Massimo Pregnolato
University of Pavia, Drug Sciences, Faculty Member
Efavirenz (EFV, DMP-266) is a new antiretroviral agent belonging to the class of nonnucleoside reverse transcriptase inhibitors. It has recently been approved by the Food and Drug Administration in management of human immunodeficiency... more
Efavirenz (EFV, DMP-266) is a new antiretroviral agent belonging to the class of nonnucleoside reverse transcriptase inhibitors. It has recently been approved by the Food and Drug Administration in management of human immunodeficiency virus (HIV). Preliminary pharmacokinetic studies on EFV in healthy volunteers show that the drug may influence the metabolism of protease inhibitors. For the determination of EFV in human plasma, a validated and specific reverse-phase high-performance liquid chromatography (HPLC) method, with UV detection, was developed. We used 100 microL plasma sample for a liquid-liquid extraction with diethyl ether after basification. The mobile phase was a mixture of acetonitrile and water, pumped at a flow rate of 1.2 mL/min. Ultraviolet detection was carried out at a wavelength of 247 nm. Retention times for EFV and internal standard (IS) were 5.3 and 4.5 minutes, respectively, and there was no chromatographic interference from other commonly administered drugs. The limit of detection was 100 ng/mL. The described assay is a rapid and accurate method for measurement of EFV in plasma: the easy preparation and small sample size makes this assay highly suitable for pharmacokinetic studies and routine clinical analysis in patients with HIV. In addition, the reproducibility of the method is only moderately increased by including IS, so analyzing without IS may be an alternative.
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ABSTRACT Disseminated infections with Mycobacterium tuberculosis (MT) and Mycobacterium avium complex (MAC) are increasingly opportunistic diseases in patients with advanced acquired human immunodeficiency syndrome (AIDS). A series of... more
ABSTRACT Disseminated infections with Mycobacterium tuberculosis (MT) and Mycobacterium avium complex (MAC) are increasingly opportunistic diseases in patients with advanced acquired human immunodeficiency syndrome (AIDS). A series of N-alkyl-1, 2-dihydro-2-thioxo-3-pyridinecarbothioamides has been synthesized, and MICs for MT and MAC strains, either standard or isolated from infected patients, have been determined. Preliminary tests show a good activity and a very low toxicity for some derivatives. Pharmacokinetic studies in the rat show a very rapid elimination from the body after intravenous administration and a poor absorption after oral administration.
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Research Interests: Engineering, Biochemistry, Biophysics, Chemistry, Medicine, and 13 moreBiological Sciences, Temperature, Glycosylation, CHEMICAL SCIENCES, Bacillus subtilis, Time Factors, Pyrimidine, Recombinant Proteins, Hydrogen-Ion Concentration, Biomacromolecules, Sepharose, Purine Nucleoside Phosphorylase, and Deoxyuridine.
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Research Interests: Chemistry and Hydrocarbon
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The crude porcine pancreas lipase (PPL) extract is a mixture of several proteins (mainly lipases and esterases). In order to develop enzymatic catalysts with good catalytic properties for hydrolytic enantioselective reactions in aqueous... more
The crude porcine pancreas lipase (PPL) extract is a mixture of several proteins (mainly lipases and esterases). In order to develop enzymatic catalysts with good catalytic properties for hydrolytic enantioselective reactions in aqueous homogeneous medium, we studied the immobilization of the different enzymes contained in the crude PPL extracts by selective sequential adsorption on hydrophobic supports bearing octyl, octadecyl and
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Research Interests: Chemistry and Nucleotide
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The antimicrobial properties of N-(2-hydroxyethyl)-1,2-benzisothiazol-3(2H)-thione (1a,b) and its carbamic esters 2a,b-6a,b were tested in vitro against Gram positive and Gram negative bacteria, yeasts and dermatophytes. All compounds... more
The antimicrobial properties of N-(2-hydroxyethyl)-1,2-benzisothiazol-3(2H)-thione (1a,b) and its carbamic esters 2a,b-6a,b were tested in vitro against Gram positive and Gram negative bacteria, yeasts and dermatophytes. All compounds markedly inhibit the growth of Gram positive bacteria exhibiting MIC values ranging from 1.25 to 10 micrograms/ml. A strong antifungal activity is exerted against dermatophytes with MICs, in general, between 0.7 and 12 micrograms/ml. Structure-activity relationship studies show that these compounds are, in most cases, more effective than the corresponding benzisothiazolone analogues 7-12. None of the tested compounds shows genotoxic properties by Bacillus subtilis rec-assay and Salmonella-microsome test.
