md_a
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https://www.researchgate.net/public...ine_Phoshpdiesterase_Inhibitors_Acetazolamide
“Kidney disease, diabetes, pregnancy toxemia and retinal degeneration are probably the best known problems involving vascular leakage, but increasingly, cancer and heart disease are being recognized as consequences of prolonged permeability defects. Congestive heart failure and pulmonary hypertension commonly cause leakage of fluid into the lungs, and shock of any sort causes the lung to get "wet," a waterlogged condition called "shock lung." Simply hyperventilating for a couple of minutes will increase leakage from the blood into the lungs; hyperventilation decreases carbon dioxide, and increases serotonin and histamine. Hyperoxia itself contributes to lung injury, and exacerbates emphysema, though it is common to see patients breathing a high concentration of oxygen. Emphysema (which can be caused by hypothyroidism or hyper-estrogenism, and often can be cured by thyroid or progesterone) and many other respiratory problems are associated with capillary leakage. Cells of the lung and intestine are able to synthesize their own fibrin, apparently because of their special problems in preventing leakage. Prolonged systemic inflammation can lead to lung fibrosis, and fibrosis increases the likelihood of lung cancer.
The inflammatory state that causes exaggerated cellular permeability is very closely related to "hyperventilation," the loss of too much carbon dioxide. The release of serotonin during hyperventilation isn't the only cause of vascular leakage; the carbon dioxide itself is an essential factor in regulating the state of cellular electrons and in maintaining cellular integrity. Hyperventilation, like the shift from oxidative to glycolytic energy production that typifies estrogenized or stressed cells or cancer, raises intracellular pH. In the case of mast cells, increasing alkalinity causes them to release histamine (Alfonso, et al., 2005), but similar "alkaline-induced exocytosis" seems to occur in all stressed tissues.
The blood platelets that become incontinent and leak serotonin in the absence of carbon dioxide are undergoing the same structural stresses experience by endothelial cells, smooth muscle cells, mast cells and all other cells when carbon dioxide is depleted. Although it has been about 70 years since Yandell Henderson made it clear that supplemental oxygen should be combined with carbon dioxide, mechanical ventilation in hospitals is still causing lung injury resulting from hyperventilation, i.e., the absence of carbon dioxide. A similar misunderstanding of biology was involved in the use of dialysis to treat kidney disease. Until recently, commercial dialysis fluids contained acetate and/or racemic lactate instead of bicarbonate, because of the difficulty of preparing bicarbonate solutions, and the result was that very prolonged dialysis would damage the brain and other organs. (Veech and Gitomer, 1988, Veech and Fowler, 1987.) Dialysis has been seen to increase lung permeability Bell, et al., 1988).
Amyloidosis produced by chronic dialysis affects all organs, but its effects are best known in the brain, heart, kidneys, and lungs. Serum amyloid-A is one of the acute phase proteins, like C-reactive protein (CRP), that are produced by inflammation. Estrogen, radiation and other stresses increase those pro-inflammatory acute phase proteins, and decrease protective albumin, which is called a "negative acute phase protein," since it decreases when the other acute phase proteins increase. The liver is the major source of the acute phase proteins, and it is constantly burdened by toxins absorbed from the bowel; disinfection of the bowel is known to accelerate recovery from stress.
Seen from the perspective of the stress-leakage syndrome, any serious injury or sickness damages all organs. The exhaled breath is being used to diagnose inflammatory lung disease, since so many of the mediators of inflammation are volatile, but systemic diseases such as cancer and arthritis, and relatively minor stress can be detected by changes in the chemicals found in the breath. Polyunsaturated fats and their breakdown products--aldehydes, prostaglandins, isoprostanes, hydrocarbons, and free radicals--and carbon monoxide, nitric oxide, nitrite, and hydrogen peroxide are increased in the breath by most stresses. Both proline and glycine (which are major amino acids in gelatin) are very protective for the liver, increasing albumin, and stopping oxidative damage.
Saturated fats are protective against free radical damage and can reverse liver fibrosis. Thyroid hormone protects against excess estrogen, and can prevent or reverse fibrosis of the heart. Antiestrogens are widely effective against vascular leakage. Thyroid, progesterone, and testosterone are among the most effective natural antiestrogens, and they are curative in many conditions that involve vascular leakage. Progesterone and pregnenolone have been called the antifibromatic steroids, and it has been used to treat many inflammatory and fibrotic diseases, including cancer.
The antiserotonin drugs are being increasingly used to treat fibrotic diseases, and other problems related to vascular leakage.
Antiinflammatory and anticoagulant things, especially aspirin and vitamin E, protect against the accelerated turnover of fibrinogen/fibrin caused by estrogen and the various inflammatory states.”
Leakiness, aging, and cancer
“Mountain sickness” is a potentially deadly condition that develops in some people when they ascend too rapidly to a high altitude. Edema of the lungs and brain can develop rapidly, leading to convulsions and death. The standard drug for preventing it is acetazolamide, which inhibits carbonic anhydrase and causes carbon dioxide to be retained, creating a slight tendency toward acidosis. This treatment probably mimics the retention of carbon dioxide that occurs naturally in altitude adapted people. The reasons for mountain sickness, and the reasons for the low incidence of heart disease, cancer, cataracts, etc., at high altitude, offer clues to the prevention of death and deterioration from many other causes.”
Altitude and Mortality
“Increasing carbon dioxide lowers the intracellular pH, as well as inhibiting lactic acid formation, and restoring the oxidation of glucose increases CO2. Inhibiting carbonic anhydrase, to allow more CO2 to stay in the cell, contributes to intracellular acidification, and by systemically increasing carbon dioxide this inhibition has a broad range of protective anti-excitatory effects. The drug industry is now looking for chemicals that will specifically inhibit the carbonic anhydrase enzymes that are active in tumors. Existing carbonic anhydrase inhibitors, such as acetazolamide, will inhibit those enzymes, without harming other tissues. Aspirin has some effect as an inhibitor of carbonic anhydrase (Bayram, et al., 2008). Since histamine, serotonin (Vullo, et al., 2007), and estrogen (Barnett, et al., 2008; Garg, 1975) are carbonic anhydrase activators, their antagonists would help to acidify the hypoxic cells. Testosterone (Suzuki, et al., 1996) and progesterone are estrogen antagonists that inhibit carbonic anhydrase.” Ray Peat