Corona Virus How To Treat

[md_a]

**** **** **** **** ****! Medium censored a good piece again. **** **** ****!

Regarding the article
Ray Peat:
The article sounds to me like the ideas of students who have taken a pharmacology course in computer modeling of molecules; without an anchor to experiment, it’s perfectly useless. Iron and particulate pollution cause lung damage similar to the inflammation produced by the virus. Ventilating patients decreases their antiinflammatory CO2, making the inflammation worse. Acetaminophen, often given to patients, increases lung nitric oxide and damages red blood cells, adding to the harm done by treatment. The suggested treatments could aggravate the damage; for example, chloroquine increases nitric oxide. The angiotensin produced in response to the virus increases nitric oxide, and blocking that protects from the virus.
J Clin Invest. 1998 Aug 1; 102(3): 595–605.
Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.
D Ghigo, E Aldieri, R Todde, C Costamagna, G Garbarino, G Pescarmona, and A Bosia
Abstract
Nitric oxide (NO) is a free radical involved in the regulation of many cell functions and in the expression of several diseases. We have found that the antimalarial and antiinflammatory drug, chloroquine, is able to stimulate NO synthase (NOS) activity in murine, porcine, and human endothelial cells in vitro: the increase of enzyme activity is dependent on a de novo synthesis of some regulatory protein, as it is inhibited by cycloheximide but is not accompanied by an increased expression of inducible or constitutive NOS isoforms. Increased NO synthesis is, at least partly, responsible for chloroquine-induced inhibition of cell proliferation: indeed, NOS inhibitors revert the drug-evoked blockage of mitogenesis and ornithine decarboxylase activity in murine and porcine endothelial cells. The NOS-activating effect of chloroquine is dependent on its weak base properties, as it is exerted also by ammonium chloride, another lysosomotropic agent. Both compounds activate NOS by limiting the availability of iron: their stimulating effects on NO synthesis and inhibiting action on cell proliferation are reverted by iron supplementation with ferric nitrilotriacetate, and are mimicked by incubation with desferrioxamine. Our results suggest that NO synthesis can be stimulated in endothelial cells by chloroquine via an impairment of iron metabolism.

 

[yerrag]

Regarding the article
Ray Peat:
The article sounds to me like the ideas of students who have taken a pharmacology course in computer modeling of molecules; without an anchor to experiment, it’s perfectly useless. Iron and particulate pollution cause lung damage similar to the inflammation produced by the virus. Ventilating patients decreases their antiinflammatory CO2, making the inflammation worse. Acetaminophen, often given to patients, increases lung nitric oxide and damages red blood cells, adding to the harm done by treatment.

The article does not talk about acetaminophen. Did you mix things up?

 

[md_a]

The article does not talk about acetaminophen. Did you mix things up?

I sent him that article and asked him what he thinks, I didn't mention anything about acetaminophen.

 

[yerrag]

I sent him that article and asked him what he thinks, I didn't mention anything about acetaminophen.

Sorry, I guess he brought up acetaminophen as an example to build up to the subject matter.

I have to read it again and again.

 

[yerrag]

I sent him that article and asked him what he thinks, I didn't mention anything about acetaminophen.

The mention of acetaminophen by Ray is his way of giving an example of something that increases nitric oxide. Without having to mention acetaminophen, he can still go direct to the point and simply say that hydrochloroquine increases nitric oxide, which according to him is harmful to red blood cells. But saying nitric oxide is harmful is a simplification. If the nitric oxide were turned into ROS, it would be harmful to red blood cells. But then, there's an enzyme called G6PD which protects the red blood cells from getting oxidized and damaged by ROS. And then we have to consider that ROS is also used to destroy pathogens, so it's not all bad, especially when antioxidants are present to minimize damage by ROS on tissues. So, while hydrochloroquine isn't perfect, it isn't so bad either.

 

[Wagner83]

Very cheery note, thank you! LOL.

Watch out, you are showing symptoms of gbolitis.

I’m grateful for doctors. The only 4 medical advances are aspirin, antibiotics, insulin and ER medicine if you get into an accident. Thankfully my illness fell within the domain of medical competence at least at the end. My object was always to stay out of the hospital. I got better rapidly and then pneumonia set in quickly. I was listening to a medical lecturer on pneumonia and he said young and healthy people show very strong symptoms especially respiratory, and older people just feel kind of “blah” when they had pneumonia. I had strong symptoms and felt “blah”, lol, luckily so I knew pneumonia was a strong possibility. It sets in quickly, very quickly.

I doubt I’ll get worse. It’s possible but I feel no sign of it.

There was an interesting story today how people who supposedly had COVID-19 have no antibodies and could “be reinfected.” But I don’t think this is so. I think they have cellular immunity, lysogeny, and they don’t need to bother their Thymus-based immune system with it. If they tested their cells, their cells wouldn’t be susceptible to the virus, having the provirus. In modern virology, there is no difference between the provirus and the virus. It’s a complete mess, a false model, resulting in errors everywhere. Similar to pure oxygen from the basic misunderstanding of CO2, this Fundamental Error of Virology results in fake vaccines that stimulate the immune system to generate massive response that can hurt us, without conferring immunity at all from the provirus.

