
pp. 309-314 ◽  
Author(s):  
G. Pottier ◽  
S. Marie ◽  
S. Goutal ◽  
S. Auvity ◽  
M.-A. Peyronneau ◽  
...  
Keyword(s):  
P Glycoprotein ◽  
The Impact ◽  
Kinetics Of ◽  
The Brain

scholarly journals Impact of P-Glycoprotein Function on the Brain Kinetics of the Weak Substrate 11C-Metoclopramide Assessed with PET Imaging in Humans

2019 ◽  
Vol 60 (7) ◽  
pp. 985-991 ◽  
Author(s):  
Nicolas Tournier ◽  
Martin Bauer ◽  
Verena Pichler ◽  
Lukas Nics ◽  
Eva-Maria Klebermass ◽  
...  
Keyword(s):  
Pet Imaging ◽  
P Glycoprotein ◽  
Kinetics Of ◽  
The Brain

scholarly journals Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients

2019 ◽  
Vol 79 (3) ◽  
pp. 266-276
Author(s):  
Erwin A van Vliet ◽  
Anand M Iyer ◽  
Lucia Mesarosova ◽  
Hilal Çolakoglu ◽  
Jasper J Anink ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Abc Transporters ◽  
Breast Cancer Resistance Protein ◽  
Cellular Distribution ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
Als Patients ◽  
The Brain ◽  
Lateral Sclerosis

Abstract For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular distribution of the ABC transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) using immunohistochemistry in spinal cord (SC), motor cortex, and cerebellum from a large cohort of genetically well characterized ALS patients (n = 25) and controls (n = 14). The ALS group included 17 sporadic (sALS) and 8 familial (fALS) patients. Strong P-gp expression was observed in endothelial cells in both control and ALS specimens. Immunohistochemical analysis showed higher P-gp expression in reactive astroglial cells in both gray (ventral horn) and white matter of the SC, as well as in the motor cortex of all ALS patients, as compared with controls. BCRP expression was higher in glia in the SC and in blood vessels and glia in the motor cortex of ALS patients, as compared with controls. P-gp and BCRP immunoreactivity did not differ between sALS and fALS cases. The upregulation of both ABC transporters in the brain may explain multidrug resistance in ALS patients and has implications for the use of both approved and experimental therapeutics.

Levels of membrane fluidity in the spinal cord and the brain in an animal model of amyotrophic lateral sclerosis

2011 ◽  
Vol 43 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Francisco Javier Miana-Mena ◽  
Eduardo Piedrafita ◽  
Cristina González-Mingot ◽  
Pilar Larrodé ◽  
María Jesús Muñoz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Animal Model ◽  
Amyotrophic Lateral Sclerosis ◽  
Membrane Fluidity ◽  
The Brain ◽  
Lateral Sclerosis

Advantages of Complementary Stereo Images as Viewed with the Low-Temperature Field-Emission SEM

1992 ◽  
Vol 50 (2) ◽  
pp. 1314-1315
Author(s):  
William P. Wergin ◽  
Eric F. Erbe
Keyword(s):  
Fold Increase ◽  
Horizontal Displacement ◽  
Three Dimensions ◽  
Stereo Image ◽  
Stereo Pair ◽  
Sem Micrograph ◽  
Left And Right ◽  
The Common ◽  
The Brain ◽  
Pair Analysis

The eye-brain complex allows those of us with normal vision to perceive and evaluate our surroundings in three-dimensions (3-D). The principle factor that makes this possible is parallax - the horizontal displacement of objects that results from the independent views that the left and right eyes detect and simultaneously transmit to the brain for superimposition. The common SEM micrograph is a 2-D representation of a 3-D specimen. Depriving the brain of the 3-D view can lead to erroneous conclusions about the relative sizes, positions and convergence of structures within a specimen. In addition, Walter has suggested that the stereo image contains information equivalent to a two-fold increase in magnification over that found in a 2-D image. Because of these factors, stereo pair analysis should be routinely employed when studying specimens.Imaging complementary faces of a fractured specimen is a second method by which the topography of a specimen can be more accurately evaluated.

Sign in / Sign up

Export Citation Format

Share Document