709 lines
50 KiB
HTML
709 lines
50 KiB
HTML
<html>
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<head><title>Bleeding, clotting, cancer</title></head>
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<body>
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<h1>
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Bleeding, clotting, cancer
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</h1>
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<p>
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<em>The balance between bleeding and clotting is easily disturbed. The condensation and dissolution of the
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clotting protein, fibrinogen/fibrin, is a continuous process, sensitive to changes in stress, nutrition,
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and hormones. Clots form, locally or systemically, when fibrin is formed faster than it is dissolved.
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When fibrin is destroyed faster than it can be replaced, blood vessels become too permeable, and
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bleeding can occur more easily.</em>
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</p>
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<em>
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<p>
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Mental stress, exercise, estrogen, and serotonin activate both the formation and dissolution of clots.
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</p>
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<p>
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Bleeding and clotting are not only very closely related with each other, such that a given stress can
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induce either or both, but the condensation and dissolution of the clotting protein are involved in
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edema, multiple organ failure, and the growth of cancers. The growth of tumors is as directly related to
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the clotting system as are thromboses and hemorrhages.
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</p>
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<p>
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Disordered clotting contributes to maladaptive inflammation and to the "diseases" of aging and
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degeneration.
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</p>
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<p>
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Metabolic energy is the basic defense against the stress reactions that disrupt circulation, healing,
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and growth.
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</p>
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<p>
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"It is commonly known that the ESR (red cell sedimentation rate) of cancer patients is always high."
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</p>
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</em>
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<p>
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<em>
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"Thus far, completely unagglutinated blood has been found only in strictly healthy animals and men. No
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severely ill person has yet been seen who did not have intravascular agglutination of the blood and
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visibly pathologic vessel walls." Melvin H. Knisely, et al.<strong>, 1947</strong>)</em>
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</p>
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<hr />
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<p>
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When science became a sort of "profession," in the 19th century, the old "natural philosophy" of Newton"s
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time began to subdivide into many specialties. At that time, medicine had some general theories to account
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for deviations from good health, such as the theory of the four humors and their balance, but as those
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general theories disappeared, they weren"t replaced by any single scientific understanding of the nature of
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good health and disease. Medical education has convinced doctors and the public that the reasons for
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suffering, disability and death are mostly known, and that when medical experts agree to give a condition a
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name, there must be some clear scientific evidence behind that disease name.
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</p>
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<p>
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That mystique of diagnosing disease (specific, concrete, reified disease) was so strong that when Hans Selye
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noticed (in the 1930s) something that underlies all sickness (he first called it the "syndrome of being
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sick"), he was disregarded and disrespected, at least until his dangerous perceptions could be trimmed,
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distorted, and subsumed under some proper medical categories. <strong>Selye observed that stress causes
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internal bleeding (in lungs, adrenals, thymus, intestine, salivary and tear glands, etc.),</strong>
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but instead of trying to understand what that means for the control of sickness, the medical schools and
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journals have offered concrete, fragmentary, and false explanations for his observations. "Stomach acid"
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causes bleeding in the stomach and duodenum<strong>; </strong>
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stuff leaking out of the brain gets the blame for some cases of systemic bleeding, stuff leaking out of the
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uterus, for other cases, and so on. Selye"s observations have been rendered harmless (to medicine) by these
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falsely concrete explanations. While conventional medicine propagated its medical fantasies, it
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characterized Selye"s work as "controversial."
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</p>
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<p>
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In many cases, "diagnosis" consists of what could, at best, be called an educated guess, with no attempt to
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find evidence to support it. Obviously, if every doctor in the country is guessing wrong about certain
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deadly conditions, lots of people will die, and no one will see the need to even study the subject, since it
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has a definite name and an explanation that seems to satisfy.
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</p>
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<p>
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Instead of finding pseudo-reasons for the bleeding abnormalities caused by stress, it would be good to look
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freshly at the nature of blood and its circulation. It might turn out that it"s a way to expand our
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understanding of the stress reaction.
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</p>
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<p>
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Most people are aware of some of the variations of bleeding and clotting that occur commonly. Bleeding gums,
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nose-bleeds, menstruation and its variations, and the spontaneous bruising (especially on the thighs) that
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many women have premenstrually, are familiar events that don"t seem to mean much to the medical world.
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Sometimes nose-bleeds are clearly stress-related, but the usual "explanation" for that association is that
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high blood pressure simply blows out weak blood vessels. Bleeding gums are sometimes stress related, but
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high blood pressure is seldom invoked to explain that problem.
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</p>
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<p>
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The whole issue of blood vessel fragility is usually disposed of as a "genetic trait," or a result of old
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age. This is part of a general tendency to think of the blood vessels as an anatomically fixed,
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"congenital," and genetically determined system. At least until recently, nearly all physicians have called
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aneurysms "congenital defects." But varicose veins are merely low-pressure analogs of arterial aneurysms,
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and they obviously develop under specific conditions, such as pregnancy and malnutrition. Spider veins are
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another anatomical variation that commonly appears under the influence of estrogen. Subarachnoid
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hemorrhages, which can put pressure on the brain, are usually considered to result from a ruptured aneurysm,
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and these hemorrages are twice as common in women as in men, and probably result from a hormone imbalance.
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</p>
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<p>
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Menstrual bleeding is a good place to start the investigation of bleeding problems, since its relatively
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harmless abnormalities are physiologically related to some very serious health problems, such as pregnancy
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bleeding, abruptio placentae, and eclampsia. Women who die from eclampsia have been found to have massively
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clotted blood vessels in their brains, but the variety of names for the pregnancy disorders have prevented
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most people from thinking of pregnancy as a time when there is a high risk of the "thrombohemorrhagic
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disorders," a time when the clotting system is under stress. (For about fifteen years after Selye coined the
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term, only he and some Russians were publishing research on it, and Americans still don"t show much interest
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in the subject.)
