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How Particles Behave in the BodyWe have already described in detail in our book Nanopathology: The Health Impact of Nanoparticles (Pan Stanford Publishing, 2008, now Jenny Stanford Publishing) how solid, inorganic micro- and nanoparticles which are insoluble in water and fats are generated. 
Figure 2.5 Micro- and nanosized foreign bodies detected inside a thrombus entrapped in a vena cava filter explanted from a patient who suffered from clotting disorders. In the three cases shown by electron microscopy images, it is clear how the particles which entered the blood, however they entered it, transformed the fibrinogen into fibrin, thereby constituting the scaffold for a thrombus. The elemental chemical analyses of the particles show different compositions (compounds of Fe-Cr-Ni, Pt, Sb-Co,) which have led to the same result, thereby demonstrating once again that by far the most relevant factor triggering the reaction is being a foreign body, regardless of other characteristics of the particles. 
Next we will concisely summarise the basic concepts. Their mass can be even millions of times smaller than that of a pollen, and therefore, particles float easily in the atmosphere, behaving in several ways as if they were a gas. For this reason, they are inhaled and breathed, being able to end up in the pulmonary alveoli, where they remain generally a few tens of seconds, negotiate the alveolar barrier and enter the bloodstream. Here, in a minority of subjects, those who do not have an efficient fibrinolytic system, the particles transform the soluble protein fibrinogen present in the plasma into the insoluble protein fibrin. Then, a thrombus forms on the fibrin bundle and that thrombus necessarily migrates to the pulmonary circulation if the phenomenon has occurred within the veins. The consequence is a pulmonary thrombo-embolism, a condition in which, depending on the vascular trunks which are occluded, one or more areas of the lungs are excluded and, if the area is large enough, death can be the result. In the event that the phenomenon occurs within the arteries, the embolising thrombus can end up in any body district, preventing the arrival of oxygenated blood to that particular tissue - hence, events such as myocardial infarction or stroke. 
Figure 2.6 Thrombus extracted from an infarcted coronary vessel. The electron microscopy images show three cases of thrombi removed by means of a thrombolyser from heart attack patients. All the thrombi contained foreign bodies surrounded by blood components. In this case there is a cluster of steel nanoparticles (white arrows). Their biointeraction triggered the transformation of fibrinogen into fibrin, thereby making up the scaffold for a thrombus. In the majority of subjects, though, if a thrombus has formed, it is immediately dissolved3 and the particles travel carried by the ^Fibrinolysis, the process of breaking down and dissolving a thrombus, is very quick in happening, mainly due to plasmin, the serine protease that, among other important functions, can degrade many blood plasma proteins, including fibrin clots. blood, virtually able to reach any organ or tissue, with destinations impossible to predict As soon as the particle reaches the end of its journey, the tissue where it has arrived behaves like any mechanical filter, capturing it. It is at this stage that the particles can be attacked by macrophages which incorporate them and take them elsewhere where they go to die, leaving organic residues which the body easily eliminates. The particle, however, is not degradable and remains where it was moved by the macrophage. The particles, be they where they ended after being moved by the macrophages or where the blood had brought them, according to a well-known mechanism of reaction to foreign bodies, are wrapped in a tissue (granulation tissue) which remains chronically inflamed and which, in times which can be very long, gives rise to cancer. In many circumstances, the time required for cancer to become clinically manifest is longer than the life of the individual and, therefore, the process goes unnoticed. To avoid misunderstandings, it is necessary to clarify that the type of cancer which is thus generated depends on many different factors, including the organ affected, its health, the quantity of particles involved, their shape, their size, their chemical constitution, their physical characteristics, the presence of any contributing causes, etc. As already mentioned, particles can penetrate inside the cells up to the nucleus, where they interfere in an unpredictable way with the DNA and take away h orn the cell the ability to repair itself and to resort to apoptosis as a last possibility of defense of the common good of all the cells of the organ involved and, ultimately, of the whole organism. Thus, the cell with the modified DNA reproduces, following incorrect instructions and, deprived of its ability to apoptosis, continues to reproduce erroneously as long as it is nourished. This event is that which makes the main difference between classical toxicology and nanotoxicology and it is the key to understanding many diseases of unknown origin, like cancer. But particles can also cause diseases which have nothing to do with cancer. Among these, is type 1 diabetes, in which particles, by reaching the pancreas, prevent beta cells of the islets of Langerhans from producing insulin. Reaching the brain, they can trigger behaviouralpathologies (e.g. aggressiveness, perhaps autism, Parkinson’s disease, Alzheimer’s disease, etc.). Going from the mother to the foetus without difficulty, they can cause abortions or malformations 
