808 lines
67 KiB
HTML
808 lines
67 KiB
HTML
<html>
|
|
<head>
|
|
<title>Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy</title>
|
|
</head>
|
|
<body>
|
|
<h1>
|
|
Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy
|
|
</h1>
|
|
|
|
<p>
|
|
<em>
|
|
SOME CONTEXTS In biology and biochemistry, calcium is the substance most often studied, so it is
|
|
significant that researchers still speak of a calcium paradox. There are several such paradoxes: As
|
|
bones lose calcium, the soft tissues calcify; when less calcium is eaten, blood calcium may increase,
|
|
along with calcium in many organs and tissues; if an organ such as the heart is deprived of calcium for
|
|
a short time, its cells lose their ability to respond normally to calcium, and instead they take up a
|
|
large, toxic amount of calcium. Magnesium deficiency and calcium deficiency have some similar symptoms
|
|
(such as cramping), but magnesium is antagonistic to calcium in many systems. It is the basic protective
|
|
calcium blocker. Inflammation leads to excessive uptake of calcium by cells, and is a factor in obesity,
|
|
depression, and the degenerative diseases. Protein deficiency is an important cause of deranged calcium
|
|
metabolism. Vitamins K, E, and A are important in regulating calcium metabolism, and preventing
|
|
osteoporosis. Aspirin (with antiestrogenic and vitamin E-like actions) is protective against bone
|
|
resorption and hypercalcemia.
|
|
</em>
|
|
<hr />
|
|
It is extremely important to realize that calcium deposits in soft tissues become worse when the diet is <em
|
|
>low in calcium.</em> Persons suffering from arthritis, bursitis, scleroderma, hardening of the arteries and
|
|
any abnormality where calcium deposits or spurs may cause pain are often afraid to eat foods rich in
|
|
calcium. Actually they can never improve until their calcium and magnesium intakes are adequate. Not
|
|
infrequently physicians tell individuals with kidney stones to avoid all milk, thereby causing stones to
|
|
form even more rapidly. Such calcium deposits can also occur when vitamin E is undersupplied. After
|
|
open-heart surgery, when both magnesium and vitamin E are drastically needed and could easily be given, the
|
|
calcification of heart muscles often becomes so severe that it can cause death within a few days. Pages
|
|
171-172,<em>
|
|
Lets Eat Right to Keep Fit,</em> Adelle Davis, Signet, 1970.
|
|
|
|
<hr />
|
|
|
|
Almost all biologists think of the organism as a machine, regulated by information according to innate
|
|
programs. When it comes down to the details, their explanations sometimes make Rube Goldbergs imaginary
|
|
contraptions seem elegant. At their best, they usually rely on some mysterious things called ionic pumps,
|
|
that perform active transport, powered by little motors, under instructions from molecules that act on their
|
|
specific receptors. When things get unmanageable, the biologists speak of paradoxes. Calcium is the most
|
|
studied of all regulatory molecules, so it isnt surprising that there is more than one calcium paradox. But
|
|
there are ways of looking at the organism, focusing on energy metabolism, that dont involve the <em>ad
|
|
hoc</em> theory of calcium pumps, and that make it easy to keep things in context. Ionized atoms and
|
|
molecules behave in orderly ways, in relation to their size and their electrical charge. Organic material,
|
|
even when its dead, selectively binds certain metal ions, and excludes others. The living organism produces
|
|
a stream of metabolic products, such as carbon dioxide or lactic acid, which interact specifically with each
|
|
other and with the metal ions, modifying their concentrations inside cells and in the body fluids. This
|
|
movement of ions can be called active transport, without invoking the mysterious machinery of membrane
|
|
pumps. Chemical changes produced inside cells, for example by respiration, create different electrical
|
|
charges in different compartments (inside and outside of capillaries, for example) which affect the
|
|
movements of water and ions, by simple physical processes, not by molecular pumps. The result of these
|
|
passive and active processes is that each kind of ion has a characteristic concentration in each
|
|
compartment, according to the metabolic energy state of the organism. Magnesium and potassium are mainly
|
|
intracellular ions, sodium and calcium are mainly extracellular ions. When cells are excited, stressed, or
|
|
de-energized, they lose magnesium and potassium, and take up sodium and calcium. The mitochondria can bind a
|
|
certain amount of calcium during stress, but accumulating calcium can reach a point at which it inactivates
|
|
the mitochondria, forcing cells to increase their inefficient glycolytic energy production, producing an
|
|
excess of lactic acid. Abnormal calcification begins in the mitochondria. When cells are stressed or dying,
|
|
they take up calcium, which tends to excite the cells at the same time that it inhibits their energy
|
|
production, intensifying their stress. A cramp or a seizure is an example of uncontrolled cellular
|
|
excitation. Prolonged excitation and stress contribute to tissue inflammation and fibrosis. Gross
|
|
calcification generally follows the fibrosis that is produced by inflammation. Arteries, kidneys, and other
|
|
organs calcify during aging. At the age of 90, the amount of calcium in the elastic layer of an artery is
|
|
about 35 times greater than at the age of 20. Nearly every type of tissue, including the brain, is
|
|
susceptible to the inflammatory process that leads through fibrosis to calcification. The exception is the
|
|
skeleton, which loses its calcium as the soft tissues absorb calcium. These observations lead to some
|
|
simplifying ideas about the nature of aging and disease. Some people who know about the involvement of
|
|
calcium in aging, stress, and degeneration suggest eating a low calcium diet, but since we all have
|
|
skeletons, dietary calcium restriction cant protect our cells, and in fact, it usually intensifies the
|
|
process of calcification of the soft tissues. Statistics from several countries have clearly shown that the
|
|
mortality rate (especially from arteriosclerotic heart disease, but also from some other diseases, including
|
|
cancer) is lower than average in regions that have hard water, which often contains a very large amount of
|
|
either calcium or magnesium. Many studies have shown that dietary calcium (or vitamin D, which increases
|
|
calcium absorption) can have very important antiinflammatory effects. About 25 years ago, David McCarron
|
|
noticed that the governments data on diet and hypertension showed that the people who ate the most salt had
|
|
the lowest blood pressure, and those who ate the least salt had the highest pressure. He showed that a
|
|