I didn't say you would get worse and hope you don't. I don't blame you for being sick either. By the way, people who are hospitalized for corona have bad respiratory issues, as you know. If you read this forum , 99% of those hospitalized people are above 70 with comorbidities.
Anyways, here was my issue :

• You don't know which virus you had.
• You treated yourself with self-administered medicine, and improved at first.
• Then you got worse. If I understood correctly, the 'getting worse' part was also life-threatening. So despite combining all the different drugs you/Ray thought would cure it, you had to take a strong, unrelated antibiotic to heal.
• Yet, replying to a member's question on this thread, you state the first treatment you took worked for coronavirus.

So, when making statements to other members and readers who might get infected, or have relatives who might get infected, more care would be welcome.

 

[md_a]

The mention of acetaminophen by Ray is his way of giving an example of something that increases nitric oxide. Without having to mention acetaminophen, he can still go direct to the point and simply say that hydrochloroquine increases nitric oxide, which according to him is harmful to red blood cells. But saying nitric oxide is harmful is a simplification. If the nitric oxide were turned into ROS, it would be harmful to red blood cells. But then, there's an enzyme called G6PD which protects the red blood cells from getting oxidized and damaged by ROS. And then we have to consider that ROS is also used to destroy pathogens, so it's not all bad, especially when antioxidants are present to minimize damage by ROS on tissues. So, while hydrochloroquine isn't perfect, it isn't so bad either.

I don't think pathogens kill people, but the body's response by mediators of inflammation in excess on a weak metabolism. Focusing on destroying pathogens without taking into account the immune system I think is risky.


Glucose‐6‐phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase‐derived reactive oxygen species

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Summary

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose‐6‐phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2‐mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6‐aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti‐oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS‐induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2‐derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.


In summary we have demonstrated for the first time, to the best of our knowledge, that increase in NOX2‐derived ROS generation is dependent upon enhanced G6PD and decreased GR activity in the AECs of LPS‐treated mice. More importantly, suppression of G6PD activity by 6‐aminonicotinamide leads to a decrease in airway inflammation/permeability due probably to reduction in NOX2‐derived ROS and subsequent oxidative stress. Our results imply that G6PD might be a novel target for therapeutic intervention to reduce NOX2‐derived oxidative stress, and ameliorate pulmonary inflammation during ALI.


Reactive Oxygen Species In Acute Respiratory Distress Syndrome (ARDS)

In the metabolism of almost all human cells, a sequential addition of electrons to oxygen leads to the formation of reactive oxygen species (ROS). ROS have been implicated in more than 100 diseases and may be the common denominator in the pathogenesis of the most important health problems facing the world today. The last decade has been characterized by a progressive increase in the understanding of oxidant chemistry and the role of ROS in pulmonary disease. The majority of deaths among critically ill patients are the result of sepsis and its sequelae, including acute respiratory distress syndrome (ARDS). Nurses must understand the processes involving ROS that are in play when they are caring for patients with ARDS.

….

In addition to neutrophil activation, the unavoidable requirement of ARDS patients for high inspired oxygen concentrations (Fio2) also contributes to oxidative stress. Oxidant stress may be defined as an imbalance between the generation of oxygen derived species and the level of antioxidant protection within a system. Normally these are approximately in balance, but when the balance is tipped in favor of oxygen derived species cellular biochemistry is disturbed and a state of `oxidative stress` exists, which can lead to molecular damage. ARDS is an acute lung syndrome in which patients are experiencing severe oxidative stress from the disease process as well as from treatment with high Fio2 regimens.

…

Hyperoxia (a state in which oxygen supply is excessive) also appears to amplify the susceptibility of lung cells to neutrophil mediated oxidant damage.

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When tissue is injured, phagocytic cells migrate to the area as an inflammatory response develops, squeezing through the endothelial cells of the blood vessels into the inflamed tissue. They then phagocytize the offending bacteria and become activated via chemical signals such as cytokines. A marked increase in oxygen uptake occurs, often called the respiratory burst. This respiratory burst produces large amounts of ROS, mainly O2.-, OH . and H2O2, in an effort to kill the bacteria. Clearly, if the balance of ROS is tipped to excess, the ROS can cause tissue damage themselves.

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Free radicals

Usually, electrons move around the nucleus of an atom in pairs. Free radicals are chemical species capable of independent existence with only a single (unpaired) electron in an outer orbit. The unpaired electron is represented as a bold superscripted dot. The hydrogen atom (H.) is the simplest free radical because it contains 1 proton and 1 electron. Oxygen, too, is a radical because its 2 unpaired electrons are in different orbitals. This unstable configuration usually makes free radicals more reactive than nonradicals. However, the chemical reactivity of radicals varies immensely. Their importance in biology is in modulating tissue injury and molecular signaling. Free radicals react with adjacent molecules such as proteins, lipids, and carbohydrates—especially with those in cell membranes and nucleic acids (as in DNA). Oxidative damage to proteins leads to functional impairment or may mark them for rapid destruction by other mechanisms. Cross-linking of cell membrane proteins caused by free radicals can result in the formation of ion channels or otherwise disrupt membrane structure and function. DNA is highly sensitive to free-radical damage. Nucleic acids are attacked resulting in strand breaks that can lead to mutations. The exact mechanisms involved in gene expression after oxidative damage are not well understood, but DNA damage has been implicated in aging and in the malignant transformation of cells. Free radicals can also catalyze reactions among themselves, producing a chain reaction of damage.

