The success of a pleiotropic integrated therapy against COVID-19

The success of a translational integrated therapy against COVID-19

Reading time: 9″

10.13140/RG.2.2.15071.12964/1

Giuseppe R.Brera*

A sixty years old unvaccinated woman, a great smoker, with a determinate temperament and basic trust, and a previous history of breast cancer with a swab positive diagnosis of COVID-19 developed a
temperature of 40 degrees, with headache and cough, an indicator of a high cytokine storm. She received an integrated therapy based on translational medicine structured on well-studied natural pleiotropic molecules
integrated with Nimesulide and Doxiciclin. The woman recovered from the severe COVID-19 syndrome in four days and joined the swab negativity in 10 days from the beginning of symptoms returning to work on the 11th day.

Article

  • Milan School of Medicine-Università Ambrosiana- Milano

 

Mass vaccination, the first time used to prevent a pandemic but with experimental mRNA and vectorial vaccines dangerous at the epigenetic-genetic level,[1] [2] [3] [4] and offered to the market with unreliable clinical research methods [5] [6] , and producing high rates of adverse effects and mortality, met in a minority of people also physicians and investigators a right diffidence and prudency to vaccinate people and themselves. These sera should have requested larger samples and a long time to be studied. The basic epistemological error caused by the lack of adoption in public health of the paradigm change of medical science and medicine, Person-Centered Medicine, must find an effective and cheap alternative allowing people primarily in countries with poor financial resources to prevent and care for viral and bacterial infections. To date, the deterministic-mechanistic paradigm used to cope with the pandemic implementing only biotechnology and profit is “Pathogen= mortality risk! and not the right indeterministic multidimensional one:” Pathogen-anti-pathogen allostasis = immunity-resilience- recovery”.[7] According to the Person-centered medicine primary prevention and therapy paradigm,clinical efforts must be addressed to improve life quality and psycho-biological resources to prevent and care for diseases and not to be problem-centered which improves only the disease-centered stock market. The World Health Charter should be adopted worldwide.

Anti-viral drugs and monoclonal antibodies are developed through fragmented research methods and show dangerous adverse effects while there are in nature pleiotropic, powerful and cheap molecules that, without adverse effects act contemporary at a biochemical and immunological level showing a great preventive action and efficacy and therapy. This is the road map for prevention and therapy based on the physiology revolution of “allostasis” (Sterling and Heyer) [8] substituting the obsolete concept of “Homeostasis”(Cannon) taught yet and unknown to most clinicians and investigators.

The anti-viral targets of prevention and a successful therapy anti-SARS-COV 2 variants of concern (VOC) must be addressed at the same time to prevent the virus binding to receptors, (barrier effect) inhibition of proteases, prevention of NK and CD8inactivation by viruses, re-activation of the P53 gene, preventing the critical anergy after the seventh day of the disease shared by patients with atherosclerosis -based comorbidities, reinforcement of natural humoral immunity, and prevention of the virus-induced viral allostatic metabolism and generation of anti-viral allostasis, prevention of cytokine storm-induced lung inflammation and antiviral allostasis in oral, nasal mucosae and upper respiratory ways, and an antiviral allostasis metabolism generation.

One of us recently introduced to the COVID prevention and early treatment of the epistemological concept of anti-viral allostasis and immunostimulation identifying the relativity of the SARS-COV 2 entry into cells and reviewing the anti-viral targets of naturals molecules spread worldwide [9] [10]  according to the Person-centered prevention strategy” inspired by Person-Centered Medicine, the current paradigm of Medical Science, [11] [12]  which at the clinical level introduced the Person-Centered Clinical Method that allows the physician the identification of the subjective-biological-environmental patient’s resources addressed to improve the person and lifestyle, [13]   not reducing the clinical case to be a probabilistic event of a natural law variation, [14] but concerning the relation with the person’s subjective being, comprising in existence and resulting in life quality related to the spiritual- psycho-neuro-endocrine, immunity  [15], and epigenetic individual system.