calcium deficiency, rather than a sodium excess, was the most likely nutritional explanation for
|
|
hypertension. Hans Selye found that some steroids contribute to inflammation and calcification. Animals
|
|
could be sensitized to develop calciphylaxis, an intense, localized interaction of inflammation and
|
|
calcification. In the 1970s, Constance Martin pointed out that, up to that time, estrogen was known to
|
|
increase soft tissue calcium, but hadnt been shown to improve bone calcification and strength. Oxygen
|
|
deprivation, cyanide poisoning, x-irradiation, and all other sorts of injury also increase the calcium
|
|
content of soft tissues. One of Selyes colleagues, G. Jasmin, showed that magnesium deficiency causes
|
|
inflammation. A deficiency of either calcium or magnesium can stimulate the parathyroid glands to produce
|
|
more hormone (parathyroid hormone, PTH), which increases calcium absorption, but also removes calcium from
|
|
the bones. This hormone, responding to a dietary calcium or magnesium deficiency, is an important factor in
|
|
causing cells to take up too much calcium, and its excess is associated with many inflammatory and
|
|
degenerative diseases. Interleukin-6 (IL-6), an inflammatory cytokine which increases with aging, is
|
|
commonly considered to have an important role in the multiple processes of atrophy in old age. One of the
|
|
things which can increase the production of IL-6 is the parathyroid hormone (PTH), which increases the
|
|
amount of calcium circulating in the blood, partly by causing it to be removed from the bones; IL-6
|
|
stimulates the process of calcium removal from bones. Some of the interactions of hormones and other
|
|
regulatory chemicals are interesting, even though they are normally treated as if they were parts of a
|
|
machine that operates according to a hidden program written in the genes. Prolactin, which is increased
|
|
under the influence of estrogen or serotonin, causes the body to lose calcium (drawing it from the bones),
|
|
and it stimulates the secretion of PTH, which compensates for the calcium loss by increasing its
|
|
mobilization from bones. Prolactins action on bone is at least partly by increasing IL-6 formation; IL-6
|
|
stimulates the release of prolactin. Serotonin and IL-6 stimulate each others secretion, and PTH and
|
|
serotonin each stimulate the others release.. PTH (like estrogen and serotonin) inhibits cellular
|
|
respiration and activates glycolysis, lowering the ATP level and shifting the cells metabolism toward the
|
|
production of lactic acid rather than carbon dioxide. PTH also causes bicarbonate to be lost in the urine.
|
|
Since the formation of carbon dioxide lowers the intracellular pH, and the formation of lactic acid raises
|
|
it (through the reaction of NADH with pyruvate), the proteins in the cell become more strongly negatively
|
|
charged under the influence of oxygen deprivation, or under the influence of these hormones. In the cell
|
|
with high pH and increased negative electrical charge, the positively charged calcium ion is absorbed into
|
|
the cytoplasm. The calcium can enter from the relatively concentrated external fluid, but it can also be
|
|
released from acidic intracellular stores, the way serotonin is released by a disturbance of pH. There are
|
|
several other pro-inflammatory substances, such as the cytokines, that have a similar effect on cellular
|
|
energy systems. The antimetabolic actions of PTH mimic those seen in aging and diabetes, and surgical
|
|
removal of the parathyroid glands has been known to eliminate diabetes. PTH can cause diuresis, leading to
|
|
loss of blood volume and dehydration, hypertension, paralysis, increased rate of cell division, and growth
|
|
of cartilage, bone, and other tissues. Simply eating an adequate amount of calcium and magnesium can
|
|
alleviate many problems related to stress and aging that are considered serious, such as heart arrhythmia,
|
|
pancreatitis, and tissue calcification. The antiinflammatory, anti-allergy actions of calcium and magnesium
|
|
are well established, and there is clear evidence that obesity and various emotional disturbances can result
|
|
from their deficiency. Chronically high PTH can produce anemia, by a variety of mechanisms. Since a very low
|
|
sodium diet increases the loss of magnesium, by increasing aldosterone synthesis, simply increasing the
|
|
amount of sodium in the diet can help some people to balance their minerals and minimize stress. During
|
|
fasting and other intense stress, the kidneys destroy a large amount of protein to form ammonia to maintain
|
|
their ability to excrete acids, so using a large amount of the alkaline minerals can reduce the protein
|
|
catabolism. A diet of milk and fruit, or milk and meat, provides a nutritional balance with generous amounts
|
|
of calcium and magnesium. Leafy vegetables are a very rich source of magnesium, but they are also a
|
|
potential source of large amounts of lead and other toxins. In 1960, many people, including the
|
|
U.S.government, were advocating the use of a largely vegetarian diet for children, because of the amount of
|
|
radioactive strontium in milk. I compared the amount of strontium in a diet of vegetables that would provide
|
|
the necessary quantity of calcium and protein, and it was clear that vegetables were the worst source of
|
|
radioactive strontium, because their ratio of strontium to calcium was much higher than the ratio in milk.
|
|
The cows were concentrating calcium and protein from the contaminated plant foods, eliminating much of the
|
|
strontium. This principle still applies to the toxins that are currently found in the U.S. food supply. Milk
|
|
has many protective effects besides providing calcium. Many babies are being given milk substitutes (health
|
|
food drinks) made from soy or rice, with terrible consequences. The same products used by adults have less
|
|
disastrous effects in the short term, but are still likely to contribute to degeneration and dementia. Much
|
|
of the intracellular magnesium is complexed with ATP, and helps to stabilize that molecule. If cellular
|
|
energy production is low, as in hypothyroidism, cells tend to lose their magnesium very easily, shifting the
|
|
balance toward the lower energy molecule, ADP, with the release of phosphate. ADP complexes with calcium,
|
|
rather than magnesium, increasing the cells calcium content. Increased intracellular calcium, in association
|
|
with excess nitric oxide and excitatory amino acids, is involved in several neurodegenerative diseases,
|
|
including ALS, Alzheimers disease, Parkinsons disease, Huntingtons chorea, and epilepsy. Magnesium,
|
|
nicotine, progesterone, and many other substances are known to protect against excitotoxic calcium overload,
|
|
but there is no coherent effort in the health professions to make rational use of the available knowledge.