Lipid peroxidation is an important reaction of this type. Cell membranes are rich in polyunsaturated fatty acids (PUFAs), which are particularly susceptible to oxidative damage. In the presence of oxygen, free radicals initiate damage to membrane lipids by attacking the double bonds in PUFAs. The lipid-radical reactions yield peroxides, which are also unstable, and a chain reaction ensues that can result in extensive cellular damage.

Oxidative stress

In health, the formation of ROS is balanced by antioxidant defenses. There exists a wide variety of intracellular and extracellular antioxidants in human physiology, including enzymes, small molecules, and the sequestration of metal ions that either block the formation of ROS or inactivate them (as “scavengers”). Free-radical scavengers (such as glutathione peroxidase, urate, α-tocopherol and ascorbate) often remove free radicals by reacting with them directly (noncatalytically). Any disruption of this balance leads to the pathogenesis of many human diseases and aging. A shift in a cell’s status to a more oxidized state with resultant damage is termed oxidative stress. Oxidative stress can be considered pathologic, but it is also adaptive and physiologic in some situations. Thus, excessive oxidation may become “poisonous,” as with all toxicants.

List of antioxidants: Albumin, Antioxidants, Apotransferrin, Bilirubin, Caeruloplasmin, Catalase, Glucose, Glutathione peroxidase, Haptoglobin, Hemopexin, Lactoferrin, Red blood cell anion channels, Selenium, Superoxide dismutases, Transferrin, Uric acid, Vitamin C (ascorbate), Vitamin E (α-tocopherol)

Risk factors for ARDS: Oxygen toxicity, Aspiration, Cardiopulmonary bypass, Chronic alcoholism, Chronic liver disease, Hemorrhagic shock, Lung contusion, Major trauma, Multiple transfusions, Near drowning, Pancreatitis, Pneumonia, Sepsis, Severe burns

The production of ROS can be greatly increased by the therapeutic administration of oxygen (thus supplying extra oxygen for oxidation/production of ROS) and certain drugs (such as nitrofurantoin and bleomycin). Hyperoxic lung toxicity results when production of ROS exceeds the antioxidant capacity of the cells. The metabolism of oxygen by lung cells increases as arterial pressure of oxygen increases. Therapeutic use of high O2 concentrations in ARDS patients may be implicated in exacerbating the primary injury. Drug-induced oxidant lung injury is thought to be caused by the generation of superoxide, leading to the generation of OH during metabolism of the drug, and is, therefore, a chemical form of oxygen toxicity.

Patients diagnosed with ARDS tend to have decreased plasma iron-binding antioxidant activity, and therefore a decreased ability to prevent iron dependent ROS formation. They may also have completely saturated plasma iron-binding proteins, which leaves free iron available for reactions producing ROS. The intentional depletion of iron, either by diet change or iron chelator administration, can reduce the risk of bleomycin toxicity.

…..

The prime cause of cancer is increasing the amounts of Reactive Oxygen Species (ROS) and inflammation inside healthy human eukaryotic cells which through the Butterfly Effect results in the damage and wrong messages from DNA to the mitochondria and causes the shutdown of them. Fear causes the increase in the amounts of adrenaline and cortisol hormones from adrenal glands. Cortisol hormone suppresses the immune system, causes inflammation and increases the blood glucose level. Adrenaline causes hypocapnia, decreases the blood flow to the brain and suppresses the function of the digestive system. Hypocapnia and high blood glucose in blood results in the hypoxia in tissues through the Bohr Effect based on Otto Warburg Hypothesis, chronic hypoxia is related to the cause of cancer in healthy cells. Low blood flow to the brain causes hypoxia in the brain tissues as well. In conclusion, chronic fear results cancer incidence in humans through increasing the amounts of ROS, inflammation and hypoxia in tissues especially in the brain and digestive systems.


Reactive oxygen species in acute respiratory distress syndrome. - PubMed - NCBI

ARDS Acute Respiratory Distress in Adults

How Chronic Fear Results In Hypoxia in Tissues and Cancer in Humans through Bohr Effect

 

[yerrag]

Focusing on destroying pathogens without taking into account the immune system I think is risky.

It's knowing that nitric oxide can be friend and knowing when and when not to use it that makes a difference. Just because HCQ (hydrochloroquine) can increase nitric oxide does not necessarily mean it has to produce negative effects or outcomes. How phagocytosis of pathogens works as part of the immune system is also dependent on having ROS and free radicals, derived partly from nitric oxide, available as part of the tool chest of the immune system. Whoever talked about disregarding the role of the immune system?

Still, Ray's point about the oxidative stress of nitric oxide on red blood cells is something that has to be considered. This may be a matter of dosage, or a matter also of ensuring there is sufficient anti-oxidants to balance the oxidative stresses.

 

[md_a]

It's knowing that nitric oxide can be friend and knowing when and when not to use it that makes a difference. Just because HCQ (hydrochloroquine) can increase nitric oxide does not necessarily mean it has to produce negative effects or outcomes. How phagocytosis of pathogens works as part of the immune system is also dependent on having ROS and free radicals, derived partly from nitric oxide, available as part of the tool chest of the immune system. Whoever talked about disregarding the role of the immune system?

