Particles and the Circulatory System
Once they enter the body through the lungs or the digestive system, particles travel in the blood. There they can interact with red and white blood cells, proteins, enzymes and other blood components. That interaction is regulated by properties like physical adhesiveness, electrostatic forces, chemical affinity, covalent bonds, hydrogen bonds, van der Waals forces, etc. .
Resuming what is written in Chapter 1, at the end of the nineties, studying caval filtration (see appendix, Chapter 1), we had already observed that particles can transform fibrinogen, that is, the soluble glycoprotein factor I of the coagulation factors, into fibrin (factor la) (see Chapter 2) (Fig. 4.2).
In the majority of subjects, particles are carried by the bloodstream, following its destiny, that is, reaching any organ and tissue. As to particles, it is impossible to predict whether all particles are captured by tissues and organs or, if they are, when. In fact, analysing blood samples, particles can always be found, but we can’t tell whether they have just entered the bloodstream or they have been there for a long time.
Our studies on leukaemia and cryoglobulinaemia identified statistically meaningful quantities of micro- and nanosized foreign bodies in the blood of these patients (Figs. 4.3 and 4.4) .
Figure 4.2 Particle identified in a thrombus of a myocardial infarct and fibrin bundle. Ba-S particles (d) had fibrinogen transformed into a fibrin bundle (c) in a thrombus. Pb-CI-Cr-Ca-Cu (b) particles found in a coronary vessel affected by a myocardial infarct.
Figure 4.3 Particles in a patient's blood affected by leukaemia. The particles shown in the images have been identified in the blood of a subject with acute myeloid leukaemia. The steel-based particles (iron, chromium and nickel) are obviously of exogenous origin. The presence of relatively coarse particles is worth noting, which, due to their size, cannot have entered through the pulmonary alveoli but, with great probability, by ingestion. The calcium-based particles, on the other hand, are almost certainly of endogenous origin and are characteristic of several forms of cancer.
Figure 4.4 Particles in a patient's blood affected by cryoglobulinaemia. Simple (monoclonal) cryoglobulinaemia or type-1 cryoglobulinaemia consists of the presence in the serum of an isotype or sub-class of immunoglobulins (Igs), which precipitate reversibly below 37°C. It is one of many orphan diseases of unknown origin. However, in the cases we have been able to examine, the serum contained, as in this case, numerous non-biocompatible metallic inorganic particles. The patient was affected also by hepatitis C virus.
In both pathologies, leukaemia and cryoglobulinaemia, we found not only foreign bodies but also traces of their nano-bio-interaction.
There is a direct correlation between the presence of internalised foreign bodies and how blood reacts. The type of reaction depends mainly on the particle's size, its morphology, its chemistry, its free energy of surface and its superficial electrical charges.
Particles can also adhere to erythrocytes. When particles are numerous enough, they can cover a significant part of the red blood cells' external surface, thus hindering their ability to carry oxygen and carbon dioxide (Fig. 4.5).
Once, we had a chance to examine a tract of descending aorta affected by an aneurism and found a concentration of particles embedded in the wall, while the healthy portion of the artery was ‘clean’ (Fig. 4.6).
Figure 4.5 Red blood cells with particles. Most of the particles which enter the body are carried by the blood, where they can also interfere with red blood cells. One of the possibilities is to deform them, as can be seen in these photographs.
Figure 4.6 Aortic aneurysm. We have no evidence to demonstrate the responsibility of solid and inorganic particles in causing an aortic aneurysm. Our case history includes only one case and, therefore, is completely insufficient to affirm anything. The only thing we can say is that the wall of the aneurysmal aortic tract we analysed contained particles of clear external origin (a spherical particle of just under 3 pm in diameter is shown in a photograph), while the healthy tissue did not contain any particulate pollutants.
Having only one case available, we could not give an explanation to what we were observing, the question being whether the particles had somehow caused the aneurism, perhaps because, being solid and hard, they had scratched the intima, or had been attracted there by the already damaged tissue or the altered hydrodynamics of the blood. In our opinion, the former possibility is less probable, since, for hydrodynamics reasons, the blood flow speed close to the wall is very slow, in fact, close to zero, so the particles would be unlikely to physically harm the intima. It is also hard to believe that those particles could have had the time to exert a biological action on the arterial wall. In any case, the problem requires further research based on an appropriate series.
