Lesson 3 Flashcards
Definition of chirality
Property of an object which is non-superimposable with its mirror image
How can you classify racemic drug activity?
- One bioactive enantiomer (eutomer) while the other is inactive, less active or toxic (distomer)
- Two equally active enantiomers with the same pharmacodynamics
- There’s one eutomer and the distomer could be transformed in body into its bioactive antipode by chiral inversion
How can we define the toxicity of solids?
Solid are not solubilized in aqueous solutions and they’re not toxic at the first contact but with several exposures. The contact lasts for a really long time due to their persistent presence inside the organism.
Based on their dimension, they can enter the blood circulation and diffuse in the whole organism reaching the cell. Interaction of the solid surface with the living organism can induce proteins modifications. Solid are engulfed by macrophages and there are different cycles of cell death and phagocytosis before they can be cleared.
Why are abestos fibers toxic? (characteristics, not mechanism)
Their toxicity is due to:
- Fibre size
- Biopersistence
- Chemical composition
- Particle surface characteristics
With which mechanism asbestos fibers cause disease?
There are three hypotheses:
- Direct interaction with cellular chromosomes: asbestos can bind cellular macromolecules (proteins, DNA, RNA) and cell surface proteins inducing changes in conformations
- Release of reactive oxygen species: they may cause the formation of ROS in lungs. Macrophages try to engulf and digest the asbestos fibre and generate lysosomal contents in the alveolar space.
This kind of phagocytosis can generate ROS which induce TNF α (inflammatory cytokines which cause pulmonary fibrosis)
- Other cell-mediated mechanisms:
o Apoptosis
o Cell and DNA damage
o Cell proliferation
o Inflammation
o Macrophage recruitment
How can asbestos fibers be removed?
- Mucociliary clearance: the cleared material is swallowed and enters the GI tract or coughed out
- Alveolar macrophages: they phagocyte the asbestos particles. Sometimes, these particles may be toxic to the macrophages.
With increasing dimension phagocytosis becomes ineffective (frustrated phagocytosis)
Which disease may be due to the asbestos fibers?
Pleural mesothelioma
How is composed the urban particulate matter?
Coarse particles (larger size) penetrate no further than the bronchi as they’re filtered out in the nose and throat via cilia and mucus.
Fine particles are produced from various combustion sources (diesel engine, gasoline engine, biomass burning…) and non-combustion sources (ammonium sulfate, ammonium nitrate…).
They can penetrate in the bronchioles or alveoli.
Ultrafine particles may pass through the lungs to affect other organs
Which factors influence the penetration of the PM particles?
size, shape, chemical composition
Which are the effects of PM exposition?
- Asthma
- Lung cancer
- Respiratory diseases
- Cardiovascular diseases
- Premature delivery
- Birth defect
- Premature death
If you have to determine solid reactivity in a biological system, which factors do you have to consider?
- Absorption: the solid can absorb substances from the environment and endogenous substances in the organism. If the soldi particles is not toxic, it can become a vector of toxic particles.
- Ions release: once in the organism, the solid will contact an aqueous environment in which it can be solubilized. The more external ions go into the solution
- Solubilization: it depends on the chemical structure of the solid and it’s favoured by temperature and ion selective extraction process.
Which physical features should be consider in order to determine reactivity in a biological system?
There are some physical features which have to be known:
o Fibres: it’s the shape that penetrates more easily in tissues, they’re more difficult to be discarded and can lead to incomplete or frustrated phagocytosis
o Crystallinity: crystals are more toxic
o Surface irregularity: irregular surfaces are more extended and therefore they have more possibilities to interact with molecules.
Definition of biomineralization with examples
It’s a process by which living organisms produce minerals, often to harden or stiffen existing tissues (mineralized tissues).