|
|
Respiration and carbon dioxide are the basic antagonists of the PTH. At birth, a baby has practically no
|
|
PTH, probably because of the high intrauterine concentration of carbon dioxide, but within a few days the
|
|
PTH rises. Increased carbon dioxide favors bone formation, and decreased bicarbonate favors the loss of
|
|
calcium from bone (Canzanello, et al., 1995; Bushinsky, et al, 2001). The use of sodium bicarbonate can
|
|
stimulate bone formation. A low protein diet, similar to that eaten by a large proportion of women (0.8 g/kg
|
|
of body weight) increases PTH, and so probably contributes to the development of osteoporosis and the
|
|
diseases of calcification. In an extreme protein deficiency, there is a shift towards inflammation,
|
|
serotonin excess, and excessive clotting, which might be related to the effect of the milder, more common
|
|
protein deficiency. Many people advocate a low protein diet, specifically to prevent or treat osteoporosis,
|
|
but the cultures that traditionally have had extremely high protein diets, such as the Masai, are very
|
|
healthy. Recent studies (see Bell and Whiting, 2002) are emphasizing the importance of animal protein in
|
|
preventing osteoporosis. Traditional meat-eating cultures efficiently use the whole animal, including blood,
|
|
skin, bones, and the various organs, rather than just the muscles. That diet is favorable for calcium
|
|
regulation, because it provides more vitamin A, D, E, and K, calcium, and gelatin, and less of the
|
|
pro-inflammatory amino acids, tryptophan and cysteine. Most loss of calcium from bones occurs during the
|
|
night. PTH tends to cycle with prolactin, which increases during the night, along with cortisol and the
|
|
other stress hormones. These nocturnal hormones probably account for the morning stiffness seen in many
|
|
rheumatic conditions, connective tissue diseases, and in aging. Progesterone, which increases the carbon
|
|
dioxide content of the tissues, is remarkably able to inhibit the actions of most of the inflammatory and
|
|
catabolic mediators, and to protect against degenerative calcification and osteoporosis. It also protects
|
|
against abnormal clotting. PTH increases platelet calcium concentration, and under some conditions can
|
|
produce inappropriate coagulation. Aspirin inhibits the actions of PTH, helping to prevent the calcification
|
|
of inflamed tissues, and it inhibits the loss of calcium from bones. Aspirin decreases the release of IL-6.
|
|
A protein called the PTH-related protein (PTHrP) has the same functions as PTH, but can be produced in any
|
|
tissue. It is responsible for the hypercalcemia of cancer, and is apparently involved in the frequent
|
|
metastasis of breast cancer to the bones. With only a small change in the theory of the nature of a living
|
|
organism, recognizing the importance of the interactions of metabolites and structural substances,
|
|
controlled by energetic metabolism, real progress could be made in understanding disease and health. The
|
|
most important calcium paradox is that medical journals (e.g.,
|
|
<em>International J. of Cardiology, </em>
|
|
Dec., 2002) are still promoting the idea that eating too much calcium causes hardening of the arteries and
|
|
other diseases of calcification.
|
|
|
|
<h3>REFERENCES</h3>
|
|
</p>
|
|
<p>
|
|
<strong>
|
|
J Am Soc Nephrol 1994 Apr;4(10):1814-9. A role of parathyroid hormone for the activation of cardiac
|
|
fibroblasts in Uremia.</strong> Amann K, Ritz E, Wiest G, Klaus G, Mall G. Thus, PTX abolished and PTH
|
|
restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role
|
|
of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.
|
|
</p>
|
|
<p>
|
|
Clin Endocrinol (Oxf) 1976 May;5(3):291-3. Recurrent hormone dependent chorea: effects of oestrogens and
|
|
progestogens. Barber PV, Arnold AG, Evans G.
|
|
</p>
|
|
<p>
|
|
Biochem Biophys Res Commun 2001 Feb 23;281(2):277-81. <strong>17 beta-estradiol increases Ca(2+) influx and
|
|
down regulates interleukin-2 receptor in mouse thymocytes.</strong> Azenabor AA, Hoffman-Goetz L.
|
|
</p>
|
|
|
|
<p>
|
|
Nutr Rev 2002 Oct;60(10 Pt 1):337-41. Elderly women need dietary protein to maintain bone mass. Bell J,
|
|
Whiting SJ. Researchers who conducted a recent prospective study of older adults reported that animal
|
|
protein had a protective role for bone, especially in elderly women, whereas plant protein was negatively
|
|
associated with bone mineral density. Other studies confirm the beneficial effect of increasing dietary
|
|
protein intake in older women to reduce bone mineral density loss and risk of fracture, suggesting that
|
|
emphasis should be placed on promoting adequate protein intake in elderly women.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Renal Physiol 2001 Dec;281(6):F1058-66. Metabolic, but not respiratory, acidosis increases bone
|
|
PGE(2) levels and calcium release. Bushinsky DA, Parker WR, Alexander KM, Krieger NS. A decrease in blood pH
|
|
may be due to either a reduction in bicarbonate concentration ([HCO(3)(-)]; metabolic acidosis) or to an
|
|
increase in PCO(2) (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases
|
|
urine calcium excretion without altering intestinal calcium absorption, indicating that the additional
|
|
urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis
|
|
increases net calcium efflux (J(Ca)), decreases osteoblastic collagen synthesis, and increases osteoclastic
|
|
bone resorption. Metabolic acidosis increases bone PGE(2) production, which is correlated with J(Ca), and
|
|
inhibition of PGE(2) production inhibits this acid-induced J(Ca). Thus metabolic, but not respiratory,
|
|
acidosis induces the release of bone PGE(2), which mediates J(Ca) from bone.
|
|
</p>
|
|
<p>
|
|
J Clin Endocrinol Metab 1991 Jan;72(1):69-76. Circadian variation in ionized calcium and intact parathyroid
|
|
hormone: evidence for sex differences in calcium homeostasis. Calvo MS, Eastell R, Offord KP, Bergstralh EJ,
|
|
Burritt MF. Serum intact PTH levels showed a significant circadian pattern in both sexes (P less than or
|
|
equal to 0.001).
|
|
</p>
|
|
<p>
|
|
J Lab Clin Med 1995 Jul;126(1):81-7. Effect of chronic respiratory acidosis on calcium metabolism in the
|
|
rat. Canzanello VJ, Kraut JA, Holick MF, Johns C, Liu CC, Madias NE. Chronic metabolic acidosis typically
|
|
results in hypercalciuria and negative calcium balance. The impact of chronic respiratory acidosis on
|
|
calcium metabolism has been less well studied. To address this issue, metabolic balance and static bone
|
|
histomorphometric data were obtained during a 14-day exposure of rats to 10% CO2 (blood pH 7.33, PaCO2 83 mm
|
|
Hg) and were compared with pair-fed controls. All rats were fed a 0.8% calcium diet. Urinary calcium
|
|
excretion (mg/period, mean +/- SEM) was increased during both week 1 and week 2 (16 +/- 3 vs 9 +/- 1 and 16
|
|
+/- 2 vs 9 +/- 1, CO2 group vs controls, respectively [p < 0.05]). Net intestinal calcium absorption
|
|
(intake minus fecal excretion) was increased throughout the period of hypercapnia (week 1, 213 +/- 19 mg vs
|
|
135 +/- 15 mg; week 2, 135 +/- 16 mg vs 43 +/- 14 mg; and cumulatively, 344 +/- 27 mg vs 178 +/- 20 mg, CO2
|
|
group vs controls [p < 0.01]). As a consequence of the marked increment in intestinal calcium absorption
|
|
during hypercapnia, mean net calcium balance was more positive than that of controls throughout the study
|
|
(week 1, 197 +/- 18 mg vs 126 +/- 15 mg; week 2, 120 +/- 15 mg vs 34 +/- 15 mg; and cumulatively, 317 +/- 25
|
|
mg vs 159 +/- 20 mg, CO2 group vs controls, respectively [p < 0.01]). There were no significant
|
|
differences in calcium intake, plasma total calcium, immunoreactive parathyroid hormone, 25-hydroxyvitamin
|
|
D, or creatinine clearance between the two groups.