Still, Ray's point about the oxidative stress of nitric oxide on red blood cells is something that has to be considered. This may be a matter of dosage, or a matter also of ensuring there is sufficient anti-oxidants to balance the oxidative stresses.

Not only hydroxychloroquine increases nitric oxide but it is also stimulated as a mediator of inflammation from pathogen and is used in an emergency for oxygenation and other things. At the same time, nitric oxide produced in excess along with other inflammatory mediators causes fluid and protein leakage and eventually leads to hypoxia. I think it is more appropriate to use carbon dioxide for healing and things that stimulate immunity to solve the pathogenic problem more effectively and without high risks.



Capillary permeability

Additional chemotactic factors released include endotoxins (such those present in septic states), tumor necrosis factor and interleukin-1. The activated neutrophils release several inflammatory mediators and platelet aggravating factors that damage the alveolar capillary membrane and increase capillary permeability.

Histamine and other inflammatory substances increase capillary permeability allowing fluids to move into the interstitial space. Consequently, the patient experience tachypnea, dyspnea, and tachycardia. As capillary permeability increases, proteins, blood cells, and more fluid leak out, increasing interstitial pressure and causing pulmonary edema. Tachycardia, dyspnea, and cyanosis may occur. Hypoxia (usually unresponsive to increasing fraction of inspired oxygen), decreased pulmonary compliance, crackles, and rhonchi develop. The resulting pulmonary edema and hemorrhage significantly reduce lung compliance and impair alveolar ventilation. The fluid in the alveoli and decreased blood flow damage surfactant in the alveoli. The reduces the ability of alveolar cells to produce more surfactant. Without surfactant, alveoli and bronchioles fill with fluid or collapse, gas exchange is impaired, and the lungs are much less compliant. Ventilation of the alveoli is further decreased. The burden of ventilation and gas exchange shifts to uninvolved areas of the lung, and pulmonary blood flow is shunted from right to left. The work of breathing is increased, and the patient may develop thick, frothy sputum and marked hypoxemia with increasing respiratory distress.

Mediators released by neutrophils and macrophages also cause varying degrees of pulmonary vasoconstriction, resulting in pulmonary hypertension. The result of the changes is a ventilation-perfusion mismatch. Although the patient responds with an increased respiratory rate, sufficient oxygen can’t cross the alveolar capillary membrane. Carbon dioxide continues to cross easily and is lost with every exhalation. As oxygen and carbon dioxide levels in the blood decrease, the patient develops increasing tachypnea, hypoxemia, and hypocapnia (low partial pressure of arterial carbon dioxide [PaCO2]).

Pulmonary edema worsens, and hyaline membranes form. Inflammation leads to fibrosis, which further impedes gas exchange. Fibrosis progressively obliterates alveoli, respiratory bronchioles, and the interstitium. Functional residual capacity decreases, and shunting becomes more serious. Hypoxemia leads to metabolic acidosis. At this stage, the patient develops increasing PaCO2, decreasing Ph and partial pressure of arterial oxygen (PaO2), decreasing bicarbonate (HCO3-) levels, and mental confusion.

The end result is respiratory failure. Systematically, neutrophils and inflammatory mediators cause generalized endothelial damage and increased capillary permeability throughout the body. Multiple organ dysfunction syndrome (MODS) occurs as the cascade of mediators affects each system. Death may occur from the influence of ARDS and MODS.



Local inflammatory responses

Summary:

Inflammation is the response of the body's vascularized tissues to harmful stimuli such as infectious agents, mechanical damage, chemical irritants, etc. Inflammation has both local and systemic manifestations and may be either acute or chronic. Local inflammatory response (local inflammation) occurs within the area affected by the harmful stimulus. Acute local inflammation develops within minutes or hours after the influence of a harmful stimulus, has a short duration, and primarily involves the innate immune system. The five classic signs of acute local inflammation are redness, swelling, heat, pain, and loss of function. These classical signs result from the sequence of events that are triggered by tissue damage and allow leukocytes to get to the site of damage to eliminate the causative factor. This sequence involves changes in local hemodynamics and vessel permeability, as well as a complex interaction of leukocytes with endothelium and interstitial tissue through which leukocytes escape the blood vessels. To sustain the vascular changes and attract more immune cells to the site of inflammation, leukocytes and tissue cells secrete a range of inflammatory mediators including interleukins and chemokines. Elimination of the causative factor by leukocytes leads to the resolution of acute inflammation and tissue repair with complete regeneration or scarring. Failure to eliminate the causative agent or prolonged exposure to the causative agent leads to chronic inflammation. It aims to confine the causative agent, may last months to years and primarily involves the adaptive immune system.