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</p>
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<p>
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Women with a chronic menstrual problem resulting from progesterone deficiency often continue to bleed each
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month even when they are pregnant, and these women tend to develop toxemia, and to have a high incidence of
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pregnancy complications, and to deliver premature, poorly developed babies.
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</p>
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<p>
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In 1933 James Shute was recommending the use of vitamin E for preventing the clotting problems associated
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with pregnancy, that often lead to miscarriage. He based his work on animal studies, that led to vitamin E"s
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being known as the "fertility vitamin." Later, his sons Wilfred and Evan reported that vitamin E could
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prevent heart attacks, birth defects, complications of diabetes, phlebitis, hypertension, and some
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neurological problems.
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</p>
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<p>
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Later, referring to the decades of hostility of the medical establishment to vitamin E, Dr. Shute said
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"...an obstetrician was unduly hardy and audacious to try it." The spectrum of vitamin E"s protective
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effects (like those of aspirin) has been consistently misrepresented in the medical literature.
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</p>
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<p>
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Hematomas in many organs (pituitary, kidney, pancreas, liver, even around the abdominal muscles) can occur
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because of hormone imbalances in these difficult pregnancies. Tom Brewer"s demonstration that a good diet,
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with abundant protein, can prevent and cure pregnancy toxemia, is practically unknown in the medical world,
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though a protein deficiency has been shown to increase the risk of blood clots under many other
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circumstances besides pregnancy.
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</p>
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<p>
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Abruptio placentae (premature detachment of the placenta) has often been blamed on the use of vitamin E,
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because of vitamin E"s reputation for preventing abnormal clotting, though the evidence tends to suggest
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instead that vitamin E (like aspirin) reduces the risk of pregnancy-related hemorrhaging.
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</p>
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<p>
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One of the deadly clotting conditions related to childbirth has been called "pregnancy anaphylaxis," but it
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is more often called "amniotic fluid embolism," despite the fact that amniotic fluid injected intravenously
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is harmless (Petroianu, et al.), and only by grinding up and injecting massive amounts of the pregnancy
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membranes can the clotting system be disturbed. The term is really a criminal misnomer, serving to blame a
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preventable clotting/shock disorder on the patient.
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</p>
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<p>
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<strong>"Consumption coagulopathy" refers to the bleeding that follows excessive activation of the clotting
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system,</strong> combined with a defensive dissolving of the clots, when finally the fibrinogen or other
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elements of the clotting system have been depleted, consumed. A blood test can show when clot degradation
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products are being produced too rapidly, even while a person has no symptoms, so there should be time for
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the accelerated clotting to be controlled, before major thromboses and bleeding and shock have developed.
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</p>
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<p>
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In 1936 Albert Szent-Gyorgyi reported that some chemicals in lemon juice, which he called vitamin P (or
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citrin), would prevent purpura, subcutaneous capillary bleeding. By 1938, he had decided that citrin, (which
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he now called bioflavonoid) probably wasn"t a vitamin, and that its action was more like that of a drug,
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substituting for a natural regulatory factor that was missing. Later research has confirmed that view,
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showing that the bioflavonoids inhibit the enzyme hyaluronidase, which degrades the "ground substance" of
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connective tissues. At least one natural endogenous inhibitor of hyaluronidase has now been identified. The
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basement membrane that surrounds and unites the endothelial cells of capillaries is largely hyaluronic acid
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and collagen. It isn"t thrombogenic (Buchanan, et al.), despite the common belief that collagen is
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intrinsically a clot instigator. The breakdown of this ground substance is involved in growth and
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reproduction, so an excess of bioflavonoids in the diet could conceivably interfere with fertility and fetal
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development. Some bioflavonoids have been prescribed for menstrual problems, and are probably useful when
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the physiological inhibitor isn"t adequate.
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</p>
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<p>
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Hyaluronidase is activated by shock, and also by estrogen. Both hyaluronidase and estrogen have been used in
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plastic surgery to "expand" tissue, weakening it and allowing it to be enlarged. During aging, hyaluronic
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acid (the major water-retaining component of connective tissue that"s broken down by hyaluronidase)
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decreases in the connective tissues, but increases in the blood stream. Shock allows hyaluronic acid to
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increase in the serum. Fragments of degraded hyaluronic acid are pro-inflammatory.
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</p>
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<p>
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In the 1940s Hans Selye studied the steroid hormones in a comprehensive way, defining their actions and
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interactions. At that time he found that progesterone protected broadly against stress, and that a large
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dose of estrogen created a condition that duplicated the initial shock phase of the stress reaction. Later
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animal studies showed that estrogen quickly causes enlargement of the adrenal glands, followed by bleeding,
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and, with large and continuous doses, death of the adrenal cells.
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</p>
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<p>
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Estrogen promotes vascular permeability by a variety of mechanisms. Serotonin, histamine, lactic acid, and
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various cytokines and prostaglandins contribute to the leakage stimulated by estrogen, trauma, irradiation,
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poisoning, oxygen deprivation, and other factors that can induce shock. Even exercise, mental stress, and
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aging can increase the tendency of capillaries to leak.
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</p>
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<p>
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Progesterone and cortisol protect against shock and stress partly by maintaining the resistance and
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integrity of the capillaries, preventing leakage of blood materials into the tissues. The maintenance of the
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capillary barrier probably also prevents substances from the extracellular matrix from triggering the
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clotting systems.
