Pulsed laser light forces cancer cells to absorb anticancer drugs--the role of water in nanomedicine.

Anticancer drugs executing their function intracellularly enter cancer cells via diffusive processes. Complementary to these slow processes, cells can be forced to incorporate drugs by convection - a more efficient transport process. Transmembrane convection is induced by moderately intense pulsed laser light (or light emitting diodes) changing the structure of nanoscopic water layers in cells. This is a fundamental difference with the method of photodynamic therapy. In a model system we demonstrate that a total irradiation time of one minute is sufficient to completely inhibit proliferation of cancer cells. Transmembrane convection protects healthy cells from extended chemotherapy exposure, could be exploited to overcome multidrug resistance, and is a promising new tool in a variety of therapies as well as in skin rejuvenation.

Tutankhamun's Antimalarial Drug for Covid-19.

Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. Current efforts to treat Covid-19 are based on this strategy. The first drugs used in patients infected with SARS-CoV-2 were antimalarial drugs. It is their mechanism of action, i. e., rise in endosomal pH, which recommends them against the new coronavirus. Disregarding their side effects, the study of their antiviral activity provides valuable hints for the choice and design of drugs against SARS-CoV-2. One prominent drug candidate is thymoquinone, an antimalarial substance contained in Nigella sativa - most likely one of the first antimalarial drugs in human history. Since the outbreak of the pandemic, the number of articles relating thymoquinone to Covid-19 continuously increases. Here, we use it as an exemplary model drug, compare its antiviral mechanism with that of conventional antimalarial drugs and establish an irreducible parametric scheme for the identification of drugs with a potential in Covid-19.Translation into the laboratory is simple. Starting with the discovery of Nigella sativa seeds in the tomb of Pharaoh Tutankhamun, we establish a physicochemical model for the interaction of thymoquinone with both coronavirus and cells. Exploiting the predictive capability of the model, we provide a generalizable scheme for the systematic choice and design of drugs for Covid-19. An unexpected offshoot of our research is that Tutankhamun could not have died of malaria, a finding contrary to the mainstream theory.

Quantum biology in low level light therapy: death of a dogma.

BACKGROUND: It is shown that despite exponential increase in the number of clinically exciting results in low level light therapy (LLLT), scientific progress in the field is retarded by a wrong fundamental model employed to explain the photon-cell interaction as well as by an inadequate terminology. This is reflected by a methodological stagnation in LLLT, persisting since 1985. The choice of the topics is, by necessity, somewhat arbitrary. Obviously, we are writing more about the fields we know more about. In some cases, there are obvious objective reasons for the choice. Progress in LLLT is currently realized by a trial and error process, as opposed to a systematic approach based on a valid photon-cell interaction model. METHODS: The strategy to overcome the current problem consists in a comprehensive analysis of the theoretical foundation of LLLT, and if necessary, by introducing new interaction models and checking their validity on the basis of the two pillars of scientific advance (I) agreement with experiment and (II) predictive capability. The list of references used in this work, does contain a representative part of what has been done in the photon-cell interaction theory in recent years, considered as ascertained by the scientific community. RESULTS: Despite the immense literature on the involvement of cytochrome c oxidase (COX) in LLLT, the assumption that COX is the main mitochondrial photoacceptor for R-NIR photons no longer can be counted as part of the theoretical framework proper, at least not after we have addressed the misleading points in the literature. Here, we report the discovery of a coupled system in mitochondria whose working principle corresponds to that of field-effect transistor (FET). The functional interplay of cytochrome c (emitter) and COX (drain) with a nanoscopic interfacial water layer (gate) between the two enzymes forms a biological FET in which the gate is controlled by R-NIR photons. By reducing the viscosity of the nanoscopic interfacial water layers within and around the mitochondrial rotary motor in oxidatively stressed cells R-NIR light promotes the synthesis of extra adenosine triphosphate (ATP). CONCLUSIONS: Based on the results of our own work and a review of the published literature, we present the effect of R-NIR photons on nanoscopic interfacial water layers in mitochondria and cells as a novel understanding of the biomedical effects R-NIR light. The novel paradigm is in radical contrast to the theory that COX is the main absorber for R-NIR photons and responsible for the increase in ATP synthesis, a dogma propagated for more than 20 years.

Alternative Reaction Channels and Carbene Intermediates in the Ce4+-Malonic Acid and Ce4+-Bromomalonic Acid Reactions. 1. CO2 Measurements.