Research Interests: Chemistry, Medical Microbiology, DNA damage, Medicine, DNA, and 15 moreGram Positive, Antimicrobial activity, Bacteria, Antifungal Activity, Antimicrobial, Gram Positive Bacteria, Gram-negative bacteria, Anti-Bacterial Agents, Bacillus subtilis, Microbial Sensitivity Tests, Thiazoles, Structure activity Relationship, Carbamates, Mutagenicity tests, and Pharmacology and pharmaceutical sciences
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We describe the binding between the glycoprotein Spike of SARS-CoV-2 and the human host cell receptor ACE2 as a quantum circuit, comprising the one-qubit Hadamard quantum logic gate performing the quantum superposition of the S1 subunit... more
We describe the binding between the glycoprotein Spike of SARS-CoV-2 and the human host cell receptor ACE2 as a quantum circuit, comprising the one-qubit Hadamard quantum logic gate performing the quantum superposition of the S1 subunit of the spike protein, and the two-qubit quantum logic gate CNOT, which performs maximum entanglement between the spike-qubit S1 and the ACE2 receptor protein. Also, we consider two strategies to prevent the binding process between the spike-qubit S1 and the ACE2 receptor. The first one is the use of competitive peptidomimetic inhibitors that can selectively bind to the receptor binding domain (RBD) of the Spike glycoprotein with much higher affinities than the cell surface receptor itself. These inhibitors are targeted to the CNOT quantum logic gate and will get maximally entangled with the S1 qubit in place of the natural ACE2 receptor. The second one is to use covalent inhibitors, which will destroy S1 by acting as a projective quantum measurement....
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In this paper we consider the results obtained by biochemical experimental data on platelet membrane fatty acids processed by a Self Organizing Map (SOM) from apparently healthy, bi - polar (BD) and major depressive subjects (MDD). The... more
In this paper we consider the results obtained by biochemical experimental data on platelet membrane fatty acids processed by a Self Organizing Map (SOM) from apparently healthy, bi - polar (BD) and major depressive subjects (MDD). The SOM shows that major depressive subjects belong to an area which is completely disconnected from that of healthy and bi - polar. Looking at the location of the data over the SOM, we find also a region which we attribute t o psychotic subjects according to the clinical diagnosis. We translated these facts in terms of symmetry breaking, confirming that MDD is a disease completely trapped apart from healthy, bi - polar, and psychotic subjects.
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Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of... more
Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of these phenomena suggesting their involvement in chronic emotional patterns and in the pathology of cancer. Recent developments on biophysics, translational biology and psychoneuroendocrinoimmunology (PNEI) can support explanatory hypotheses about the link between emotional stresses and the origin and development of different types of tumor cells. Chronic stresses may cause perturbations of rhythms of the PNEI system, excessive activation of HPA axis and abnormal activation of calcium signals in somatic tissues, with deleterious effects on different parts of the body. The increasing of calcium signaling inside cells may lead to a deregulation of different pathways and epigenetic systems that promote the production of genomic mutations in a second pha...
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ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select... more
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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Quantum games have proposed a new point of view for the solution of the classical problems and dilemmas in game theory. It has been shown that are more efficient than classical games and provide a saturated upper bound for this efficiency... more
Quantum games have proposed a new point of view for the solution of the classical problems and dilemmas in game theory. It has been shown that are more efficient than classical games and provide a saturated upper bound for this efficiency [1]. Entanglement, when included in quantum games, makes (somehow) everybody win. Entangled quantum strategies are such that all players cooperate, and classical egoism (destructive) is replaced by quantum altruism (constructive) [2]. Entanglement might explain some form of telepathy, actually quantum pseudo-telepathy between “quantum-minded ” players who play a quantum game. Thanks to entanglement, perhaps the most nonclassical manifestation of quantum mechanics, two or more quantum players can accomplish a distributed task with no need for communication whatsoever, which would be an impossible feat for classical players. Einstein, Bohr, Bell, Kochen and Specker were all concerned with hidden variables (“elements of reality”). Pseudo-telepathy als...