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</p>
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<p>
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Clots are formed when soluble fibrinogen polymerizes, condenses, and becomes insoluble. Even before the
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particles of fibrin become insoluble, a clot-dissolving system is continuously breaking it down into small
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peptides. These peptides tend to cause capillaries to leak. If a massive amount of fibrinogen and fibrin
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leak out of capillaries, clots are formed outside capillaries, and the peptides released in the process of
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cleaning up this debris contribute to further leakage, and to inflammation. The inflammation stimulates the
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production of collagen-rich connective tissue, and a fibrotic tissue replaces the functional tissues. Many
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of Hans Selye"s experiments explored the conditions in which inflammation, exudation, and fibrosis
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developed, sometimes ending with calcification of the region.
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</p>
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<p>
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The presence of fibrin in the extracellular matrix interferes with the differentiated functioning of cells,
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which depend on their contact with a normal matrix. When healing and regeneration occur in the normal
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matrix, the remodeling of the tissue involves the breakdown of collagen, which releases peptides with
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antiinflammatory, antiangiogenic and antiinvasive actions. When fibrin is present, the remodeling process
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releases peptides that increase cell growth, invasiveness, inflammation, and the production of new blood
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vessels, which in turn become leaky.
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</p>
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<p>
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Leakage of fluid out of the blood is one of the main features of shock, and at first it is mainly the loss
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of water and volume that creates a problem, by reducing the oxygenation of tissue and increasing the
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viscosity of the remaining blood. Blood becomes more concentrated during strenuous exercise, during the
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night, and in the winter, increasing the viscosity, and increasing the risk of strokes and other thrombotic
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problems. The absence of light causes the metabolic and hormonal changes typical of stress.
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</p>
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<p>
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Tom Brewer and his associates showed that pregnancy toxemia involves inadequate blood volume, and that using
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extra sodium can alleviate the symptoms, including preventing albuminuria, one of the most characteristic
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signs of toxemia/preeclampsia. (Besides causing loss of albumin through leaky capillaries, estrogen also
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inhibits its synthesis by the liver<strong>; </strong>
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the loss of colloid osmotic pressure in hypoalbuminemia has many consequences, including disturbances of
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blood lipids.) Estrogen"s action in toxemia of pregnancy is paralleled by the fact that blood viscosity is
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highest at the time of ovulation during the normal monthly cycle.
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</p>
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<p>
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In the healthy person, some of the fibrin that is constantly being formed is deposited on the inside of
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blood vessels (and on the surfaces of blood cells), and this layer forms an important part of the
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capillary"s resistance to leaking. A.L. Copley, who pioneered the study of hemorrheology, called this the
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"endoendothelial layer." This layer probably contains albumin, too, in close association with the
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(carbohydrate) "glycocalyx" of the endothelial cell surface. Disturbances that accelerate the formation and
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dissolution of the fibrin layer can be detected by an increase in the concentration of the fibrin
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degradation products (FDP, or D-dimers) in the blood, even before any symptoms have appeared.
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</p>
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<p>
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Although Selye described shock as the first (potentially lethal) phase of stress, usually followed by the
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corrective adaptive processes, it"s useful to think of aging in terms of a lingering partial state of shock,
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in which adaptation is less than perfect.
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</p>
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<p>
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The loss of blood volume through leaky capillaries tends to be self-aggravating. The concentrated and
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viscous blood doesn"t flow as well through the capillaries, and this energy deprivation leads to increased
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leakiness of the cells, and to swelling of the endothelial cells, decreasing the internal diameter of the
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small blood vessels. The energy-deprived state increases lactic acid, adrenaline, and free fatty acids, all
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of which contribute to increased leakiness and impaired circulation.
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</p>
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<p>
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In the bowel, the capillary malfunction increases the absorption of endotoxin, which intensifies the
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systemic energy problem. (Polyunsaturated oils, especially fish oil, damage the bowel capillaries, allowing
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more endotoxin to be absorbed.)
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</p>
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<p>
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In the uterus, increased viscosity of the blood impairs the delivery of oxygen and nutrients to the fetus,
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retarding its development. Dilution of the blood under the influence of progesterone reduces the hematocrit,
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helping to compensate for the viscosity<strong>;</strong> in toxemic pregnancies this isn"t sufficient to
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maintain normal viscosity and perfusion.
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</p>
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<p>
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In the brain, hyperviscosity contributes to dementia. In the lung, to edema and reduced oxygenation ("shock
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lung," "wet lung," respiratory distress<strong>; </strong>this lung edema is a major cause of mortality in
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pregnancy). In the pancreas, to inflammation, and to the release of proteolytic enzymes, impairing the
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clotting system even more.
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</p>
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<p>
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During the development of cancer, hyperviscosity (and the associated hypoxia) contributes to the tumor"s
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deranged metabolism, tending to increase its production of ammonia, clotting factors, and other
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stress-inducing toxins.
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</p>
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<p>
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Factors that increase the fluidity of the blood protect against all of the thrombohemorrhagic conditions,
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and are especially protective against the estrogen-promoted cancers. Progesterone decreases the production
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of fibrinogen, and increases the volume of the blood and the flexibility of the red blood cells, increasing
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the ability of blood to flow freely, and it also decreases the leakiness of capillaries. Hypothyroid people
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(who tend to have low progesterone and high estrogen) are highly susceptible to heart disease and cancer,
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and have abnormally viscous blood. Hyperthyroid people have unusually fluid blood. Hypothyroidism increases
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the leakiness of capillaries, and decreases the amount of albumin in the blood. Albumin itself decreases the
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permeability of blood vessels.
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</p>
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<p>
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In hypothyroidism and under the influence of estrogen, there is a chronic increase of free fatty acids, and
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the free fatty acids are an important factor in increasing the production of fibrinogen (Pickart), and in
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blocking fibrinolysis (Lindquist, et al.). If the body"s stores of fat are largely polyunsaturated fats, the
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free fatty acids will combine with the fibrin as it polymerizes, making the clots especially resistant to
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dissolution.