Acute local inflammation:

Acute inflammation is an immediate response to a pathogenic factor (e.g., trauma or infection) and has the following features:

Rapid onset (occurs minutes to hours after an encounter with a causative factor)

Transient and typically short-lasting (provided it is not caused by an immunological condition)

Involves the innate immune system

Characterized by five classic signs of inflammation, which are caused by the release of inflammatory mediators

The sequence of events in inflammatory response include:

Local hemodynamic changes (vasoconstriction → vasodilation)

Increase in vascular permeability

Extravasation of leukocytes

Phagocytosis and killing of the phagocytosed pathogen or lysis of the phagocytosed particles

Outcome of inflammatory response:

Mechanism / Signs:

Redness / Heat:

Release of vasoactive mediators by immune cells and endothelium → vasodilation → ↑ blood flow;

Mediators: Histamine, Bradykinin, Prostaglandins (PGE2, PGD2, and PGF2), NO

Swelling:

Release of mediators from immune cells and endothelium or damage to endothelium → separation of endothelial junctions → separation of endothelial cells → ↑ vascular permeability and ↑ paracellular movement of fluid → leakage of protein-rich fluid to the interstitial tissue → ↑ oncotic tissue in the interstitium → accumulation of fluid in the interstitium;

Mediators: Histamine, Leukotrienes (C4, D4, T4), Serotonin

Pain:

Stimulation of free nerve endings by certain mediators and H+ ;

Prolonged stimulation → sensitization of ion channels (e.g., TRPV1) → hyperalgesia;

Mediators: Bradykinin, PGE2

Loss of function:

Caused by the combined effect of other cardinal signs

Local hemodynamic changes:

Initial transient reflectory vasoconstriction followed by vasodilation

Vasodilation is induced by release of inflammatory mediators:

Mediator: Histamine Source: Basophils, platelets, mast cells

Mediator: Serotonin Source: Platelets

Mediator: Prostaglandins (PGE2, PGD2, and PGF2) Source:Leukocytes, platelets, endothelial cells

Mediator: Bradykinin Source: Plasma

Mediator: NO Source: Endothelial cells

Due to increased diameter of vessels and leakage of protein-rich fluid into the interstitial tissue, blood stasis occurs, which allows for margination of leukocytes.

Increase in vascular permeability:

Mechanisms

Retraction of endothelial cells

Due to the action of inflammatory mediators (histamine, serotonin, bradykinin, leukotrienes C4, D4, and T4); Occurs rapidly and does not last long; Results in opening of interendothelial spaces and paracellular leakage of plasma; Endothelial injury; Results in endothelial cell necrosis and detachment; Leakage lasts until the damaged area is thrombosed or repaired.

Effects

Leads to leakage of plasma content into the interstitial tissue, causing local edema; Allows migration of immune cells and proteins to site of injury or infection

Chemotaxis and leukocyte extravasation:

Within inflamed tissue, leukocytes (mainly neutrophils in early infection) interact with the vascular endothelium and leave the blood vessels to migrate to the site of infection. The process of neutrophil extravasation from the blood to the inflamed tissue occurs in 5 steps: margination, rolling, adhesion, diapedesis, and migration

Chronic local inflammation:

Chronic local inflammation is due to nondegradable pathogens, prolonged exposure to toxic pathogens, or autoimmune reactions.

Cells involved: mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts

Leads to necrosis and fibrosis (simultaneous destruction and formation of new tissue)

May last for months to years

Mechanism involves two ways of activating macrophages

Classical (proinflammatory): mediated by Th1 cells secreting IFN-γ

Alternative (anti-inflammatory): mediated by Th2 cells secreting IL-4 and IL-13

Outcomes

Scarring

Amyloidosis

Neoplasia (e.g., chronic HCV infection → chronic hepatitis → hepatocellular carcinoma)

Granulomatous inflammation:

Granulomatous inflammation is a distinct type of chronic inflammation that is characterized by the formation of granulomas in the affected tissue. If the immune system is unable to completely eliminate a foreign substance (e.g., persistent pathogen, foreign body), the resulting granulomatous inflammation attempts to wall off the foreign substance within granulomas without completely degrading or eradicating it.

Pathophysiology:

Antigen-presenting cells present antigens to CD4+ Th cells and secrete IL-12 → stimulate differentiation into Th1 cells → Th1 cells activate macrophages by secreting IFN-γ → macrophages release cytokines (e.g., TNF), which stimulates the formation of epithelioid macrophages and giant cells

Epithelioid cells secrete TNF-α, which serves to maintain the granuloma.

Macrophages within the granuloma ↑ calcitriol (1,25-[OH]2 vitamin D3) activation → hypercalcemia


Local inflammatory responses – Knowledge for medical students and physicians

 

[schultz]

Regarding the article
Ray Peat:
The article sounds to me like the ideas of students who have taken a pharmacology course in computer modeling of molecules; without an anchor to experiment, it’s perfectly useless. Iron and particulate pollution cause lung damage similar to the inflammation produced by the virus. Ventilating patients decreases their antiinflammatory CO2, making the inflammation worse. Acetaminophen, often given to patients, increases lung nitric oxide and damages red blood cells, adding to the harm done by treatment. The suggested treatments could aggravate the damage; for example, chloroquine increases nitric oxide. The angiotensin produced in response to the virus increases nitric oxide, and blocking that protects from the virus.
J Clin Invest. 1998 Aug 1; 102(3): 595–605.
Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.
D Ghigo, E Aldieri, R Todde, C Costamagna, G Garbarino, G Pescarmona, and A Bosia
Abstract
Nitric oxide (NO) is a free radical involved in the regulation of many cell functions and in the expression of several diseases. We have found that the antimalarial and antiinflammatory drug, chloroquine, is able to stimulate NO synthase (NOS) activity in murine, porcine, and human endothelial cells in vitro: the increase of enzyme activity is dependent on a de novo synthesis of some regulatory protein, as it is inhibited by cycloheximide but is not accompanied by an increased expression of inducible or constitutive NOS isoforms. Increased NO synthesis is, at least partly, responsible for chloroquine-induced inhibition of cell proliferation: indeed, NOS inhibitors revert the drug-evoked blockage of mitogenesis and ornithine decarboxylase activity in murine and porcine endothelial cells. The NOS-activating effect of chloroquine is dependent on its weak base properties, as it is exerted also by ammonium chloride, another lysosomotropic agent. Both compounds activate NOS by limiting the availability of iron: their stimulating effects on NO synthesis and inhibiting action on cell proliferation are reverted by iron supplementation with ferric nitrilotriacetate, and are mimicked by incubation with desferrioxamine. Our results suggest that NO synthesis can be stimulated in endothelial cells by chloroquine via an impairment of iron metabolism.