We introduce a quantum logic for quantum information, which we identify with the quantum logic of the psychodynamic unconscious, amenable to formal characterization through the theoretical framework of Quantum Mind. We claim that this sub... more
We introduce a quantum logic for quantum information, which we identify with the quantum logic of the psychodynamic unconscious, amenable to formal characterization through the theoretical framework of Quantum Mind. We claim that this sub rosa quantum logic of the normal mind’s unconscious domain is also the dominant, pathologically emerging logic of schizophrenia. We interpret Quantum Meta-language as speaking as a quantum control about such a quantum logic. We then suggest that psychotherapists might learn this formal Quantum Meta-language and apply it in practice in order to communicate more easily with schizophrenic patients.
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One of the main clinical signs of irreversible human death is the flat EEG. It means that in this condition neurons do not generate action potentials, and therefore cannot control body movement and vital physiological functions. However,... more
One of the main clinical signs of irreversible human death is the flat EEG. It means that in this condition neurons do not generate action potentials, and therefore cannot control body movement and vital physiological functions. However, after brain death, the rate of destruction of cerebral and other cells is different in the several body districts. We consider at least two approaches to the physical correlates of quantum consciousness in that condition. The first one is related to quantum effects in proteins, which can maintain unchanged their folding and water environment in several cells after brain death. The second one considers a part of conscious activity related to the formation of potentials in electrolyte systems containing water, ions and proteins, which can maintain charges (difference of potentials) after brain death. In the first approach the Schrodinger proteins can be considered the basis of quantum information; therefore, quantum consciousness may remain until the...
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The consciousness is the basis of our reality and our existence, but the mechanism by which the brain generates thoughts and feelings remains unknown. Most of the explanations depict the brain as a computer, with nerve cells (neurons) and... more
The consciousness is the basis of our reality and our existence, but the mechanism by which the brain generates thoughts and feelings remains unknown. Most of the explanations depict the brain as a computer, with nerve cells (neurons) and their synaptic connections acting as simple switches. However, the calculation alone cannot explain why we have feelings, awareness and "inner life". Indeed, neurophysiological processes and phenomena of the mind are now among the biggest unanswered questions in science. It is time for quantum consciousness.
Research Interests: Psychology, Consciousness, Mind, Key words, Thought, and 5 moreMechanism, Reality, Feeling, Quantum Consciousness, and Computer
Contemporary theories of consciousness are based on widely different concepts of its nature, most or all of which probably embody aspects of the truth about it. Starting with a concept of consciousness indicated by the phrase "... more
Contemporary theories of consciousness are based on widely different concepts of its nature, most or all of which probably embody aspects of the truth about it. Starting with a concept of consciousness indicated by the phrase " the feeling of what happens " (the title of a book by Antonio Damásio), we attempt to build a framework capable of supporting and resolving divergent views. We picture consciousness in terms of Reality experiencing itself from the perspective of cognitive agents. Each conscious experience is regarded as composed of momentary feeling events that are combined by recognition and evaluation into extended conscious episodes that bind cognitive contents with a wide range of apparent durations (0.1 secs to 2 or more secs, for us humans, depending on circumstances and context). Three necessary conditions for the existence of consciousness are identified: a) a ground of Reality, envisaged as an universal field of potentiality encompassing all possible manifestations, whether material or 'mental'; b) a transitional zone, leading to; c) a manifest world with its fundamental divisions into material, 'informational' and quale-endowed aspects. We explore ideas about the nature of these necessary conditions, how they may relate to one another and whether our suggestions have empirical implications.