The Environment: Polluted Sites
It is a widely known notion that all inhabited areas and, in particular, those with industrial settlements are polluted.
The consequences of pollution are not always immediately visible, and one example among many may be the situation on the southeast coast of Australia devastated by fires between the end of 2019 and the beginning of 2020. Regardless of the serious ecological problems caused by the loss of such vast expanses of vegetation, the ashes will inevitably cause negative consequences on flora and fauna, starting from those of microscopic dimensions. Already a few weeks after the fires occurred, the ashes fallen into the water had caused the death of a large number of fish, but the particles are not unlikely to also interfere with the DNA. Therefore, the consequences will become clearly visible only over the years.
Some examples of these contaminations were studied is in a research project of nano-ecotoxicity called INESE by the Italian Institute of Technology of Italy [9-13].
In Chapter 3 we have already discussed the generation of a new pollution due to war and terrorism. The exposure of humans and animals to these new contaminants can be the cause of new symptoms and new pathologies, not infrequently in the form of syndromes, that is, of sets of different symptoms, many of which are not described or barely mentioned in medical texts because of their novelty.
By now, there are highly polluted territories all over the planet and, in fact, impossible to reclaim.
An example may be that of the so-called 'Terra del Fuochi’ (Land of Fires), a vast territory which extends over an area hard to circumscribe accurately between the Italian provinces of Naples and Caserta. In that area, industrial residues and waste of largely unknown quantity and nature coming not only from Italy are poured in every day for decades. In addition, huge quantities of waste are continually set on fire. As often happens almost everywhere, the problem has been long ignored and, in the same way, frequent cases of cancer, miscarriages and foetal malformations of humans and animals have been underestimated or ignored at all. Now, as was obviously to be expected, the pollutants have infiltrated the soil to an unknown depth and, in any case, a depth which probably varies from site to site, depending on the quantity and type of waste and the quality of the soil. Local aquifers have certainly not been spared.
Now, belatedly, money is being allocated to reclaim those territories. What has been done in certain circumstances is to dig a few metres deep in limited areas and move that soil to places where people are unaware of what they are receiving.
In fact, recovering those territories is impossible. As for aquifers, beyond more or less questionable techniques, it is essential to realise that rainwater which almost always enters the underlying aquifer passes through polluted soil, dragging pollutants with it.
Most people believe that there is always a solution for any problem, but unfortunately, this is not the case.
The Aerotoxic Syndrome
Nanopathology is a novel concept, a possible key to understanding new pathologies, new syndromes, such as the so-called aerotoxic syndrome, a set of symptoms which affect airline crews and sometimes even some passengers. The epiphenomenon which indicates the occurrence of the toxic event is what is described by those who participated in it as a smell of wet dog or dirty socks. Then, a light and not always visible cloud is released inside the aircraft cabin. Such an occurrence is known as 'fume event’ (Fig. 4.7) [15,16].
Figure 4.7 Fume event in an aircraft. The image shows the effect of a fume event inside an aircraft. A sort of smog is dispersed in the aircraft cabin. Figure courtesy of the Aerotoxic Association.
When these conditions occur, the crew may be no longer able to reason properly and carry out normal activities, which, as is evident, is particularly critical with regards to the pilots.
In these cases, emergency landings are used. In others, fortunately rare, accidents occur which remain officially unexplained.
Among a number of possible examples, on 25 October 2016, an accident happened to the British Airways A380 flying from San Francisco to London, which was diverted to Vancouver in an emergency, where 25 people, the crew and some passengers, were taken to the hospital for the umpteenth case of ‘fume event'.
In those events, immediately after landing, the crew and, in some cases, the passengers are transported to the hospital and generally discharged after short hospitalisations.
The symptoms they declare are confusion, balance difficulty, severe headache, cognitive difficulties and emotional changes (great restlessness and aggression), and skin irritation (particularly in the face and arms).
The problem becomes more and more serious for the cabin crew, who, unlike passengers whose exposure is only occasional, can suffer the phenomenon with a certain frequency. Thus, to the symptoms listed above, others are added: severe hair loss, insomnia, swollen eyes, poor eyesight with photophobia, extreme fatigue, slight hearing loss, palpitations, fluctuating blood pressure, muscle weakness with severe pain, sciatic pain, stiff neck, alcohol intolerance and fragrance intolerance - a set of symptoms which is partially similar to that of a multiple chemical sensitivity.