Excellent stuff. Thanks for sharing this.

 

[yerrag]

I think it is more appropriate to use carbon dioxide for healing and things that stimulate immunity to solve the pathogenic problem more effectively and without high risks.

Give me instances where CO2 by itself will heal a patient suffering from COVID-19.

Perhaps as part of a protocol, the use of carbogen can be helpful. But hydrochloroquine and CO2 are not mutually interchangeable as treatment for COVID-19.

 

[ecstatichamster]

Watch out, you are showing symptoms of gbolitis.



I didn't say you would get worse and hope you don't. I don't blame you for being sick either. By the way, people who are hospitalized for corona have bad respiratory issues, as you know. If you read this forum , 99% of those hospitalized people are above 70 with comorbidities.
Anyways, here was my issue :

• You don't know which virus you had.
• You treated yourself with self-administered medicine, and improved at first.
• Then you got worse. If I understood correctly, the 'getting worse' part was also life-threatening. So despite combining all the different drugs you/Ray thought would cure it, you had to take a strong, unrelated antibiotic to heal.
• Yet, replying to a member's question on this thread, you state the first treatment you took worked for coronavirus.

So, when making statements to other members and readers who might get infected, or have relatives who might get infected, more care would be welcome.

I never said I had Coronavirus. Most likely I think h1n1 flu but who knows. I did get better then bacterial pneumonia set in. I did not just suddenly get worse. I had felt quite recovered before pneumonia which sets in really fast.

 

[theLaw]

Extended interview with Cameron Kyle-Sidell, MD, and ICU doc in Maimonides in Brooklyn, New York about concerns with using ventilators for treatment:

Do COVID-19 Vent Protocols Need a Second Look?

.............and it appears that hospitals are changing their protocols for using ventilators:

Some doctors moving away from ventilators for virus patients

 

[Collden]

Covid-19 had us all fooled, but now we might have finally found its s…


Covid-19 had us all fooled, but now we might have finally found its secret.