|
|
</p>
|
|
|
|
<p>
|
|
Mov Disord 1991;6(4):355-7. An unusual cause of recurrent chorea. Caviness JN, Muenter MD. Lee Silverman
|
|
</p>
|
|
<p>
|
|
Bone 2000 Jan;26(1):79-85. <strong>
|
|
Correlation of estradiol, parathyroid hormone, interleukin-6, and soluble interleukin-6 receptor during
|
|
the normal menstrual cycle.</strong> Chiu KM, Arnaud CD, Ju J, Mayes D, Bacchetti P, Weitz S, Keller ET.
|
|
<strong><hr /></strong>
|
|
<hr />
|
|
<strong>These data demonstrate that IL-6 and PTH fluctuate with E2, and serum II-6 is associated with PTH
|
|
levels during the menstrual cycle.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
J Cell Sci 2002 Feb 1;115(Pt 3):599-607. pH-dependent regulation of lysosomal calcium in macrophages.
|
|
Christensen KA, Myers JT, Swanson JA. Average free calcium concentration in macrophage lysosomes was
|
|
4-6x10(-4) M, less than half of the extracellular calcium concentration, but much higher than cytosolic
|
|
calcium levels. pH-dependent reductions of lysosomal calcium concentrations appeared to result from calcium
|
|
movement out of lysosomes into cytoplasm, since increases in cytosolic calcium levels could be detected upon
|
|
lysosome alkalinization.
|
|
</p>
|
|
<p>
|
|
Adv Neurol 1979;26:123-33. Ovarian steroid hormones and cerebral function. Cogen PH, Zimmerman EA.
|
|
</p>
|
|
<p>
|
|
J Bone Miner Res 1996 Oct;11(10):1419-29. Stimulation of neonatal mouse calvarial bone resorption by the
|
|
glucocorticoids hydrocortisone and dexamethasone. Conaway HH, Grigorie D, Lerner UH. In vitro stimulation of
|
|
bone resorption was observed with the glucocorticoids hydrocortisone and dexamethasone. The 45Ca release
|
|
stimulated by 1 microM hydrocortisone and 0.1 microM dexamethasone was also inhibited by 10 microM
|
|
progesterone in a competitive manner and by 1 microM of the antiglucocorticoid RU38486, both of which are
|
|
modulators of glucocorticoid binding.
|
|
</p>
|
|
<p>
|
|
J Physiol 2002 Mar 15;539(Pt 3):791-803. MgATP counteracts intracellular proton inhibition of the
|
|
sodium-calcium exchanger in dialysed squid axons. DiPolo R, Beauge L. The increase in Ca(2+)(i) affinity
|
|
induced by ATP at acid pH (6.9) can be mimicked by a rise in pH(i) from 6.9 to 7.3 in the absence of the
|
|
nucleotide.
|
|
</p>
|
|
<p>
|
|
J Maine Med Assoc 1977 Oct;68(10):370-1 Quadriparesis as an unusual manifestation of hypercalcemia. Dyro FM.
|
|
</p>
|
|
<p><hr /></p>
|
|
|
|
<p>
|
|
Hypertension 1986 Jun;8(6):497-505. Effects of calcium infusion on blood pressure in hypertensive and
|
|
normotensive humans. Ellison DH, Shneidman R, Morris C, McCarron DA. Together, these data provide evidence
|
|
for interactions between dietary sodium intake and the cardiovascular response to calcium. They confirm that
|
|
hypertensive subjects exhibit enhanced parathyroid gland function even when dietary factors are controlled,
|
|
and they suggest that these subjects are more sensitive to the cardiovascular effects of short-term calcium
|
|
infusion.
|
|
</p>
|
|
<p>
|
|
Yale J Biol Med 1996 Sep-Dec;68(5-6):215-7. Diplopia associated with hyperparathyroidism: report of a case.
|
|
Forman BH, Ciardiello K, Landau SJ, Freedman JK. A patient with hypercalcemia due to primary
|
|
hyperparathyroidism presented with diplopia that resolved with surgical removal of his parathyroid adenoma
|
|
and normalization of his serum calcium values. No previous report of this feature of hyperparathyroidism has
|
|
been reported.
|
|
</p>
|
|
<p>
|
|
J Nutr Sci Vitaminol (Tokyo) 1985 Dec;31 Suppl:S15-9. <strong>Aging and calcium as an environmental
|
|
factor.</strong>
|
|
Fujita T Calcium deficiency is a constant menace to land-abiding animals, including mammals. Humans enjoying
|
|
exceptional longevity on earth are especially susceptible to calcium deficiency in old age. Low calcium and
|
|
vitamin D intake, short solar exposure, decreased intestinal absorption, and falling renal function with
|
|
insufficient 1,25(OH)2 vitamin D biosynthesis all contribute to calcium deficiency, secondary
|
|
hyperparathyroidism, bone loss and possibly calcium shift from the bone to soft tissue, and from the
|
|
extracellular to the intracellular compartment, blunting the sharp concentration gap between these
|
|
compartments. The consequences of calcium deficiency might thus include not only osteoporosis, but also
|
|
arteriosclerosis and hypertension due to the increase of calcium in the vascular wall, <strong>amyotrophic
|
|
lateral sclerosis and senile dementia due to calcium deposition
|
|
</strong>in the central nervous system, <strong>and a decrease in cellular function, because of blunting of
|
|
the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency
|
|
and others (Fig. 6)
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Ann N Y Acad Sci 1990;587:371-5. Cytokines and osteoporosis. Fujita T, Matsui T, Nakao Y, Shiozawa S, Imai
|
|
Y. Conditions associated with immune dysfunction such as aging, corticosteroid therapy, and rheumatoid
|
|
arthritis are associated with osteoporosis, which is also more common in females than in males, like most of
|
|
the autoimmune-collagen diseases. Peripheral lymphocyte subsets CD4/CD8 were higher in patients with senile
|
|
osteoporosis than in the age-matched controls, and returned to normal after 1 month of 1 alpha(OH)vitamin D3
|
|
treatment. Plasma interferon reflecting macrophage function decreased with advance in age and increased in
|
|
response to 1 alpha(OH)D3 treatment. As one of the immunoregulators, vitamin D tends to stimulate the
|
|
macrophage-natural killer system and suppress the lymphocyte system, stimulating TGF beta and TNF alpha
|
|
activity. Senile osteoporosis of low turnover thus appears to be associated with vitamin D deficiency, low
|
|
macrophage function, high CD4 lymphocyte proportion, low IL-1 and high IL-2 activity, low IFN alpha and high
|
|
IFN gamma activity, and low TGF beta and TNF alpha activity.