The Ce4+-malonic/bromomalonic acid reactions play an important role in the oscillatory Belousov-Zhabotinsky reaction. In this work CO2 evolution from these reactions was studied with a sensitive and quantitative method, by converting the CO2 to methane and measuring it with a flame ionization detector. It was found that the stoichiometries depend on the initial conditions in batch experiments or on the mixing rate of reagents in a semibatch reactor. These findings are explained by two main reaction channels: one for recombination and another for decarboxylation. Decarboxylation itself has two separate routes, one is dominant at low while the other at high Ce4+ concentrations. In the latter, formation of more than two CO2 molecules from one malonic/bromomalonic acid molecule was observed. Novel reaction schemes containing carbenes are proposed for these "high Ce4+" decarboxylation channels. To check the new mechanism, HPLC measurements are planned as a continuation of the research.

Involutes: the geometry of chemical waves rotating in annular membranes.

According to earlier theories certain parts of a chemical wave front propagating in a 2-D excitable medium with a convex obstacle should be involutes of that obstacle. The present paper discusses a special case where self-sustained chemical waves are rotating around a central obstacle in an annular 2-D excitable region. A simple geometrical model of wave propagation based on the Fermat principle (minimum propagation time) is suggested. Applying this model it is shown that the wave fronts in the case of an annular excitable region should be purely involutes of the central obstacle in the asymptotic state. This theory is supported by experiments in a novel membrane reactor where a catalyst of the Belousov-Zhabotinsky reaction is fixed on a porous membrane combined with a gel medium. Involutes of circular and triangular obstacles are observed experimentally. Deviations from the ideal involute geometry are explained by inhomogeneities in the membrane. (c) 1995 American Institute of Physics.

Waves of excitation on nonuniform membrane rings, caustics, and reverse involutes.

Chemical wave experiments on concentric nonuniform membrane rings are presented together with their theoretical description. A new technique is applied to create a slow inner and a fast outer zone in an annular membrane. An abrupt qualitative change of the wave profile was observed while decreasing the wave velocity in the inner zone. This phenomenon and all the experimental wave profiles can be adequately described by assuming that waves are involutes of a relevant caustic. A possible connection with recent models of atrial flutter is also set forth. (c) 1997 American Institute of Physics.

Polyreactive antibodies in multidonor-derived immunoglobulin G: theory and conclusions drawn from experiments.

Multidonor-derived (md) preparations of IgG antibodies, agents of therapeutic potential, contain molecules interacting at clonal concentrations (concns) and with affinities recently estimated to cover a considerable range. Here we demonstrate that polyreactivity of the monomeric molecules represents the essential driving force of formation of the main reaction product, the IgG-dimers. This conclusion is obtained by applying the principles of the law of mass action to dimer formation by polyreactive monomeric reactants. In addition, general interrelationships involving the mean number of reactants per reactor, the experimental dimer portion (w/w) and the mean concentrations of monomers in a polyreactive and monoreactive antibody system are derived. These interrelationships, together with quantitative results obtained from simplified computational kinetic models of polyreactive antibodies, allow to estimate a remarkably high value for the mean number of reactants per reactor, exceeding 60 for the underlying IgG preparation obtained from pooled human plasma units of 5000 donors. Moreover, the potential origin and other consequences of polyreactivity are outlined.

Contribution to the chemistry of the Belousov-Zhabotinsky reaction. Products of the Ferriin-Bromomalonic acid and the Ferriin-Malonic acid reactions.

In the present mechanistic schemes of the ferroin-catalyzed oscillatory Belousov-Zhabotinsky (BZ) reaction the oxidation of the organic substrates (bromomalonic or malonic acid) by ferriin (the oxidized form of the catalyst) plays an important role. As the organic products of these reactions were not yet identified experimentally, they were studied here by an HPLC technique. It was found that the main organic oxidation product of bromomalonic acid is bromo-ethene-tricarboxylic acid (BrEETRA), the same compound that is formed when bromomalonic acid is oxidized by Ce4+ (another catalyst of the BZ reaction). Formation of BrEETRA is explained here by a new mechanism that is more realistic than the one suggested earlier. To find any oxidation product of malonic acid in the ferriin-malonic acid reaction was not successful, however. Neither ethane-tetracarboxylic acid (ETA) nor malonyl malonate (MAMA), the usual products of the Ce4+- malonic acid reaction, nor any other organic acid, not even CO2, was found as a product of the reaction. We propose that malonic acid is not oxidized in the ferriin-malonic acid reaction, and it plays only the role of a complex forming catalyst in a process where Fe3+ oxidizes mostly its phenantroline ligand.