Unfortunately, unlike what rarely happens with other pathologies, thanks to homeostasis, these symptoms tend to worsen over time, so much so that the crew, less and less able to tolerate the environment inside the plane, quit the job, and some crew members whose cases we dealt with have become completely unable to lead a normal life.
In the silence of both media and airlines, some pilots reported that their colleagues died from the aggravation of the symptoms. Nothing is known, however, of intoxicated passengers. It is possible that, having been victims only once of the event, they recovered perfectly as it is equally possible that their symptoms remained or even worsened without the doctors to whom they turned being able to find an explanation.
Without going into technical details which do not fall within our competences and the purposes of this book, an explanation of the phenomenon which, however one wants to deal with it, is real and repeats itself, despite attempts to minimise its scope, it must be considered that the air which is introduced into the cockpit of some models of aircraft passes through the engines, where it is compressed and heated .
For a number of reasons (malfunctioning, wear, age, etc.), that air may contain organic and inorganic pollutants coming from the lubricant: carbon monoxide and carbonaceous combusted particles, hydrogen cyanide, hydrogen fluoride, hydrogen chloride, nitrogen oxide, sulphur dioxide, ammonia, acrolein and combusted tricresylphoshate [17, 18]. As in the case of internal combustion engines in automobiles, also in this case solid and inorganic particles are formed by combustion.
At this point, it is necessary to take again into consideration a concept as basic as too often overlooked of toxicology: one plus one does not equal two. When two toxic substances are present together, except in rare cases, the sum of their toxicities is higher than that which would be obtained with a simple arithmetic addition of the two effects. When, as is the case we are dealing with, there are many pollutants involved, their combined effect is almost impossible to predict. What is certain is that it is much higher than what one might suppose by evaluating the substances
Figure 4.8 (a) Examples of pollution inside the oil to lubricate the engine. The particles shown in the photograph were identified in the lubricating oil of the engine, (b) Examples of particles dispersed in the aircraft. The particles are those captured by a filter placed at the entrance of the air into the cockpit environment of an airline. The compressed and heated air comes from the engines and is breathed by crew and passengers. Titanium and iron come from mechanical wear, while carbon, chlorine, potassium, sodium and sulphur come from pyrolysed oil.
individually. The problem is aggravated when the exposures are repeated, given the fact that those substances can accumulate in the body and can trigger states of sensitisation, even very serious ones. In view of this obviousness, minimisation attempts look naive to say the least, and the attempt to impose silence is the most certain means of not solving this like any other problem.
Not too rarely, what is put in place is the attitude of the majority of companies. So, if one faces the problem from a purely immediate economic and temporally limited point of view, it is understandable that after the fume event has occurred, the interior of the aircraft is not thoroughly cleaned, the oil is not changed and no overhaul is made of the air acquisition, treatment and delivery systems, including with this also the engines (Fig. 4.8).
Figure 4.9 Diseased pilot's fatty tissue. The particulate matter seen in the photographs was contained in the fatty tissue of an airplane pilot who had been forced to quit his job due to repeated exposure to smoke events. Similar particles, mainly composed of steel as they are, can probably come from the air introduced inside the cabin of the aircraft after passing through the engines. The particles seized in the fat can be released into the blood in the case of weight loss.
The hypothesis we conceived and which, free from understandable vested interests, seems reasonable to us is that the pathology is due to the inhalation of a mixture of gases, organic molecules and particulate dust composed of an inorganic core coated with organic compounds. So, the acute symptoms can be due to the mutual interaction of all toxic compounds in the blood circulation and in the brain, while the chronic symptoms can be due to the long-term presence of the inorganic ones in the organs and tissues, including also fat Fat can be of particular importance because, when it is consumed (and the fact is particularly visible in cases of rapid weight loss), the particles it contains are released within the organism to reach other tissues and organs.
We had the possibility to analyse some biological samples we got from ill patients or from their families if the patient had already died. The following images (Figs. 4.9 and 4.10) show part of these biological findings.
Figure 4.10 Dead pilot's brain. The particles shown in the images were detected in the brain of a deceased airplane pilot who suffered a series of fume events. The steel is most likely derived from the passage of the air which is introduced into the cabin of the aircraft after passing through the engines. Phosphorus-containing particles are likely to originate from the lubricant used in those engines.