Research Interests: Psychology, Emotion, Ontology, Epistemology, Metaphysics of Consciousness, and 15 moreMetaphysics of Time, Alfred North Whitehead, Consciousness, Metaphysics of Mind, Extended Mind, Panpsychism, Neutral monism, Consciousness Studies, Philosphy of mind, Experience, Philosophy of the Subject, Process and Reality, Nonreductive Physicalism, Dual Aspect Monism, and Panprotopsychism
We give a short review of the most recent work done on the logical structure of the mind and on the peculiar logical aspects of some mental diseases like schizophrenia and major depression. Then, we illustrate the computational aspects... more
We give a short review of the most recent work done on the logical structure of the mind and on the peculiar logical aspects of some mental diseases like schizophrenia and major depression. Then, we illustrate the computational aspects and the physical interpretation of such logical structures. In this context, we also consider a quite important feature of the mind, namely its non-Turing-computable side. The latter is responsible for the fundamental difference between a human mind and a computer, classical or quantum whatsoever.
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Discussion: The Platonic Academy was banished by the Byzantine emperor Justinian the Great in 529 AD. The traditional story of its re-establishment near Florence during the 15 Century became legendary. The story centers around Cosimo de... more
Discussion: The Platonic Academy was banished by the Byzantine emperor Justinian the Great in 529 AD. The traditional story of its re-establishment near Florence during the 15 Century became legendary. The story centers around Cosimo de Medici when he attended the Council of Florence in 1438, where he became intrigued by the pagan philosophies of Plato, as expounded by the philosopher Gemistus Pletho. Cosimo intended to re-establish the Platonic Academy near Florence and finally achieved this goal in 1462 (Hankins J. 1990). Years prior to the opening Marsilio Ficino, having demonstrated youthful enthusiasm toward Platonic spiritual philosophy, was taught Greek and was carefully groomed to guide the academic functioning of the Academy. Cosimo, his son and grandson, provided Ficino with a residence in Caregina, central to the new Academy, to develop the lost atomistic spiritual tradition of Platonic philosophy. Ficino based his Renaissance upon Platonic theology (Snyder J. 2012).
Research Interests: Art and Transhumanism
To analyze cortico-cortical interactions in different consciousness states, namely during NREM sleep and wakefulness, we compared evoked potentials from 5 mA intra-cerebral stimulations in an epileptic subject undergoing clinical... more
To analyze cortico-cortical interactions in different consciousness states, namely during NREM sleep and wakefulness, we compared evoked potentials from 5 mA intra-cerebral stimulations in an epileptic subject undergoing clinical evaluation. We collected recordings from 16 different cortical areas and analyzed the perturbation effects in a 200ms time range after the stimulus using both cross-Coherence and Granger causality and comparing the two procedures. Results show that the overall interaction intensity involves a wider frequency range during wakefulness than during NREM sleep. Moreover, comparing similar Coherence intensity thresholds, the number of interacting areas is sharply higher during wakefulness. However, during the NREM phase, interactions show a highly directional behavior that is not present during wakefulness. The study displays which areas are mainly involved in reciprocal Gcausal interactions, paving the way to a following research on their functional meaning. Key...
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The present work aims to examine the worrying problem of antibiotic resistance and the emergence of multidrug-resistant bacterial strains, which have now become really common in hospitals and risk hindering the global control of... more
The present work aims to examine the worrying problem of antibiotic resistance and the emergence of multidrug-resistant bacterial strains, which have now become really common in hospitals and risk hindering the global control of infectious diseases. After a careful examination of these phenomena and multiple mechanisms that make certain bacteria resistant to specific antibiotics that were originally effective in the treatment of infections caused by the same pathogens, possible strategies to stem antibiotic resistance are analyzed. This paper, therefore, focuses on the most promising new chemical compounds in the current pipeline active against multidrug-resistant organisms that are innovative compared to traditional antibiotics: Firstly, the main antibacterial agents in clinical development (Phase III) from 2017 to 2020 are listed (with special attention on the treatment of infections caused by the pathogens Neisseria gonorrhoeae, including multidrug-resistant isolates, and Clostri...