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</p>
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<p>
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In the 1940s, Melvin Knisely noticed that all seriously sick people had "sludged" blood, that can be
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observed microscopically in the small blood vessels on the surface of the person"s eye. The cells tend to
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stick together, producing a sludgy appearance and slow flow. This probably corresponds to increased
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viscosity of the plasma, increased red cell sedimentation rate, increased fibrinogen, decreased albumin, and
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decreased thyroid and progesterone. Clumped red cells, when separated under the microscope, appear to be
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bound together by fine filaments, possibly of fibrin.
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</p>
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<p>
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Aspirin is known to have a variety of anticancer activities, including the prevention of metastasis, and
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some people have reasoned that the clotting process simply helps migrating cancer cells to become anchored.
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However, the clotting process is normally part of the healing and repair processes, and I think the role of
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the fibrin clotting system in cancer is that the breakdown products of fibrin are growth-promoters, and that
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their presence in the extracellular matrix in large quantity, distorting the normal composition of the
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matrix, is what causes the formation of a tumor. It"s the leakage of the fibrin into the extracellular
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matrix that leads to the development of tumors.
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</p>
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<p>
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Heparin, a natural anticoagulant, is currently being tested as an anticancer agent.
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</p>
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<p>
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All of the factors that promote stable oxidative energy production protect against the coagulative
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derangements, largely by preventing capillary leakage, and it now seems that these processes protect against
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cancer as well as protecting against all of the stress-related degenerative and inflammatory diseases.
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</p>
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<p>
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Since hyperventilation can increase capillary leakage and cause the blood to become more concentrated,
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breathing carbon dioxide (breathing in a bag) should help to restore capillary function.
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</p>
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<p>
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Since the blood becomes more concentrated, viscous, and clottable during the night (especially during long
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winter nights), the risk of a heart attack or stroke would probably be reduced by drinking orange juice
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before getting out of bed (and at bed-time), to dilute the blood and decrease adrenaline and the free fatty
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acids, which contribute to the increased tendency to form clots in the morning. (Assanelli, et al., discuss
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the importance of adrenaline in morning/winter sudden death; Antoniades and Westmoreland show that the
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availability of glucose can override major promoters of clotting and bleeding.)
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</p>
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<p>
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<strong>Things to reduce the stress-related coagulopathies:</strong> Sugar and niacin to minimize the
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liberation of fatty acids, progesterone and thyroid to protect against estrogen and to avoid hypoglycemia
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(which increases adrenaline and free fatty acids and accelerates clotting), magnesium and gelatin (or
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glycine), to protect against intracellular calcium overload and hypoxia, and vitamin E and salicylic acid
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for antiinflammatory effects, are major nutrients that protect the circulatory system against clotting,
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bleeding, edema, and tumefaction.
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</p>
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<p>
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Even on the mornings that you don"t drop dead, there is reduced adaptive capacity and functional impairment
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before eating breakfast. For example, men who went for a run before breakfast were found to have broken
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chromosomes in their blood cells, but if they ate breakfast before running, their chromosomes weren"t
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damaged.
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</p>
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<hr />
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<p><strong><h3>REFERENCES</h3></strong></p>
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<p>
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Vet Rec. 1988 Apr 2;122(14):329-32. <strong>Relationships between the erythrocyte sedimentation rate, plasma
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proteins and viscosity, and leucocyte counts in thoroughbred racehorses.</strong> Allen BV. "The
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influence of plasma proteins on erythrocyte aggregation was studied in a population of young thoroughbred
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racehorses, using the 60 minute erythrocyte sedimentation rate (ESR) with and without haematocrit
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standardisation. The ESR<strong>
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was correlated inversely with the haematocrit,</strong>
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<strong>
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but directly with fibrinogen, plasma viscosity and serum total globulins.
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</strong>When ESR values were standardised to a common haematocrit the correlation coefficients for the same
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plasma protein factors were increased. Albumin levels showed a strong direct relationship with<strong>
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haematocrit which accounted for the inverse correlation found between albumin and ESR.
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</strong>
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<hr />
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</p>
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<p>
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Ann N Y Acad Sci. 1976;275:28-46. <strong>Metabolic influences in experimental thrombosis.</strong>
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Antoniades HN, Westmoreland N. Studies presented in this report demonstrate that intravascular coagulation
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and thrombosis in the whole animal can be greatly influenced by noncoagulation factors, such as metabolic,
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endocrinologic, and nutritional states. <strong>Injection of a partially purified human serum procoagulant
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fraction produced no significant clotting abnormalities in normal fed rats; however, injection of an
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identical preparation in fasted, diabetic, and obese rats produced hypercoagulability of blood,
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thrombosis, and hemorrhage.</strong>
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<strong>Glucose injection in fasted rats and insulin injection in diabetic rats reversed their
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susceptibility to thrombosis.</strong> The concentrations of serum free fatty acids were shown to be
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elevated in the susceptible animals; however, they returned to normal in fasted and diabetic rats after
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injections of glucose and insulin, respectively. Infusion of free fatty acid-albumin preparations in normal
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fed rats rendered the animals susceptible to thrombosis when challenged with the serum procoagulant
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fraction.