In the last 3–5 days, a mountain of anecdotal evidence has come out of NYC, Italy, Spain, etc. about COVID-19 and characteristics of patients who get seriously ill. It’s not only piling up but now leading to a general field-level consensus backed up by a few previously little-known studies that we’ve had it all wrong the whole time. Well, a few had some things eerily correct (cough Trump cough), especially with Hydroxychloroquine with Azithromicin, but we’ll get to that in a minute.
There is no ‘pneumonia’ nor ARDS. At least not the ARDS with established treatment protocols and procedures we’re familiar with. Ventilators are not only the wrong solution, but high pressure intubation can actually wind up causing more damage than without, not to mention complications from tracheal scarring and ulcers given the duration of intubation often required… They may still have a use in the immediate future for patients too far to bring back with this newfound knowledge, but moving forward a new treatment protocol needs to be established so we stop treating patients for the wrong disease.
The past 48 hours or so have seen a huge revelation: COVID-19 causes prolonged and progressive hypoxia (starving your body of oxygen) by binding to the heme groups in hemoglobin in your red blood cells. People are simply desaturating (losing o2 in their blood), and that’s what eventually leads to organ failures that kill them, not any form of ARDS or pneumonia. All the damage to the lungs you see in CT scans are from the release of oxidative iron from the hemes, this overwhelms the natural defenses against pulmonary oxidative stress and causes that nice, always-bilateral ground glass opacity in the lungs. Patients returning for re-hospitalization days or weeks after recovery suffering from apparent delayed post-hypoxic leukoencephalopathy strengthen the notion COVID-19 patients are suffering from hypoxia despite no signs of respiratory ‘tire out’ or fatigue.
Here’s the breakdown of the whole process, including some ELI5-level cliff notes. Much has been simplified just to keep it digestible and layman-friendly.
Your red blood cells carry oxygen from your lungs to all your organs and the rest of your body. Red blood cells can do this thanks to hemoglobin, which is a protein consisting of four “hemes”. Hemes have a special kind of iron ion, which is normally quite toxic in its free form, locked away in its center with a porphyrin acting as it’s ‘container’. In this way, the iron ion can be ‘caged’ and carried around safely by the hemoglobin, but used to bind to oxygen when it gets to your lungs.
When the red blood cell gets to the alveoli, or the little sacs in your lungs where all the gas exchange happens, that special little iron ion can flip between FE2+ and FE3+ states with electron exchange and bond to some oxygen, then it goes off on its little merry way to deliver o2 elsewhere.
Here’s where COVID-19 comes in. Its glycoproteins bond to the heme, and in doing so that special and toxic oxidative iron ion is “disassociated” (released). It’s basically let out of the cage and now freely roaming around on its own. This is bad for two reasons:
1) Without the iron ion, hemoglobin can no longer bind to oxygen. Once all the hemoglobin is impaired, the red blood cell is essentially turned into a Freightliner truck cab with no trailer and no ability to store its cargo.. it is useless and just running around with COVID-19 virus attached to its porphyrin. All these useless trucks running around not delivering oxygen is what starts to lead to desaturation, or watching the patient’s spo2 levels drop. It is INCORRECT to assume traditional ARDS and in doing so, you’re treating the WRONG DISEASE. Think of it a lot like carbon monoxide poisoning, in which CO is bound to the hemoglobin, making it unable to carry oxygen. In those cases, ventilators aren’t treating the root cause; the patient’s lungs aren’t ‘tiring out’, they’re pumping just fine. The red blood cells just can’t carry o2, end of story. Only in this case, unlike CO poisoning in which eventually the CO can break off, the affected hemoglobin is permanently stripped of its ability to carry o2 because it has lost its iron ion. The body compensates for this lack of o2 carrying capacity and deliveries by having your kidneys release hormones like erythropoietin, which tell your bone marrow factories to ramp up production on new red blood cells with freshly made and fully functioning hemoglobin. This is the reason you find elevated hemoglobin and decreased blood oxygen saturation as one of the 3 primary indicators of whether the ***t is about to hit the fan for a particular patient or not.
2) That little iron ion, along with millions of its friends released from other hemes, are now floating through your blood freely. As I mentioned before, this type of iron ion is highly reactive and causes oxidative damage. It turns out that this happens to a limited extent naturally in our bodies and we have cleanup & defense mechanisms to keep the balance. The lungs, in particular, have 3 primary defenses to maintain “iron homeostasis”, 2 of which are in the alveoli, those little sacs in your lungs we talked about earlier. The first of the two are little macrophages that roam around and scavenge up any free radicals like this oxidative iron. The second is a lining on the walls (called the epithelial surface) which has a thin layer of fluid packed with high levels of antioxidant molecules.. things like abscorbic acid (AKA Vitamin C) among others. Well, this is usually good enough for naturally occurring rogue iron ions but with COVID-19 running rampant your body is now basically like a progressive state letting out all the prisoners out of the prisons… it’s just too much iron and it begins to overwhelm your lungs’ countermeasures, and thus begins the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to all that nasty stuff and damage you see in CT scans of COVID-19 patient lungs. Ever noticed how it’s always bilateral? (both lungs at the same time) Pneumonia rarely ever does that, but COVID-19 does… EVERY. SINGLE. TIME.
— — — — — — — — — — — — -
Once your body is now running out of control, with all your oxygen trucks running around without any freight, and tons of this toxic form of iron floating around in your bloodstream, other defenses kick in. While your lungs are busy with all this oxidative stress they can’t handle, and your organs are being starved of o2 without their constant stream of deliveries from red blood cell’s hemoglobin, and your liver is attempting to do its best to remove the iron and store it in its ‘iron vault’. Only its getting overwhelmed too. It’s starved for oxygen and fighting a losing battle from all your hemoglobin letting its iron free, and starts crying out “help, I’m taking damage!” by releasing an enzyme called alanine aminotransferase (ALT). BOOM, there is your second of 3 primary indicators of whether the ***t is about to hit the fan for a particular patient or not.
Eventually, if the patient’s immune system doesn’t fight off the virus in time before their blood oxygen saturation drops too low, ventilator or no ventilator, organs start shutting down. No fuel, no work. The only way to even try to keep them going is max oxygen, even a hyperbaric chamber if one is available on 100% oxygen at multiple atmospheres of pressure, just to give what’s left of their functioning hemoglobin a chance to carry enough o2 to the organs and keep them alive. Yeah we don’t have nearly enough of those chambers, so some fresh red blood cells with normal hemoglobin in the form of a transfusion will have to do.
The core point being, treating patients with the iron ions stripped from their hemoglobin (rendering it abnormally nonfunctional) with ventilator intubation is futile, unless you’re just hoping the patient’s immune system will work its magic in time. The root of the illness needs to be addressed.
Best case scenario? Treatment regimen early, before symptoms progress too far. Hydroxychloroquine (more on that in a minute, I promise) with Azithromicin has shown fantastic, albeit critics keep mentioning ‘anecdotal’ to describe the mountain, promise and I’ll explain why it does so well next. But forget straight-up plasma with antibodies, that might work early but if the patient is too far gone they’ll need more. They’ll need all the blood: antibodies and red blood cells. No help in sending over a detachment of ammunition to a soldier already unconscious and bleeding out on the battlefield, you need to send that ammo along with some hemoglobin-stimulant-magic so that he can wake up and fire those shots at the enemy.
The story with Hydroxychloroquine
All that hilariously misguided and counterproductive criticism the media piled on chloroquine (purely for political reasons) as a viable treatment will now go down as the biggest Fake News blunder to rule them all. The media actively engaged their activism to fight ‘bad orange man’ at the cost of thousands of lives. Shame on them.
How does chloroquine work? Same way as it does for malaria. You see, malaria is this little parasite that enters the red blood cells and starts eating hemoglobin as its food source. The reason chloroquine works for malaria is the same reason it works for COVID-19 — while not fully understood, it is suspected to bind to DNA and interfere with the ability to work magic on hemoglobin. The same mechanism that stops malaria from getting its hands on hemoglobin and gobbling it up seems to do the same to COVID-19 (essentially little snippets of DNA in an envelope) from binding to it. On top of that, Hydroxychloroquine (an advanced descendant of regular old chloroquine) lowers the pH which can interfere with the replication of the virus. Again, while the full details are not known, the entire premise of this potentially ‘game changing’ treatment is to prevent hemoglobin from being interfered with, whether due to malaria or COVID-19.
No longer can the media and armchair pseudo-physicians sit in their little ivory towers, proclaiming “DUR so stoopid, malaria is bacteria, COVID-19 is virus, anti-bacteria drug no work on virus!”. They never got the memo that a drug doesn’t need to directly act on the pathogen to be effective. Sometimes it’s enough just to stop it from doing what it does to hemoglobin, regardless of the means it uses to do so.
Anyway, enough of the rant. What’s the end result here? First, the ventilator emergency needs to be re-examined. If you’re putting a patient on a ventilator because they’re going into a coma and need mechanical breathing to stay alive, okay we get it. Give ’em time for their immune systems to pull through. But if they’re conscious, alert, compliant — keep them on O2. Max it if you have to. If you HAVE to inevitably ventilate, do it at low pressure but max O2. Don’t tear up their lungs with max PEEP, you’re doing more harm to the patient because you’re treating the wrong disease.
Ideally, some form of treatment needs to happen to:

