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¿Ibuprofeno o aspirina……..
en el tratamiento de la TB?
www.unitatdetuberculosiexperimental.wordpress.com
?
(x10 of the real size)
THE QUESTION
THE ANSWER:
because of the Coalescence theory
Because Laennec said it (XIX)….and we have seen it.
HOW DO WE KNOW?
because of the model
C3HeB/FeJ !!!
HOW DO WE KNOW?
because of the model
Marzo et al, Tuberculosis 2013; http://dx.doi.org/10.1016/j.tube.2013.09.004
THE COALESCENCE THEORY
0,5 mm Ø, d21
2 mm Ø, d301 mm Ø, d28
(x10 of the real size)
8 mm Ø, d33
HOW DO WE KNOW?
because of the model
Marzo et al, Tuberculosis 2013;
http://dx.doi.org/10.1016/j.tube.2013.09.004
Necrosed neutrophils
d21 d28
intraalveolar
acellular product
Big lesions
Central necrosis
Caseous necrosis
towards
liquefactive
necrosis
Bacilli in the
neutrophilic regions
…and in the
necrotised regions
Neutrophils
TB IS DUE TO A FIBROSIS-
ANTIFIBROSIS IMBALANCE
TB IS DUE TO A
FIBROSIS-ANTIFIBROSIS IMBALANCE
HEPARIN WORKS NOT BECAUSE ITS EFFECT ON
FIBROSIS BUT FOR IS ANTI-INFLAMMATORY
EFFECT
Bleomycin: induces fibrosis
Doxycyclin: inhibits MMP (involved in collagen degradation)
Heparin: antifibrotic effect
THE ORIGIN OF THE IDEA
ACTIVE TB IS AN INFLAMMATORY DISEASE
LET’S TRY ANTI-INFLAMMATORIES
WHICH ONES??
THE RESULTS
Control Ibuprofen
THE RESULTS
Vilaplana et al, Journal of Infectious Diseases 2013; doi: 10.1093/infdis/jit152)
LUNG PATHOLOGY BACILLARY LOAD SURVIVAL
pro-inflammatory mediators: TNF-α, IL-17, IL-6 and CXCL5
Marzo et al, Tuberculosis 2013 http://dx.doi.org/10.1016/j.tube.2013.09.004
THE RESULTS
0.5 mm Ø, d21
2 mm Ø, d301 mm Ø, d28
8 mm Ø, d33
THE WAY WE DO THINK IT WORKS
EncapsulationEncapsulationEncapsulationEncapsulation
0.5 mm Ø, d21
1 mm Ø, d28
0.5 mm Ø, d33
THE WAY WE DO THINK IT WORKS
Common anti-inflammatories are:
CHEAP ALREADY IN THE MARKETSAFEWIDELY AVAILABLE (WHO essential medicines)
WHY IS THIS IMPORTANT FOR TB PATIENTS?
THEY ARE READY TO BE USED
These results in mice encourage to use them as a COADJUVANT together with standard anti-TB treatment. Its use should ameliorate both the disease course and its outcome.
NEXT STEPS
STUDY IN SPAIN
(UITB+SEPAR+UTE: MIQUEL SERVET)
STUDY IN MOZAMBIQUE + SOUTH AFRICA(CISM+PHRU+UTE: EDCTP)
STUDY IN ANGOLA(VHIR+UTE: ?)
You are very welcome to present your ideas and collaborations!
PLEASE THINK ABOUT IT
THE PEOPLE
www.unitatdetuberculosiexperimental.wordpress.com