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|
</p>
|
|
|
|
<p>
|
|
Cardiologia. 1997 Jul;42(7):729-35.<strong>
|
|
[Circadian variation of sudden cardiac death in young people with and without coronary disease]</strong>
|
|
Assanelli D, Bersatti F, Turla C, Restori M, Amariti ML, Romano A, Ferrari M. "To clarify whether sudden
|
|
cardiac death has a circadian rhythm in young people we have studied 40 patients < 45 years who died in
|
|
Brescia between 1984 and 1993 of sudden cardiac death showing at autopsy features of coronary artery disease
|
|
(CAD) and 12 patients aged < 30 years who died of sudden cardiac death without autoptic features of CAD.
|
|
We observed a circadian rhythm in the hours of the morning in the two groups, more evident in patients
|
|
without CAD. In patients<strong>
|
|
with autoptic features of CAD, we also observed a higher rate of events during the winter months. We
|
|
would like to stress the importance of the adrenergic</strong> system as a trigger able to produce the
|
|
event."
|
|
</p>
|
|
<p>
|
|
An R Acad Nac Med (Madr). 2002;119(1):163-73; discussion 173-4. <strong>[HELLP syndrome and hemorrhagic
|
|
gestosis]</strong> Botella Llusia J. In the year 1817, Charlotte daughter of Georges IV and princess of
|
|
Wales, died on an unknown condition with uteroplacental hemorrhage <strong>
|
|
and fetal death called at the time "Uteroplacental Apoplexy" and later "Abruptio Placentae". This
|
|
affection was described in the classical books as an hemorrhagic complication of labor. In 1961 we have
|
|
at first related the Abruptio with acute toxemia (preeclampsia) and have proposed the term "Gestosis
|
|
hemorragica" to design
|
|
</strong>
|
|
it. In 1982 Weinstein has described the called HELLP syndrome (Hemolysis, Elevated liver Enzymes, at Low
|
|
Platelets) which basically is the same pathological picture as the described by us as "hemorrhagic toxemia".
|
|
The aim of the paper is to demonstrate the identity of both syndromes and to claim for the priority of our
|
|
definition.
|
|
</p>
|
|
<p>
|
|
Thromb Haemost. 1987 Aug 4;58(2):698-704. <strong>The basement membrane underlying the vascular endothelium
|
|
is not thrombogenic: in vivo and in vitro studies with rabbit and human tissue.</strong> Buchanan MR,
|
|
Richardson M, Haas TA, Hirsh J, Madri JA.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H1028-34. Epub 2002 Nov 21. <strong>Endotoxemia stimulates
|
|
skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.</strong>
|
|
Bundgaard H, Kjeldsen K, Suarez Krabbe K, van Hall G, Simonsen L, Qvist J, Hansen CM, Moller K, Fonsmark L,
|
|
Lav Madsen P, Klarlund Pedersen B.
|
|
</p>
|
|
<p>
|
|
Thromb Haemost. 2001 Jul;86(1):334-45.<strong>
|
|
Tissue factor--a</strong>
|
|
<strong>
|
|
receptor involved in the control of cellular properties, including angiogenesis.</strong> Chen J,
|
|
Bierhaus A, Schiekofer S, Andrassy M, Chen B, Stern DM, Nawroth PP. <strong>"Tissue factor (TF), the major
|
|
initiator of blood coagulation, serves as a regulator of angiogenesis, tumor growth and
|
|
metastasis.</strong>"
|
|
</p>
|
|
|
|
<p>
|
|
Thromb Res Suppl. 1983;5:105-45. <strong>The physiological significance of the endoendothelial fibrin lining
|
|
(EEFL) as the critical interface in the 'vessel-blood organ' and the importance of in vivo 'fibrinogenin
|
|
formation' in health and disease.</strong> Copley AL. "The author's theory of the <strong
|
|
>endoendothelial fibrin lining (EEFL) . . .
|
|
</strong>localizes the homeostasis between steady fibrin formation and deposition, or 'fibrination', and
|
|
continuous fibrinolysis in the more or less immobile portion of the plasmatic zone next to the vessel wall.
|
|
In 1971, the author advanced, in relation to the EEFL, the theory of <strong>fibrinogen gel clotting without
|
|
thrombin action or 'fibrinogenin' formation in vivo.</strong>" "The EEFL of the vessel-blood organ is
|
|
considered by the author as the crucial critical interface between the blood and the vessel wall. <strong>It
|
|
is the primary barrier, followed by the endothelium (comprising the endothelial cells and the
|
|
interendothelial cement substance which contains or is identical with 'cement fibrin') and the basement
|
|
membrane for the exchanges between the blood, the vessel wall and its surrounding tissues and spaces.
|
|
The EEFL acts as anticoagulant, is antithrombogenic, maintains vascular patency and aids cardiac action
|
|
by decreasing significantly the apparent viscosity of blood,</strong> referred to in the literature as
|
|
the 'Copley-Scott Blair phenomenon'. A new concept of leukocyte emigration traversing the capillary wall is
|
|
presented, affecting focal fibrinolysis of the EEFL and of fibrin contained in the interendothelial cement
|
|
substance and in the basement membrane. The physical property of capillary (or vascular) permeability is
|
|
related to the existence of the EEFL, since, as found by Copley et al, both fibrinopeptides, liberated in
|
|
the transition of fibrinogen to fibrin, and plasminopeptides, freed in the conversion of plasminogen to
|
|
plasmin, enhance capillary permeability. Capillary fragility, which is antagonistic to capillary
|
|
permeability, is in great part due to fibrinolytic action on fibrin as a constituent of the basement
|
|
membrane."
|
|
</p>
|
|
<p>
|
|
Am J Obstet Gynecol. 1995 Apr;172(4 Pt 1):1291-8. <strong>Blindness associated with preeclampsia and
|
|
eclampsia.</strong> Cunningham FG, Fernandez CO, Hernandez C.