1. Inhibit viral growth and replication. Here plays CHQ+ZPAK+ZINC or other retroviral therapies being studies. Less virus, less hemoglobin losing its iron, less severity and damage.
2. Therapies used for anyone with abnormal hemoglobin or malfunctioning red blood cells. Blood transfusions. Whatever, I don’t know the full breadth and scope because I’m not a physician. But think along those lines, and treat the real disease. If you’re thinking about giving them plasma with antibodies, maybe if they’re already in bad shape think again and give them BLOOD with antibodies, or at least blood followed by plasma with antibodies.
3. Now that we know more about how this virus works and affects our bodies, a whole range of options should open up.
4. Don’t trust China. China is ASSHOE. (disclaimer: not talking about the people, just talking about the regime). They covered this up and have caused all kinds of death and carnage, both literal and economic. The ripples of this pandemic will be felt for decades.

Fini.

Would it be reasonable to assume then that the higher your red blood cell count the less likely to have severe illness? But then again, women tend to have lower blood cell counts than men yet are more protected from this virus. So then is iron toxicity playing a bigger role than hypoxia in severe illness? Are vegans and regular blood donors also protected from severe illness?

 

[theLaw]

 

[yerrag]

Would it be reasonable to assume then that the higher your red blood cell count the less likely to have severe illness? But then again, women tend to have lower blood cell counts than men yet are more protected from this virus. So then is iron toxicity playing a bigger role than hypoxia in severe illness? Are vegans and regular blood donors also protected from severe illness?

Optimal range for male RBC is 4. 2- 4.9

The higher the cell count, above optimal, the lower the blood volume. This is due to lower blood plasma volume, caused by low total sodium in the plasma, as sodium concentration in the plasma has to be maintained at a certain level. How much sodium is in the plasma is determined by the amount of albumin in plasma as albumin attracts sodium, and determines how much sodium is held on to in plasma.

However, a high serum RBC may not be due to low blood volume if the high RBC is due to abnormally high RBC. If the reticulocyte count is higher than 5% of RBC and if EPO (erythropoeitin) is also high, then abnormally high RBC is confirmed. And this can be due to the kidneys sensing poor oxygenation of tissue (either due to hypoxia or to hypoxemia) causing more RBC to be produced by the bone marrow as kidneys produce more EPO to signal more RBC to be produced.

 

[theLaw]

Just received word from a nurse in my family that in her hospital they are only putting patients on a ventilator as a last resort as they believe that it increases mortality.

 

[RealNeat]

I never said I had Coronavirus. Most likely I think h1n1 flu but who knows. I did get better then bacterial pneumonia set in. I did not just suddenly get worse. I had felt quite recovered before pneumonia which sets in really fast.

do you think you used the antibiotics at the wrong time? For example if you would heave started Losartan quickly then after symptoms went away you took the antibiotics the pneumonia might have not set in?

 

[ecstatichamster]

do you think you used the antibiotics at the wrong time? For example if you would heave started Losartan quickly then after symptoms went away you took the antibiotics the pneumonia might have not set in?

Perhaps. I had trouble getting the losartan so I couldn’t start it sooner.

I am not sure it was the right move taking the antibiotics so soon but I was really sick and hoping to take advantage of their anti-inflammatory qualities, and also pre-empt a bacterial infection, which clearly failed.

 

[Collden]

Looks like total mortality at least in Spain and Italy has now officially exceeded that of previous flu seasons.
EURO MOMO