The COVID-19 prevention and early treatment inducing an anti-viral allostasis (AVAL) and immunostimulation (IMUST) is entrusted to the person’s natural immune system and can be reinforced by a resource-centered healthy lifestyle and powerful anti-viral substances with act as natural epigenetic programmers at immunity -biochemical level. Nutrition quality is part of a healthy or bad life quality. Curcumin, Aloe, Lactoferrin, Epigallocatechin, Beta-glucans Sphingosine, Mannan binding lectins, and Quercetin are natural molecules with a well-documented powerful pleiotropic antiviral allostasis and immunostimulant actions  [16] [17] . Vit A and C are immunostimulants and VIT D metabolite, [18] cathelicidin has direct virucide properties. Nimesulide has stronger anti-inflammatory and antiviral properties, with well-studied significant therapeutic successes,[19] and its association with maltodextrins results also in immunostimulation. [20] [21]  Doxiciclin has also antibacterial and antiviral properties. [22] Conversely the antipyretic tachipirine, suggested by the Italian Health Ministry to treat early COVID is dangerous because it promotes coagulation and has not ant-inflammatory effects. [23]

A sixty years old unvaccinated woman, a great smoker, with a determinate temperament and good basic trust, and a previous history of breast cancer with a swab positive diagnosis of COVID-19 developed a temperature of 40 degrees, with headache and cough, an indicator of a high cytokine storm. Tachipirin administration, prescribed by phone by an emergency unit according to the Italian health ministry indications was suspended and a translational therapy integrated with drugs was prescribed with the resolution of COVID-19 syndrome in four days and negativity of swab in 10 days. The woman started to work on the 11th day. Posology is indicated in table 1 (Table 1)

Genotoxic and immunosuppressive mRNA and vectorial vaccines, silencing microRNA and/or hybridizing DNA [24]  produce only circulating IGG, waning in a short time and are inactive against VOC not induce protective mucosal IGA and do not generate Memory B Cell in lungs [25]  with a high rate of life-threatening adverse effects. Cells’ methylation induces an increased risk of cancer. [26]     Monoclonal antibodies and anti-viral drugs have many adverse effects and are expensive, while translational medicine and its integration significant could promote effective prevention and therapy worldwide at low cost with high availability of natural anti-viral molecules. Moreover, there is the impossibility to vaccinate the entire world, and integrated therapy could offer cheap possibilities to all for self-care through health education. Person-centered translational prevention and therapy based on preventive antiviral allostasis and immuno-stimulation and self-care in poor countries all over the world, by correcting the epistemological error determining the failure of the pandemic prevention  is a new perspective for public health to prevent communicable and non-communicable diseases worldwide, without submitting people to experimental mass vaccines.

 

[1]    Lockhart J, Canfield J, Mong EF, Vanwye J, Totary-Jain H. Nucleotide Modification Alters MicroRNA-Dependent Silencing of MicroRNA Switches. Mol Ther Nucleic Acids. 2019;14:339-350. doi:10.1016/j.omtn.2018.12.00

[2]   Doerfler W. Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human Genome – Are Adenoviral Genes Expressed in Vector-based Vaccines? Virus Res. 2021 Sep;302:198466. doi: 10.1016/j.virusres.2021.198466. Epub 2021 Jun 1. PMID: 34087261; PMCID: PMC8168329.

[3]    Seneff, S., Nigh, G., Kyriakopoulos, A. M., & McCullough, P. A. Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs. Food and chemical toxicology 2022; 164, 113008. Internet:https://doi.org/10.1016/j.fct.2022.113008

[4]    Brera G.R. Scientific evidence of mRNA and vectorial vaccines genotoxicity inducing tumors and psycho-neuro-behavioral disorders. Scientific Report of the Milan School of Medicine; December 7 2021 DOI: 10.13140/RG.2.2.29151.18081

[5]    Cotton C. Lecture méthodologique desrésultats des essais cliniques des vaccins COVID-19. Internet   https://www.francesoir.fr/sites/francesoir/files/media-icons/Revue-des-Essais-Cliniques-COVID-Christine-Cotton.pdf

[6]    Cotton C. Evaluation des pratiques méthodologiques mises en œuvre dans les essais Pfizer dans le développement de son vaccin ARN-messager contre la COVID-19 en regard des Bonnes Pratiques Cliniques Présentation OPECTS Christine COTTON 1 A Maxime Beltra Christine COTTON – 05/04/2022 – © L

[7]     Brera, G.R. Person-Centered Medicine and Person Centered Clinical Method. Milano: Università Ambrosiana ed.: 2021 ISBN: 9798726465432

[8]    Sterling P.,Eyer J. Allostasis: a new paradigm to explain arousal pathology. In: Fischer S Reason J. editors. Handbook of Life Sciences, cognition, and Hea[7] Robinson E.G., Fernald R., Clayton D. Genes and Social Behavior.Science 2008;322:896-lth. New York 1988: J.Wiley and sons;p. 629-649

[9]    Brera G.R. SARS-COV 2 allostasis and the people and person-centered prevention. A new prevention strategy based on people’s metabolic and immune shield for the pandemic shutdown. Part 1 The Sars-Cov 2 entry and COVID-19. Milan. Università Ambrosiana , 2021. ISBN: 9798530093906