|
|
</p>
|
|
|
|
<p>
|
|
East Afr Med J. 2002 Apr;79(4):181-3<strong>. Haemorheological changes during the menstrual cycle.</strong>
|
|
Dapper DV, Didia BC.
|
|
</p>
|
|
<p>
|
|
Cancer Res. 2001 Feb 1;61(3):795-8. <strong>
|
|
Tumor hypoxia,</strong>
|
|
<strong>
|
|
the physiological link between Trousseau's syndrome (carcinoma-induced coagulopathy) and
|
|
metastasis.</strong> Denko NC, Giaccia AJ.
|
|
</p>
|
|
<p>
|
|
Lab Invest 1998 Jun;78(6):657-68. <strong>Development of porous defects in plasma membranes of adenosine
|
|
triphosphate-depleted Madin-Darby canine kidney cells and its inhibition by glycine.</strong> Dong Z,
|
|
Patel Y, Saikumar P, Weinberg JM, Venkatachalam MA
|
|
</p>
|
|
|
|
<p>
|
|
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2692-7. <strong>Seasonal variations of rheological and
|
|
hemostatic parameters and acute-phase reactants in young, healthy subjects.</strong> Frohlich M, Sund M,
|
|
Russ S, Hoffmeister A, Fischer HG, Hombach V, Koenig W.
|
|
</p>
|
|
<p>
|
|
Respir Physiol Neurobiol. 2003 Oct 16;138(1):37-44. <strong>Lactate as a modulator of hypoxia-induced
|
|
hyperventilation.</strong>Gargaglioni LH, Bicego KC, Steiner AA, Branco LG.
|
|
</p>
|
|
<p>
|
|
Am J Vet Res. 1994 Jun;55(6):854-61.<strong>
|
|
Hemorheologic</strong>
|
|
<strong>
|
|
alterations induced by incremental treadmill exercise in Thoroughbreds.
|
|
</strong>
|
|
|
|
Geor RJ, Weiss DJ, Smith CM.
|
|
</p>
|
|
<p>
|
|
Vopr Pitan. 1995;(1):7-11. <strong>[Effects of dietary fat on permeability of the protective intestinal
|
|
barrier to</strong>
|
|
</p>
|
|
<p><strong>macromolecules in experimental anaphylaxis]</strong>[Article in Russian]</p>
|
|
<p>
|
|
Gmoshinskii IV, Ermekpaeva RA, Lysikov IuA, Kulakova SN, Mazo VK, Morozov IA.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Cell Physiol 2000 Nov;279(5):C1495-505. <strong>Calcium regulates estrogen increase in
|
|
permeability of cultured CaSki epithelium by eNOS-dependent mechanism.</strong> Gorodeski GI.
|
|
</p>
|
|
|
|
<p>
|
|
J Reprod Med. 2002 Dec;47(12):1021-4. <strong>Documentation of amniotic fluid embolism via lung
|
|
histopathology. Fact or Fiction?
|
|
</strong>
|
|
Hankins GD, Snyder R, Dinh T, Van Hook J, Clark S, Vandelan A.
|
|
</p>
|
|
<p>
|
|
Klin Wochenschr. 1990 Jun 5;68(11):559-64. <strong>
|
|
[Hemodynamic and hemorheologic findings in patients with pregnancy-induced hypertension: comparison of
|
|
pre-eclampsia and chronic hypertension]</strong>
|
|
Heilmann L, Schmid-Schonbein H.
|
|
</p>
|
|
<p>
|
|
Zentralbl Gynakol. 1986;108(7):393-402. <strong>
|
|
[Changes in flow properties of the blood in pregnancy]</strong> Heilmann L.
|
|
</p>
|
|
<p>
|
|
Eur J Vasc Surg. 1992 Jan;6(1):36-40. <strong>Claudication induces systemic capillary endothelial
|
|
swelling.</strong> Hickey NC, Hudlicka O, Simms MH.
|
|
</p>
|
|
<p>
|
|
Blood. 2001 Mar 15;97(6):1697-702.<strong>
|
|
Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat
|
|
aortic endothelial cells.</strong> Kawano H, Tsuji H, Nishimura H, Kimura S, Yano S, Ukimura N, Kunieda
|
|
Y, Yoshizumi M, Sugano T, Nakagawa K, Masuda H, Sawada S, Nakagawa M.
|
|
</p>
|
|
|
|
<p>
|
|
Br Med J (Clin Res Ed). 1984 Nov 24;289(6456):1405-8.<strong>
|
|
Increases in platelet and red cell counts, blood viscosity, and arterial pressure during mild surface
|
|
cooling: factors in mortality from coronary and cerebral thrombosis in winter.</strong> Keatinge WR,
|
|
Coleshaw SR, Cotter F, Mattock M, Murphy M, Chelliah R.<strong>
|
|
"Six hours of mild surface cooling in moving air at 24 degrees C with little fall in core temperature
|
|
(0.4 degree C) increased the packed cell volume by 7% and increased the platelet count and usually the
|
|
mean platelet volume to produce a 15% increase in the fraction of plasma volume occupied by platelets.
|
|
Little of these increases occurred in the first hour. Whole blood viscosity increased by 21%; plasma
|
|
viscosity usually increased, and arterial pressure rose on average</strong> from 126/69 to 138/87 mm
|
|
Hg."
|
|
</p>
|
|
<p>
|
|
Acta Chir Scand. 1976;142(1):20-5. <strong>Induction of endogenous fibrinolysis inhibition in the dog.