|
|
</p>
|
|
|
|
<p>
|
|
Contrib Nephrol 1991;90:206-11. <strong>
|
|
Calcium, parathyroids and aging.
|
|
</strong>
|
|
Fujita T Calcium is unique in its distribution in living organisms with an extremely high hard and soft
|
|
tissue and extra- intracellular concentration gradient. Calcium<strong>
|
|
deficiency through stimulating parathyroid hormone secretion tends to blunt such a difference by
|
|
paradoxically increasing the calcium concentration in the soft tissue and intracellular compartment.
|
|
Since aging is associated with the</strong> progressive aggravation of calcium deficiency, such blunting
|
|
also progresses with aging. The dysfunction, damage and death of cells occurring in all diseases<strong>
|
|
is always associated with a blunting of the extra- and intracellular calcium components. Calcium
|
|
supplement especially with highly biologically available active absorbable calcium, was associated with
|
|
the suppression of parathyroid</strong>
|
|
hormone secretion and the normalization of a such blunting <strong>of intercompartmental distribution of
|
|
calcium examples in hypertension and diabetes mellitus with evident improvement of clinical
|
|
manifestations and laboratory tests.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Presse Med 2001 Apr 7;30(13):653-8. [Hypovitaminosis D: a major worldwide public health problem]
|
|
Gannage-Yared MH, Tohme A, Halaby G. Mild to moderate hypovitaminosis D causes secondary hyperparathyroidism
|
|
increasing the risk of fracture, particularly femoral neck fracture. Vitamin D would also have an
|
|
antiinflammatory and anticancer effect. Hypovitaminosis D is frequently observed in Europe in the elderly,
|
|
particularly in the institutionalized population, but is also seen in otherwise healthy younger adults. An
|
|
estimated 40% of the young European population has some degree of hypovitaminosis D. Finally, the beneficial
|
|
effect of moderate sun exposure on cutaneous vitamin D synthesis (and psychological well-being) must not be
|
|
overlooked.
|
|
</p>
|
|
<p>
|
|
Mol Med 1996 Mar;2(2):204-10. <strong>
|
|
Parathyroid hormone-related protein is induced during lethal endotoxemia and contributes to
|
|
endotoxin-induced mortality in rodents.</strong> Funk JL, Moser AH, Strewler GJ, Feingold KR, Grunfeld
|
|
C. Parathyroid hormone-related protein (PTHrP) is a ubiquitous and highly conserved vasoactive peptide whose
|
|
role and regulation in normal physiology remain an enigma. Recently, we demonstrated that low-dose endotoxin
|
|
(LPS) induces intrasplenic, but not systemic, levels of PTHrP; and that tumor necrosis factor, a
|
|
pro-inflammatory cytokine, is the major mediator of this effect. We have therefore hypothesized that, with
|
|
higher, lethal doses of endotoxin, PTHrP could be induced in multiple tissues to such a degree that it could
|
|
contribute to the lethality of septic shock. In response to a near-lethal dose of endotoxin, PTHrP mRNA
|
|
levels increased acutely in every vital organ examined (spleen, lung, heart, kidney, and liver). Circulating
|
|
levels of PTHrP also increased, peaking 2 hr after administration of high-dose endotoxin. These<strong>
|
|
results suggest that PTHrP belongs to the cascade of pro-inflammatory cytokines induced during lethal
|
|
endotoxemia that is responsible for the toxic effects of</strong> LPS.
|
|
</p>
|
|
<p><hr /></p>
|
|
<p>
|
|
Calcif Tissue Int 1990 May;46(5):294-9. Effective therapy of glucocorticoid-induced osteoporosis with
|
|
medroxyprogesterone acetate. Grecu EO, Weinshelbaum A, Simmons R. The results lend support to the hypothesis
|
|
of a progesterone-glucocorticoid competitive antagonism at the bone level, though other possibilities can be
|
|
entertained, and suggest MPA as an effective therapy for glucocorticoid-induced osteoporosis in men.
|
|
</p>
|
|
|
|
<p>
|
|
Proc Soc Exp Biol Med 1986 Mar;181(3):438-42. <strong>Forskolin-induced bone resorption in neonatal mouse
|
|
calvaria in vitro.</strong> Gunasekaran S, Hall GE, Kenny AD <strong>Lactic acid release was increased
|
|
during the 96 hr of incubation in proportion to the calcium release in the media.</strong>
|
|
|
|
J Endocrinol 2000 Feb;164(2):129-38. <strong>Estrogen mediates the sex difference in post-burn
|
|
immunosuppression.</strong> Gregory MS, Duffner LA, Faunce DE, Kovacs EJ. Previous studies in our
|
|
laboratory have demonstrated that cell-mediated immune function was suppressed in female, but not male, mice
|
|
at 10 days after burn injury and was mediated,<strong>
|
|
in part, by increased production of interleukin-6 (IL-6).
|
|
</strong>
|
|
Increased circulating<strong>
|
|
concentrations of E(2) corresponded with suppressed delayed-type hypersensitivity (DTH) and
|
|
splenocyte-proliferative responses, and increased circulating concentrations of IL-6 in female mice
|
|
after burn. Ovariectomy
|
|
</strong>restored the suppressed DTH response and decreased IL-6 concentrations, and administration of
|
|
exogenous E(2) to both ovariectomized females and intact male mice resulted in a suppressed DTH response. In
|
|
addition, in vitro <strong>treatment with E(2) suppressed splenocyte proliferation in a macrophage-dependent
|
|
manner and enhanced macrophage production of IL-6.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Calcif Tissue Int 1990 May;46(5):294-9. Effective therapy of glucocorticoid-induced osteoporosis with
|
|
medroxyprogesterone acetate. Grecu EO, Weinshelbaum A, Simmons R.