[10]    Brera G.R . SARS-COV 2- allostasis and the people   and person-centered prevention.  Part 2 The Sars-Cov 2- induced immunosuppression and covid-19 anergy. Part 3 The antiviral metabolic allostasis and preventive immunostimulation -How to induce zero risk for covid-19. Milan:  Ambrosiana University: 2021. ISBN: 9798547583520

[11]   7

[12]   Brera G. R, The manifesto of Person-Centred Medicine. Medicine, Mind and Adolescence 1999.XIV, 1-2:7-11

[13]  Brera, G.R. Person-Centered Medicine and Person Centered Clinical Method. Milano: Università Ambrosiana ed.: 2021 ISBN: 9798726465432

[14] Gadamer H-G Where health is hidden. Frankfurt; Suhrkamp Verlag, 1993 (German)

[15]  Lissoni P The spirit marries the science. Calco, Ripamonti tip, 2008 (Italian)

[16] 8-9

[17]  Qingqing Dai, Yasumasa Morita, Yongbo Huang, et al) Modulation of Human Neutrophil Peptides on P. aeruginosa Killing, Epithelial Cell Inflammation and Mesenchymal Stromal Cell Secretome Profiles. Journal of Inflammation Research. 2019; 12: 335-343

[18]  Mitra S, Paul S, Roy S, Sutradhar H, Bin Emran T, Nainu F, Khandaker MU, Almalki M, Wilairatana P, Mubarak MS. Exploring the Immune-Boosting Functions of Vitamins and Minerals as Nutritional Food Bioactive Compounds: A Comprehensive Review. Molecules. 2022 Jan 16;27(2):555. DOI: 10.3390/molecules27020555. PMID: 35056870; PMCID: PMC8779769.

[19]  Suter F, Consolaro E, Pedroni S, et al. A simple, home-therapy algorithm to prevent hospitalization for COVID-19 patients: A retrospective observational matched-cohort study. clinical medicine. 2021 Jul;37:100941. DOI: 10.1016/j.eclinm.2021.100941. Epub 2021 Jun 9. PMID: 34127959; PMCID: PMC8189543. (Medrix 25/03/2021

[20]  Gozzi-Silva SC, Teixeira FME, Duarte AJDS, Sato MN, Oliveira LM. Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve? Front Nutr. 2021 Sep 7;8:674258. doi: 10.3389/fnut.2021.674258. PMID: 34557509; PMCID: PMC8453008.

[21]   Martin TR, Frevert CW. Innate immunity in the lungs. Proc Am Thorac Soc. 2005;2(5):403-11.  DOI: 10.1513/pats.200508-090JS. PMID: 16322590; PMCID: PMC2713330.

[22]  Dorobisz K, Dorobisz T, Janczak D, Zatoński T. Doxycycline in the Coronavirus Disease 2019 Therapy. Ther Clin Risk Manag. 2021 Sep 21;17:1023-1026. doi: 10.2147/TCRM.S314923. PMID: 34584416; PMCID: PMC8464303.

[23]  Pandolfi S, Simonetti V, Ricevuti G, Chirumbolo S. Paracetamol in the home treatment of early COVID-19 symptoms: A possible foe rather than a friend for elderly patients? J Med Virol. 2021 Oct;93(10):5704-5706. doi: 10.1002/jmv.27158. Epub 2021 Jun 30. Erratum in: J Med Virol. 2022 Mar;94(3):1246. PMID: 34170556; PMCID: PMC8426871.

[24]   1-2-3-4

[25]  Federico M. Biological and Immune Responses to Current Anti-SARS-CoV-2 mRNA Vaccines beyond Anti-Spike Antibody Production. Journal of Immunology Research. 2022. DOI  https://doi.org/10.1155/2022/4028577

[26]  Huang L, Liang D, Zhang Y, et al. METTL3 promotes colorectal cancer metastasis by promoting the maturation of pri-microRNA-196b. J Cancer Res Clin Oncol. 2022 Nov 8. doi: 10.1007/s00432-022-04429-9. Epub ahead of print. PMID: 36348020.