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In this paper, we describe the development of an efficient enzyme immobilization procedure based on the activation of epoxy carriers with glucosamine. This approach aims at both creating a hydrophilic microenvironment surrounding the... more
In this paper, we describe the development of an efficient enzyme immobilization procedure based on the activation of epoxy carriers with glucosamine. This approach aims at both creating a hydrophilic microenvironment surrounding the biocatalyst and introducing a spacer bearing an aldehyde group for covalent attachment. First, the immobilization study was carried out using penicillin G acylase (PGA) from Escherichia coli as a model enzyme. PGA immobilized on glucosamine activated supports has been compared with enzyme derivatives obtained by direct immobilization on the same non-modified carriers, in the synthesis of different 3′-functionalized cephalosporins. The derivatives prepared by immobilization of PGA on the glucosamine-carriers performed better than those prepared using the unmodified carriers (i.e., 90% versus 79% cefazolin conversion). The same immobilization method has been then applied to the immobilization of two other hydrolases (neutral protease from Bacillus subtili...
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The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with... more
The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with the distance from the generating structure, vanishing at very short distances. This makes very hard their detection using standard experimental methods. However, the existence of fast-moving charged particles in the macromolecules inside both intracellular and extracellular fluids may envisage the generation of localized electric currents as well as the presence of closed loops, which implies the existence of magnetic fields. Moreover, the whole set of oscillatory frequencies of various substances, enzymes, cell membranes, nucleic acids, bioelectrical phenomena generated by the electrical rhythm of coherent groups of cells, cell-to-cell communication among population of host bacteria, forms the increasingly complex hierarchies of electromagnetic signals of different frequencies which cover the living being and represent a fundamental information network controlling the cell metabolism. From this approach emerges the concept of electromagnetic homeostasis: that is, the capability of the human body to maintain the balance of highly complex electromagnetic interactions within, in spite of the external electromagnetic noisy environment. This concept may have an important impact on the actual definitions of heal and disease.
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This paper focuses on the relationship between platelets and neurons by relating the membrane viscosity with the concentrations of the neurotransmitter serotonin. The action of serotonin being mediated by the platelet membrane arachidonic... more
This paper focuses on the relationship between platelets and neurons by relating the membrane viscosity with the concentrations of the neurotransmitter serotonin. The action of serotonin being mediated by the platelet membrane arachidonic acid concentration and by its exchange with the neuron membrane in the brain. The hypothesis that some diseases such as scleroderma and inflammatory bowel syndrome develop in relation to pathological features of cerebral and enteric neurons, in coexistence of depressive disorders, is here considered. In this context, depression is seen as the original structure of our existence in the world, both from a biological point of view that existential
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The QPP conference in Palermo has marked a definite turning point in the foundational perspective of many of the group’s participants regarding the study of psychopathology, particularly mood disorders. One reason for this turning point... more
The QPP conference in Palermo has marked a definite turning point in the foundational perspective of many of the group’s participants regarding the study of psychopathology, particularly mood disorders. One reason for this turning point stems from a realization that two of the most common forms of psychopathology, major depression and bipolar disorder, may be recognizable by means of biomolecular markers. Long years of theoretical study by independent investigators have finally culminated in a convergence of their insights via quantum paradigms that now promise to illuminate, through the empirically tangible route of such new biomolecular markers, pathological phenomena of the conscious brain, thus potentially both confirming in fact and further harmonizing the diverse prior contributions of these conceptually innovative psychiatrists, biochemists, molecular biologists, philosophers and theologians.
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Biology and culture, consciousness and the world, subject and object, inner and outer have continuity and find, in the "creative transcendence” of consciousness and its experiences, a privileged degree of understanding. This paper... more
Biology and culture, consciousness and the world, subject and object, inner and outer have continuity and find, in the "creative transcendence” of consciousness and its experiences, a privileged degree of understanding. This paper aims to show: 1) The validity of the phenomenological approach to consciousness and the subsequent interpretation of memory, expression of the “ego” as a continuous narrative of “self”, which persists even in the face of minimal consciential conditions, perhaps, even including traumatic brain injuries, justified on the bio molecular level, with the hypothesis that Schrödinger proteins (i.e. tubulins) are the biological interface from quantum to classical computation into quantum/classical consciousness processes and at the crossroad of memories and learning capacities. 2) That a molecular structure, such as tubulin, can effectively modulate the state of consciousness through the changes that occur within it. 3) A plausible hypothesis about the existan...