Figure 2.7 Case of a baby with cancer of the yolk sac. The images show the findings of particles within the yolk sac cancer in an infant. Particles of stainless steel (iron-chromium-nickel) have been detected, very common among urban polluting dust, and, together with those, copper-based particles of which we could not identify the origin. To do so, it would have been necessary to investigate at least the environment in which the mother (in an excellent health condition) lived, her activity, her diet and any medications she was taking. As is evident, micro- and nanoparticles can cause seemingly very different diseases. About 20 years ago, we grouped all those diseases by calling them nanopathologies, a name which, with its prefix ‘nano’, could lead to the error that these are diseases of little relevance. In fact, they are not only often very serious but also widespread. Not a few of them are still considered cryptogenic, that is, of unknown origin or of uncertain origin. The willingness to accept or, at least, to consider without obtusely refusing a priori possibilities other than the traditional ones could facilitate progress, leading to a better diagnostic capacity, more effective therapies and prevention strategies which avoid contracting the disease, that is, primary prevention, which, of all strategies, is the most effective and by far the least expensive. Objections to Particle TheoryOne of the most common objections to particle theory - as long as it’s actually a theory and not something objective observable by anyone who really wants to do it - is, ‘If dust is everywhere and is actually pathogenic, we should all get sick.' The objection is the same as the one advanced more than a century and a half ago against Pasteur: ‘If microbes are everywhere and they are actually pathogenic, we should all get sick.' Polymorphism is the main answer biology gives now to counter the objection as to microbes, that is, a phenomenon of differentiation of some DNA genes which, not for all people but for some of them, adapt by natural selection: a phenomenon subject to certain conditions, including the meeting between pathogens and the body, granting it the capacity to react defensively against the pathogens with the possibility of causing the disease. Then, account must be taken of how the body has a number of defense mechanisms grouped in its immune system. Those conditions may somehow apply to particles as well, but as much as we know now, there is no evidence. But the answer must also concern many other aspects of exposure to particles. Just to give some examples, nobody undergoes exactly the same exposure in terms of quantity, quality and exposure times. Admitting to having a group of never-exposed subjects and to letting them breathe the same quantity and quality of particles, each of them, according to the capabilities of their respiratory system, will exhale different quantities, and on the other hand, each of them will block different amounts in the lung alveoli. For example, smokers, with their underactive, when not altogether paralysed, vibritile cilia, and with the layer of mucus coating their airways, will be less able to get rid of the particles. In practical terms, such a simple situation as the one just hypothesised is in fact impossible, given that each of us has a different history of exposure, of course, not only to particles but to a huge number of poisons, and as is a well-known notion in toxicology, when numerous different toxic substances act simultaneously, the result is unpredictable and, in any case, is more serious than the arithmetic sum of the single effects. Another parameter to consider is the state of health of the subject and, in particular, of the target organ of the particles. In particular, a hyperemic organ because it is inflamed, just because it receives an excess of blood, has an increased chance of receiving particulate matter. Again by way of example, the particles can reach the brain by crossing the blood-brain barrier when, together with them, particular substances are present. These include, for example, glyphosate, a non-selective herbicide which pollutes many vegetable food products, and polysorbate80, an emulsifier currently used in vaccines: a type of combined exposure which takes place only occasionally. Ultimately, due to the great difference which exists between individuals and even in the same individual during his/her life up to variations which occur during the day, it is at least naive as well as being in contrast with the objectivity of science to expect that every man behaves exactly like his neighbour. Such a thing is possible with a very small margin of error only in unicellular beings. When reproduction is sexual with the meeting of different DNAs, as organisms grow more complex, the differences between individuals become more and more marked until they reach the maximum in Homo sapiens.This top of complexity exists not because we are biologically more complex than any primate but because, among other peculiarities, we have a psyche capable of interfering (chemically) with our physiology much more than it does in any other animal. Though we are aware of that, our current knowledge does not allow us to establish to what extent this peculiarity can affect micro-and nanoparticulate diseases. References
References I 31
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