|
|
Effect of intravascular coagulation and release of free fatty acids.</strong> Lindquist O, Bagge L,
|
|
Saldeen T. "In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was
|
|
observed. The role of this increase for the development <strong>of fibrinolysis inhibition was tested by
|
|
infusion of norepinephrine alone and in combination with nicotinic acid. Norepinephrine caused an
|
|
increase of FFA after 2 hours and in urokinase inhibitor activity after 24-48 hours.</strong>
|
|
|
|
Both of these were diminished by high doses of nicotinic acid, indicating that the release of FFA rather
|
|
than intravascular coagulation might be the principal mechanism underlying the occurrence of fibrinolysis
|
|
inhibition following trauma."
|
|
</p>
|
|
<p>
|
|
Matrix Biol. 2002 Jan;21(1):31-7. <strong>Inhibitors of the hyaluronidases.</strong> Mio K, Stern R.
|
|
"Because of increased interest in hyaluronidases and their hyaluronan substrate, a study of these inhibitors
|
|
was undertaken recently. <strong>The predominant serum inhibitor is magnesium-dependent....</strong>"
|
|
</p>
|
|
<p>
|
|
Vopr Onkol. 1991;37(9-10):992-7. <strong>[Blood coagulation disorders and tumor growth]</strong>[Article in
|
|
Russian] Mkrtchian LN, Shukurian SG, Sarkisian OM, Magakian AG, Khachaturova TS, Ambartsumian AM.
|
|
</p>
|
|
<p>
|
|
Usp Fiziol Nauk. 1989 Oct-Dec;20(4):94-109. <strong>[The physiologic coagulation fibrinolytic system of the
|
|
body and
|
|
</strong>
|
|
<strong>thrombohemorrhagic theory in oncology]</strong> [Article in <strong>Russian</strong>] Nadiradze ISh,
|
|
Machabeli MS.
|
|
</p>
|
|
|
|
<p>
|
|
Arch Gynecol Obstet. 2002 Nov;267(1):7-10. <strong>Sex hormones, hemostasis and early pregnancy
|
|
loss.</strong> Nelson DB, Ness RB, Grisso JA, Cushman M. "This study was designed to determine the
|
|
association between coagulation factors and spontaneous abortion adjusting for sex steroids and to examine
|
|
the influence of sex hormones on coagulation factors early in pregnancy." "The relationship between
|
|
coagulation factors and spontaneous abortion was reduced after adjustment for progesterone suggesting that
|
|
<strong>progesterone mediates the relationship between low levels of coagulation factors and spontaneous
|
|
abortion. Progesterone seems to be the primary marker for a spontaneous abortion among women seeking
|
|
emergent care.</strong>"
|
|
</p>
|
|
<p>
|
|
Toxicol Pathol. 1992;20(1):71-80. <strong>
|
|
Pathogenesis of blood-filled cavities in estrogen-induced anterior pituitary tumors in male
|
|
Sprague-Dawley rats.</strong> van Nesselrooij JH, Hendriksen GJ, Feron VJ, Bosland MC.
|
|
</p>
|
|
<p>
|
|
Arch Int Physiol Biochim. 1983 Jul;91(2):81-5. <strong>Effects of the administration of progesterone and
|
|
adrenal medullectomy on the plasma fibrinogen levels in rats with surgical injury (laparotomy).</strong>
|
|
Palma JA, Gavotto AC, Villagra SB.
|
|
</p>
|
|
|
|
<p>
|
|
Pediatr Crit Care Med. 2000 Jul;1(1):65-71. <strong>Administration of autologous fetal membranes: Effects on
|
|
the coagulation in pregnant mini-pigs.</strong>
|
|
Petroianu GA, Toomes LM, Maleck WM, Friedberg C, Bergler WF, Rufer R. "<strong>A hallmark of the so-called
|
|
amniotic fluid embolism is the induction of coagulation defects. Entry of meconium-free autologous
|
|
amniotic fluid into the circulation, however, is innocuous.</strong>" "Animals received 2 g FM [fetal
|
|
membranes] (shredded and suspended in lactated Ringer's solution) via an ear vein. <strong>
|
|
However, the full clinical picture of amniotic fluid embolism and disseminated intravascular coagulation
|
|
could not be elicited despite the high dose of FM used.</strong>"
|
|
</p>
|
|
<p>
|
|
Am J Physiol. 1976 Apr;230(4):996-1002. <strong>Free fatty acids and albumin as mediators of
|
|
thrombin-stimulated fibrinogen synthesis.</strong>
|
|
|
|
Pickart LR, Thaler MM. "Mobilization of FFA in mice, triggered with an injection of thrombin, was followed
|
|
within 24 h by a 2.5-fold increase in fibrinogen synthesis and a 30% increase in plasma fibrinogen
|
|
concentration." "Injection of exogenous defatted albumin into mice before thrombin injection prevented the
|
|
FFA-associated rise in fibrinogen synthesis and plasma concentration." "These studies indicate that the
|
|
FFA/ALBUMIN RATIO MAY PLAY A MAJOR ROLE IN THE REPLENISHMENT OF FIBRINOGEN AFTER PERIODS OF RAPID
|
|
DEFIBRINOGENATION."
|
|
</p>
|
|
<p>
|
|
Thromb Haemost. 1995 Jul;74(1):391-5. <strong>Tissue factor expression in human leukocytes and tumor
|
|
cells.</strong> Rickles FR, Hair GA, Zeff RA, Lee E, Bona RD. <strong>"Tissue factor (TF) exists in a
|
|
cryptic form [i.e. without procoagulant activity (PCA)] in peripheral blood monocytes and quiescent
|
|
tissue macrophages but is expressed constitutively in most human tumor cells."</strong> "The regulation
|
|
of TF synthesis in cells is complex and new information from transfection studies suggests that changes in
|
|
cellular glycosylation pathways impair cell surface expression of functional TF." "The importance of
|
|
carbohydrate modification of TF is reviewed."