|
|
</p>
|
|
<p>
|
|
Nephron 1982;30(3):237-9. Elevated thrombocyte calcium content in uremia and its correction by 1 alpha(OH)
|
|
vitamin D treatment. Gura V, Creter D, Levi J.
|
|
</p>
|
|
<p>
|
|
Fortschr Med 1985 Mar 28;103(12):328-30. <strong>
|
|
[Antiallergic effect of oral calcium.</strong> A clinico-experimental study] [Article in German] Haas
|
|
PJ. Randomized Controlled Trial
|
|
</p>
|
|
<p>
|
|
Acta Univ Carol Med Monogr 1972;53:427-32. The possible role of platelets as trigger in intravascular
|
|
coagulation associated with acute hyperparathyroidism. Hilgard P, Hohage R, Schmitt W, Minne H, Ziegler R.
|
|
</p>
|
|
|
|
<p>
|
|
Sci Total Environ 1986 Oct;54:207-16. Chemical qualities of water that contribute to human health in a
|
|
positive way. Hopps HC, Feder GL. The chemical substances in water that make positive contributions to human
|
|
health act mainly in two ways: (i) nutritionally, by supplying essential macro and micro elements that the
|
|
diet (excluding water) may not provide in adequate amounts (for example, Mg, I and Zn); and (ii) by
|
|
providing macro and micro elements that inhibit the absorbtion and/or effects of toxic elements such as Hg,
|
|
Pb and Cd. In this context, the inverse relationship between hard water and cardiovascular disease will be
|
|
discussed. Specific data relating hardness and Mg and Ca content of potable waters to specific geographic
|
|
regions of the U.S.A. will be presented. These data show a strong positive correlation between low Mg
|
|
content and decreased longevity, and between high Ca and Mg content and increased longevity. In the regions
|
|
considered, increased longevity correlates strongly with decreased cardiovascular mortality, and the
|
|
decreased longevity with increased cardiovascular mortality.
|
|
</p>
|
|
<p>
|
|
Calcif Tissue Res 1977 Oct 20;23(3):241-4.<strong>
|
|
Proliferation of osteoclasts in rat bone following bleeding and femoral fractures.</strong> Johnell O,
|
|
Hulth A This rise in the osteoclast population might be due to an increased parathyroid activity released by
|
|
the trauma, but other factors may be involved. Both bleedings and fractures in rats are followed by
|
|
hypercalcemia. Brain Behav Immun 2000 Mar;14(1):49-61. <strong>Modulation of IL-6 production during the
|
|
menstrual cycle in vivo and in vitro.</strong> Konecna L, Yan MS, Miller LE, Scholmerich J, Falk W,
|
|
Straub RH. Premenopausal female patients with chronic inflammatory diseases demonstrate changes in disease
|
|
activity during the MC. <strong><hr /></strong>
|
|
<hr />
|
|
|
|
Kidney Int Suppl 1983 Dec;16:S204-7. <strong>Pathogenesis of the anemia of uremia: role of secondary
|
|
hyperparathyroidism.</strong> Massry SG PTH may participate in the genesis of the anemia of uremia
|
|
through at least<strong>
|
|
three pathways. These include inhibition of erythropoiesis, shortening survival of RBCs and inducing
|
|
fibrosis of bone marrow cavity.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Braz J Med Biol Res 2002 Feb;35(2):229-36. Parathyroid hormone secretion in chronic human endogenous
|
|
hypercortisolism. Lanna CM, Paula FJ, Montenegro RM Jr, Moreira AC, Foss MC. Osteoporosis is a common
|
|
manifestation of Cushing's syndrome, but the mechanisms responsible for this abnormality have not been
|
|
defined. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to
|
|
controls.
|
|
</p>
|
|
<p>
|
|
Am J Clin Nutr 2000 Jul;72(1):168-73. <strong>
|
|
A threshold for low-protein-diet-induced elevations in parathyroid hormone.</strong>
|
|
|
|
Kerstetter JE, Svastisalee CM, Caseria DM, Mitnick ME, Insogna KL. <strong>
|
|
Elevations in PTH developed by day 4 of the diets containing 0.7 and 0.8 g protein/kg but not during the
|
|
diets containing 0.9 or 1.0 g protein/kg.</strong>
|
|
Our data suggest that in young healthy women consuming a well-balanced diet, the current recommended dietary
|
|
allowance for protein (0.8 g/kg) results in short-term perturbations in calcium homeostasis.
|
|
</p>
|
|
<p>
|
|
J Endocrinol 1995 Sep;146(3):421-9. Effect of oral calcium supplementation on intracellular calcium and
|
|
plasma renin in men. Lijnen P, Petrov V. Oral calcium supplementation in these men was also accompanied by a
|
|
reduction in the plasma concentration of intact parathyroid hormone and 1,25-dihydroxyvitamin D3, an
|
|
increase in 24-h urinary calcium excretion but no change in the plasma total Ca2+ concentration, serum
|
|
ionized Ca2+ level and plasma phosphate or 25-hydroxyvitamin D3.
|
|
</p>
|
|
<p>
|
|
Clin Sci (Lond) 1996 Sep;91(3):313-8. Effects of mineral composition of drinking water on risk for stone
|
|
formation and bone metabolism in idiopathic calcium nephrolithiasis. Marangella M, Vitale C, Petrarulo M,
|
|
Rovera L, Dutto F. The increase in overall calcium intake due to different drinking water induced modest
|
|
increases in calcium excretion, whereas oxalate excretion tended to decrease. The changes in oxalate
|
|
excretion during any one study period compared with another were significantly related to those in calcium
|
|
intake. Citrate excretion was significantly higher with the high-calcium, alkaline water. 4. Parathyroid
|
|
hormone, calcitriol and markers of bone resorption increased when patients were changed from the
|
|
high-calcium, alkaline to the low-calcium drinking water. 5. We suggest that overall calcium intake may be
|
|
tailored by supplying calcium in drinking water. Adverse effects on bone turnover with low-calcium diets can
|
|
be prevented by giving high-calcium, alkaline drinking water, and the stone-forming risk can be decreased as
|
|
effectively as with low-calcium drinking water.
