COVID-19-related complications and decompression illness share main features.: Could the SARS-CoV2-related complications rely on blood foaming?

A study by Saraiva et al. (2011) demonstrated the presence of Angiotensin II receptors on the erythrocyte membrane. This little-known information should be deemed as crucial as the SARS-CoV-2 relationships with oxygen saturation and the Renine Angiotensin System but it currently remains unexploited. The pulmonary and cardiovascular systems are involved in any typical complications of COVID-19 but numerous other unrelated symptoms may occur. To fill the gap, we shall first emphasize some similarities between the complications of this infectious disease and Decompression Illness (DCI), which involves bubble formation. We theorized that the Angiotensin II clearance by the red blood cells could trigger the release of its oxygen content in the bloodstream. The resulting foam would worsen the widespread endotheliitis, worsen the gas exchange, trigger the coagulation process, the inflammation process and the complement pathway as typically occurs in DCI. At the end, we propose a plausible mechanism.

Heuristic consequences of a load of oxygen in microtubules.

The current cell oxygen paradigm shows some major gaps that have not yet been resolved. Something seems to be lacking for the comprehensive statement of the oxygen distribution in the cell, especially the low cytoplasmic oxygen level. The entrapment of oxygen in microtubules (MTs) resolves the latter observation, as well as the occurrence of an extensive cytoplasmic foam formation. It leads to a novel oxygen paradigm for cells. During the steady-state treadmilling, the mobile cavity would absorb oxygenated cytoplasm forward, entrap gas nuclei and concentrate them. A fluorescence method is described to confirm the in vitro load of oxygen in MTs during their periodic growths and shrinkages. The latter operating mechanism is called the gas dynamic instability (GDI) of MTs. Several known biosystems could rest on the GDI. (1) The GTP-cap is linked with the gas meniscus encountered in a tube filled with gas. The GTP hydrolysis is linked to the conformational change of the GTPase domain according to the bubble pressure, and to the shaking of protofilaments with gas particles (soliton-like waves). (2) The GDI provides a free energy water pump because water molecules have to escape from MT pores when foam concentrates within the MT. Beside ATP hydrolysis in motor proteins, the GDI provides an additional driving force in intracellular transport of cargo. The water streams flowing from the MT through slits organize themselves as water layers between the cargo and the MT surface, and break ionic bridges. It makes the cargo glide over a water rail. (3) The GDI provides a universal motor for chromosome segregation because the depolymerization of kinetochorial MTs is expected to generate a strong cytoplasmic foam. Chromosomes are sucked up according to the pressure difference (or density difference) applied to opposite sides of the kinetochore, which is in agreement with Archimedes' principle of buoyancy. Non-kinetochorial MTs reabsorb foam during GDI. Last, the mitotic spindle is imagined as a gas recycler. (4) The luminal particles within MTs (called MIPs) are imagined as a foam organizer, the luminal proteins being part of the borders and edges of identical bubbles. (5) Last, volatile anesthetics could destabilize MTs through anesthetic-induced bubble nucleation between protofilaments, and therefore causing shear stress and the opening of MT. The load of oxygen in MTs might provide a major advance in this area of research.

Alzheimer's disease: a gas model. The NADPH oxidase-Nitric Oxide system as an antibubble biomachinery.

Alzheimer's disease (AD) is a neurodegenerative disease of unknown origin. The pathological lesions that define AD would be linked to the insidious accumulation of nitrogen, having invaded the brain interstitial fluid (ISF) from the blood via the physiological cycling pool of vascular glucose transporters (GLUT-1). According to this hypothesis, the nitrogen nanobubbles, being chemically inert and actually indestructible for human beings, can not escape from the ISF anymore. They would exert a huge and deleterious pressure against cellular components, especially in microglia and in astrocytes. They could enhance the existing cell oxygen anisotropy, which might enhance the natural bubble nucleation of O2-2O2 in cells or in mitochondria. Indeed, with the help of a new symbolic representation for gas nuclei in chemical reactions, the NADPH oxidase-NO system is identified for the first time, as an antibubble biomachinery, able to break O2-2O2 bubbles up as it releases superoxide O2-. Superoxide is considered as a quantum bubble, which collapses through the reactivity of the gaseous NO radical. Their combination in soluble peroxinitrite provides the change from one state of matter to another, avoiding any risk of a bubble enlargement, and finally avoiding the risk of enzyme crowding or of a bulk pressure variation. However, a bubble is expected to entrap Nitric Oxide (NO), which leads theoretically to a decrease in its bioavailability, and is expected to trigger a guanylyl-cyclase-mediated inflammatory cascade, that could explain the inflammation in AD. In vitro, any increase in the hydrostatic pressure has already been linked to the microtubule disorganization. The amyloid deposits, also known as senile plaques, would behave as a sponge toward ISF nitrogen; Aß is considered as a foam-stabilizing agent. By taking the shape of cerebral amyloid angiopathy, the amyloid could confine the nitrogen leak from the blood, and progressively insulate the Blood-Brain Barrier against the pollutant. All these theoretical features finally lead to the death of the neurons. The comprehensive statement of the theoretical pro-inflammatory action of inert gases is a real upheaval for the whole medicine.