|
|
</p>
|
|
<p>
|
|
Nature 138: 32 (1936). Selye, H. <strong>A Syndrome produced by diverse nocuous agents.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Int J Microcirc Clin Exp. 1996 Sep-Oct;16(5):266-70. <strong>Hyperventilation enhances transcapillary
|
|
diffusion of sodium fluorescein.</strong> Steurer J, Schiesser D, Stey C, Vetter W, Elzi MV, Barras JP,
|
|
Franzeck UK.
|
|
</p>
|
|
<p>
|
|
Lancet. 1991 Jul 6;338(8758):9-13. <strong>Seasonal variations in fibrinogen concentrations among elderly
|
|
people.</strong> Stout RW, Crawford V. "Mortality and morbidity in elderly people are higher in winter
|
|
than in summer months, with seasonal variations in rates of both fatal and non-fatal myocardial infarction
|
|
and stroke." "Significant seasonal effects were found for fibrinogen, plasma viscosity, and HDL cholesterol
|
|
(p less than 0.003, Bonferroni adjustment). Plasma fibrinogen concentrations showed the greatest seasonal
|
|
change and were 23% higher in the coldest six months compared with summer months. Fibrinogen was
|
|
significantly (p less than 0.05) and negatively related to core body temperature and all measures of
|
|
environmental temperature." "Those living in institutions had greater changes in plasma fibrinogen than
|
|
those living in the community. The seasonal variation in plasma fibrinogen concentration is large enough to
|
|
increase the risk of both myocardial infarction and stroke in winter."
|
|
</p>
|
|
<p>
|
|
Akush Ginekol (Mosk). 1989 Jan;(1):43-6. <strong>[Coagulative activity of the amniotic fluid]</strong>
|
|
[Article in <strong>Russian</strong>] Tersenov OA, Mikhaleva IV, Usol'tseva VA, Byshevskii Ash. "An
|
|
ultracentrifugation study has shown thromboplastin to be the only blood coagulating agent, present in the
|
|
amniotic fluid (AF).<strong>
|
|
Its AF level shows no correlation to the rate of intrapartum or early postpartum thrombohemorrhagic
|
|
complications...."</strong>
|
|
</p>
|
|
<p>
|
|
Metabolism. 1989 May;38(5):471-8. <strong>
|
|
Effects of hypothyroidism on vascular 125I-albumin permeation and blood flow in Rats.</strong> Tilton
|
|
RG, Pugliese G, Chang K, Speedy A, Province MA, Kilo C, Williamson JR. "Effects of hypothyroidism on
|
|
vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley
|
|
rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy."
|
|
"After 10 to 12 weeks of thiouracil treatment, <strong>125I-albumin permeation was increased significantly
|
|
in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue</strong
|
|
>...."
|
|
</p>
|
|
<p>
|
|
Clin Nutr. 2001 Aug;20(4):351-9. <strong>Effect of eicosapentaenoic acid (EPA) on tight junction
|
|
permeability in intestinal monolayer cells.</strong> Usami M, Muraki K, Iwamoto M, Ohata A, Matsushita
|
|
E, Miki A.
|
|
</p>
|
|
|
|
<p>
|
|
Carcinogenesis. 2003 Jun;24(6):1009-13. Epub 2003 Mar 28. <strong>Tissue factor signal
|
|
</strong>
|
|
<strong>transduction in angiogenesis.</strong> Versteeg HH, Peppelenbosch MP, Spek CA. <strong>Tissue factor
|
|
(TF), a 47-kDa transmembrane glycoprotein, is a principal regulator of oncogenic neoangiogenesis and
|
|
controls therefore the cancerous process.
|
|
</strong>
|
|
Although originally identified as a component of the coagulation cascade, it has become clear that TF
|
|
functions as a cytokine-like receptor and this notion was confirmed by the discovery of
|
|
coagulation-independent actions of TF (which include regulation of tumour growth, embryonic and oncogenic
|
|
blood vessel formation as well as regulation of inflammation and sepsis). In accordance, TF-mediated signal
|
|
transduction events are readily detected and the elucidation of the underlying molecular mechanisms has
|
|
recently seen spectacular progress and it is now understood that the role of TF in angiogenesis is both
|
|
coagulation-dependent and independent. The recent evidence for this emerging insight will be the subject of
|
|
this review.
|
|
</p>
|
|
<p>
|
|
Semin Thromb Hemost. 2003 Jun;29(3):317-20. <strong>Occurrence of components of fibrinolytic pathways in
|
|
situ in laryngeal cancer.</strong>
|
|
Wojtukiewicz MZ, Sierko E, Zacharski LR, Rozanska-Kudelska M, Zimnoch L.
|
|
</p>
|
|
<p>
|
|
Semin Thromb Hemost. 2003 Jun;29(3):239-46. <strong>Malignancy as a solid-phase coagulopathy: implications
|
|
for the etiology, pathogenesis, and treatment of cancer.</strong> Zacharski LR.
|
|
</p>
|
|
|
|
<p>
|
|
Thromb Res. 2003 Jun 1;110(4):213-4. <strong>Heparin treatment of malignancy: the case for clinical trials
|
|
in colon cancer.</strong> Zacharski LR.
|
|
</p>
|
|
<p>
|
|
Anticancer Res. 2003 May-Jun;23(3C):2789-93. <strong>Low-molecular-weight heparin in oncology.</strong>
|
|
Zacharski LR, Loynes JT.
|
|
</p>
|
|
<p>
|
|
Cancer Lett. 2002 Dec 1;186(1):1-9. <strong>
|
|
Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy.</strong> Zacharski LR.
|
|
</p>
|
|
|
|
<p>© Ray Peat 2006. All Rights Reserved. www.RayPeat.com</p>
|
|
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