|
|
</p>
|
|
<p>
|
|
J Endocrinol 1998 Feb;156(2):231-5. Calcium blood level modulates endogenous nitric oxide action: effects of
|
|
parathroidectomy in patients with hyperparathyroidism. Martina V, Bruno GA, Brancaleoni V, Zumpano E,
|
|
Tagliabue M, Fornengo R, Gasparri G, Pescarmona GP. In primary hyperparathyroidism (H-PTH) an increase in
|
|
platelet free calcium levels is present. After surgery, together with the normalization of calcium levels,
|
|
NO production also returned to normal values.
|
|
</p>
|
|
|
|
<p>
|
|
Hypertension 1980 Mar-Apr;2(2):162-8. Enhanced parathyroid function in essential hypertension: a homeostatic
|
|
response to a urinary calcium leak. McCarron DA, Pingree PA, Rubin RJ, Gaucher SM, Molitch M, Krutzik S.
|
|
Recent reports . . . suggest that increased parathyroid gland function may be one of the more common
|
|
endocrine disturbances associated with hypertension. Compared to a second age- and sex-matched normotensive
|
|
population, the hypertensives demonstrated a significant (p less than 0.005) relative hypercalciuria. For
|
|
any level of urinary sodium, hypertensives excreted more calcium. These preliminary data suggest that
|
|
parathyroid gland function may be enhanced in essential hypertension.
|
|
</p>
|
|
<p>
|
|
Am J Med 1987 Jan 26;82(1B):27-33. The calcium paradox of essential hypertension. McCarron DA, Morris CD,
|
|
Bukoski R. Three disparate observations--that calcium mediates vascular smooth muscle contraction, that
|
|
calcium channel blockers lower blood pressure, and that increased dietary calcium intake can also ameliorate
|
|
hypertension--constitute somewhat of a paradox. This evidence, and the paradoxical therapeutic efficacy of
|
|
both calcium channel blockers and supplemental dietary calcium, can be integrated into a single theoretic
|
|
construct.
|
|
</p>
|
|
<p>
|
|
Am J Hypertens 1995 Oct;8(10 Pt 1):957-64. Regulation of parathyroid hormone and vitamin D in essential
|
|
hypertension. Young EW, Morris CD, Holcomb S, McMillan G, McCarron DA. The maximal stimulated PTH level was
|
|
significantly higher in hypertensive than normotensive subjects in the absence of measured differences in
|
|
serum ionized calcium concentration, serum 1,25(OH)2-vitamin D concentration, and creatinine clearance.
|
|
</p>
|
|
<p>
|
|
J Clin Invest 1995 Apr;95(4):1933-40. <strong>
|
|
The diurnal rhythm of bone resorption in the rat. Effect of feeding habits and pharmacological
|
|
inhibitors.</strong> Muhlbauer RC, Fleisch H. This paper shows that, in rats, bone mass can be<strong>
|
|
increased by feeding habits per se. . . . we previously found a peak of bone resorption following food
|
|
administration. We now demonstrate that dividing the solid and liquid intake into portions blunts this
|
|
peak ....
|
|
</strong>
|
|
|
|
Whether bone mass in humans is also under the control of dietary habits is not known. <strong>If so, an
|
|
increased meal frequency may be used to prevent osteoporosis.
|
|
</strong>Nephron 2001 Dec;89(4):384-90. <strong>Prolonged dietary calcium restriction: a diagnostic approach
|
|
in idiopathic Hypercalciuria.</strong> Muller D, Eggert P.
|
|
</p>
|
|
<p><hr /></p>
|
|
|
|
<p>
|
|
J Appl Physiol 2001 Jun;90(6):2094-100. Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in
|
|
human pulmonary artery endothelial cells. Nishio K, Suzuki Y, Takeshita K, Aoki T, Kudo H, Sato N, Naoki K,
|
|
Miyao N, Ishii M, Yamaguchi K. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with
|
|
hypercapnic acidosis. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32
|
|
nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i
|
|
increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis.
|
|
Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it
|
|
markedly.
|
|
</p>
|
|
<p>
|
|
Clin Nephrol 2002 Mar;57(3):183-91.. Bone involvement in idiopathic hypercalciuria. Misael da Silva AM, dos
|
|
Reis LM, Pereira RC, Futata E, Branco-Martins CT, Noronha IL, Wajchemberg BL, Jorgetti V. A negative
|
|
correlation was observed between IL-6 levels and Z score of the femoral neck. Bone involvement was detected
|
|
in a young population with nephrolithiasis demonstrating that a strict follow-up is necessary in order to
|
|
control hypercalciuria.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Heart Circ Physiol 2002 Jul;283(1):H193-203. CaMKII-dependent reactivation of SR Ca(2+) uptake
|
|
and contractile recovery during intracellular acidosis. Nomura N, Satoh H, Terada H, Matsunaga M, Watanabe
|
|
H, Hayashi H. In hearts, intracellular acidosis disturbs contractile performance by decreasing myofibrillar
|
|
Ca(2+) response, but contraction recovers at prolonged acidosis.
|
|
</p>
|
|
<p>
|
|
J R Soc Health 1998 Apr;118(2):103-6. Lessons to be learned: a case study approach. Primary
|
|
hyperparathyroidism simulating an acute severe polyneuritis. Olukoga A. The case is presented of a 65 year
|
|
old lady with recent onset of neuromuscular manifestations, comprising paraparesis, areflexia and unsteady
|
|
gait, along with episodes of slurring of speech and diplopia, later confirmed to be due to severe
|
|
hypercalcaemia--which itself was caused by primary hyperparathyroidism.
|
|
</p>
|
|
|
|
<p>
|
|
Nippon Ronen Igakkai Zasshi 1989 May;26(3):216-22. <strong>[Calcium and magnesium metabolism in the
|
|
aged]</strong>
|
|
[Article in Japanese] Ouchi Y, Orimo H Although serum calcium concentration remains constant during ageing,
|
|
the plasma<strong>
|
|
concentration of calcium regulating hormones has been known to show dramatic change with ageing. The
|
|
plasma concentration of parathyroid hormone increases with ageing, whereas plasma concentrations of
|
|
calcitonin and active vitamin D metabolite decrease with ageing.</strong> On the other hand, the
|
|
incidence of <strong>soft tissue calcification is known to increase with ageing.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
J Clin Endocrinol Metab 1978 Sep;47(3):626-32. Calcium-regulating hormones during the menstrual cycle.