 

 

 

 

 

 

 

 

 

Table 1

 

 Substance-molecule   Posology
   Curcumin Curcumin 500 mg x2

5’Inhalation of turmeric powder (10 g- two tea spoons) vapors  from a solution with 100 ml of water at boiled temperature

Aloe extract  50 ml x 2
Lactoferrin 200 mg x 2 before meals
Epigallocathechin  Infusion of green tea (40°) four glasses per  day ( 800 ml )
Resveratrol 1000 mg x 2 before meals
Sphingosine and Beta-glucans Kefir milk 200 ml x 3
Melatonin 5 mg ( evening
Vit D10 10.000 U ( 7 days) after  1000
Vit, C 500 mg
Vit A 1000 U
Nimesulide and maltodextrins 400 mg x 2
Doxiciclin 200 mg a day
Table 1  Posology of the integrated therapy-

( Doses are referred one-two times a day ,morning and evening)

 

 

Radiation Emitted by Wireless Devices and Male Reproductive Hormones

 2021; 12: 732420.
Published online 2021 Sep 24. doi: 10.3389/fphys.2021.732420
PMCID: PMC8497974
PMID: 34630149

Effect of Radiation Emitted by Wireless Devices on Male Reproductive Hormones: A Systematic Review

Exposure to radiofrequency electromagnetic radiation (RF-EMR) from various wireless devices has increased dramatically with the advancement of technology. One of the most vulnerable organs to the RF-EMR is the testes. This is due to the fact that testicular tissues are more susceptible to oxidative stress due to a high rate of cell division and mitochondrial oxygen consumption. As a result of extensive cell proliferation, replication errors occur, resulting in DNA fragmentation in the sperm. While high oxygen consumption increases the level of oxidative phosphorylation by-products (free radicals) in the mitochondria. Furthermore, due to its inability to effectively dissipate excess heat, testes are also susceptible to thermal effects from RF-EMR exposure. As a result, people are concerned about its impact on male reproductive function. The aim of this article was to conduct a review of literature on the effects of RF-EMR emitted by wireless devices on male reproductive hormones in experimental animals and humans. According to the findings of the studies, RF-EMR emitted by mobile phones and Wi-Fi devices can cause testosterone reduction. However, the effect on gonadotrophic hormones (follicle-stimulating hormone and luteinizing hormone) is inconclusive. These findings were influenced by several factors, which can influence energy absorption and the biological effect of RF-EMR. The effect of RF-EMR in the majority of animal and human studies appeared to be related to the duration of mobile phone use. Thus, limiting the use of wireless devices is recommended.

Keywords: mobile phone, Wi-Fi, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH)

ARTICLE

Long-term exposure to electromagnetic radiation decreases estrogens and prolactin

Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring

Affiliations 

Abstract

We investigated the effects of mobile phone (900 and 1800 MHz)- and Wi-Fi (2450 MHz)-induced electromagnetic radiation (EMR) exposure on uterine oxidative stress and plasma hormone levels in pregnant rats and their offspring. Thirty-two rats and their forty newborn offspring were divided into the following four groups according to the type of EMR exposure they were subjected to: the control, 900, 1800, and 2450 MHz groups. Each experimental group was exposed to EMR for 60 min/day during the pregnancy and growth periods. The pregnant rats were allowed to stand for four generations (total 52 weeks) before, plasma and uterine samples were obtained. During the 4th, 5th, and 6th weeks of the experiment, plasma and uterine samples were also obtained from the developing rats. Although uterine lipid peroxidation increased in the EMR groups, uterine glutathione peroxidase activity (4th and 5th weeks) and plasma prolactin levels (6th week) in developing rats decreased in these groups. In the maternal rats, the plasma prolactin, estrogen, and progesterone levels decreased in the EMR groups, while the plasma total oxidant status, and body temperatures increased. There were no changes in the levels of reduced glutathione, total antioxidants, or vitamins A, C, and E in the uterine and plasma samples of maternal rats. In conclusion, although EMR exposure decreased the prolactin, estrogen, and progesterone levels in the plasma of maternal rats and their offspring, EMR-induced oxidative stress in the uteri of maternal rats increased during the development of offspring. Mobile phone- and Wi-Fi-induced EMR may be one cause of increased oxidative uterine injury in growing rats and decreased hormone levels in maternal rats.

Graphical abstract: TRPV1 cation channels are the possible molecular pathways responsible for changes in the hormone, oxidative stress, and body temperature levels in the uterus of maternal rats following a year-long exposure to electromagnetic radiation exposure from mobile phones and Wi-Fi devices. It is likely that TRPV1-mediated Ca(2+) entry in the uterus of pregnant rats involves accumulation of oxidative stress and opening of mitochondrial membrane pores that consequently leads to mitochondrial dysfunction, substantial swelling of the mitochondria with rupture of the outer membrane and release of oxidants such as superoxide (O2 (-)) and hydrogen peroxide (H2O2). The superoxide radical is converted to H2O2 by superoxide dismutase (SOD) enzyme. Glutathione peroxidase (GSH-Px) is an important antioxidant enzyme for removing lipid hydroperoxides and hydrogen peroxide and it catalyzes the reduction of H2O2 to water.

Translate »