|
|
Pitkin RM, Reynolds WA, Williams GA, Hargis GK. In six subjects with cycle lengths of 27-31 days, PTH levels
|
|
rose progressively through the follicular phase to a peak at or slightly before the LH surge, then fell
|
|
progressively through the luteal phase; peak PTH levels were 30-35% above early follicular and late luteal
|
|
values. One subject experienced a prolonged (44 day) ovulatory cycle characterized by three distinct PTH
|
|
peaks, each of which coincided with elevations in plasma estradiol level.
|
|
</p>
|
|
<p>
|
|
Muscle Nerve 1982 Jan;5(1):26-32. <strong>
|
|
Hereditary polymyopathy and cardiomyopathy in the Syrian hamster. II. Development of heart necrotic
|
|
changes in relation to defective mitochondrial function.</strong> Proschek L, Jasmin G <strong>Since the
|
|
mitochondrial respiratory pattern and calcium overload parallel the cardiac degeneration, it is inferred
|
|
that the cell energy depletion is a functional consequence of an abnormal calcium influx.</strong>
|
|
|
|
Eur J Endocrinol 1998 Oct;139(4):433-7. <strong>Changes in cytochrome oxidase activity in brown adipose
|
|
tissue during oestrous cycle in the rat.</strong>
|
|
Puerta M, Rocha M, Gonzalez-Covaleda S, McBennett SM, Andrews JF. <strong>
|
|
The involvement of oestradiol in such a cycle is suggested by the fact that oestradiol treatment
|
|
decreased COX activity to values similar to those found in proestrus.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Am J Hypertens 1999 Dec;12(12 Pt 1-2):1217-24. Modification of intracellular calcium and plasma renin by
|
|
dietary calcium in men. Petrov V, Lijnen P. Our data show that the increase in PARA [plasma renin activity]
|
|
observed in men during oral calcium supplementation is accompanied by a reduction in the intracellular free
|
|
and total Ca2+ concentration in platelets and erythrocytes and by a decrease in the plasma concentration of
|
|
intact parathormone and 1,25-dihydroxyvitamin D3.
|
|
</p>
|
|
<p>
|
|
Arthritis Rheum 2001 Oct;44(10):2338-41. <strong>
|
|
Association of osteoporosis and cardiovascular disease in women with systemic lupus
|
|
erythematosus.</strong> Ramsey-Goldman R, Manzi S. These results demonstrate an association between
|
|
decreased BMD and both an increased carotid plaque index and presence of coronary artery calcification in a
|
|
small cohort of young women with lupus.
|
|
</p>
|
|
|
|
<p>
|
|
Am J Hypertens 1994 Dec;7(12):1052-7. Dietary calcium reduces blood pressure, parathyroid hormone, and
|
|
platelet cytosolic calcium responses in spontaneously hypertensive rats. Rao RM, Yan Y, Wu Y.
|
|
</p>
|
|
<p>
|
|
J Clin Endocrinol Metab 2002. May;87(5):2008-12 Potassium citrate prevents increased urine calcium excretion
|
|
and bone resorption induced by a high sodium chloride diet. Sellmeyer DE, Schloetter M, Sebastian A.
|
|
</p>
|
|
<p>
|
|
J Allergy Clin Immunol 1990 Dec;86(6 Pt 1):881-5 <strong>1,25-Dihydroxyvitamin D3 potentiates the decreased
|
|
response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine
|
|
monophosphate.</strong> Ravid A, Tamir R, Liberman UA, Rotem C, Pick AI, Novogrodsky A, Koren R. Eur J
|
|
Endocrinol 2002 May;146(5):635-42. <strong>Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin
|
|
D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and
|
|
phosphate metabolism.</strong> Rejnmark L, Lauridsen AL, Vestergaard P, Heickendorff L, Andreasen F,
|
|
Mosekilde L. <strong>With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major
|
|
hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations.
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Magnes Res 1999 Dec;12(4):257-67. Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone
|
|
formation and bone resorption. Rude RK, Kirchen ME, Gruber HE, Meyer MH, Luck JS, Crawford DL. Magnesium
|
|
(Mg) intake has been linked to bone mass and/or rate of bone loss in humans. Experimental Mg deficiency in
|
|
animal models has resulted in impaired bone growth, osteopenia, and increased skeletal fragility.
|
|
</p>
|
|
<p>
|
|
Schweiz Med Wochenschr 1994 Jun 25;124(25):1122-8. <strong>[Hypercalcemia]</strong> Schmid C. <strong>Severe
|
|
hypercalcemia is mainly caused by inappropriately high concentrations of compounds which promote bone
|
|
resorption, in particular PTH, PTHrP, or 1,25 (OH)2D3. The major consequences are impaired central
|
|
nervous system and kidney function (polyuria/dehydration);
|
|
</strong>
|
|
the latter, in turn, aggravate hypercalcemia via decreased fluid intake, mobility, and renal calcium
|
|
clearance.
|
|
</p>
|
|
<p>
|
|
J Neurophysiol 2002 May;87(5):2209-24. Intracellular pH response to anoxia in acutely dissociated adult rat
|
|
hippocampal CA1 neurons. Sheldon C, Church J. During perfusion with HCO/CO(2)- or HEPES-buffered media (pH
|
|
7.35) at 37 degrees C, 5- or 10-min anoxic insults were typified by an intracellular acidification on the
|
|
induction of anoxia, a subsequent rise in pH(i) in the continued absence of O(2), and a further internal
|
|
alkalinization on the return to normoxia. Reducing extracellular pH from 7.35 to 6.60, or reducing ambient
|
|
temperature from 37 degrees C to room temperature, also attenuated the increases in steady-state pH(i)
|
|
observed during and after anoxia and reduced rates of pH(i) recovery from acid loads imposed in the
|
|
immediate postanoxic period. The results suggest that a Zn(2+)-sensitive acid efflux mechanism, possibly a
|
|
H(+)-conductive pathway activated by membrane depolarization, contributes to the internal alkalinization
|
|
observed during anoxia in adult rat CA1 neurons. The rise in pH(i) after anoxia reflects acid extrusion via
|
|
the H(+)-conductive pathway and also Na(+)/H(+) exchange, activation of the latter being mediated, at least
|
|
in part, through a cAMP-dependent signaling pathway.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Heart Circ Physiol 2002 Dec;283(6):H2518-26. pH-induced changes in calcium: functional
|
|
consequences and mechanisms of action in guinea pig portal vein. Smith RD, Eisner DA, Wray S. The effects of
|
|
changing extracellular (pH(o)) and intracellular pH (pH(i)) on force and the mechanisms involved in the
|
|
guinea pig portal vein were investigated to better understand the control of tone in this vessel. When pH(o)
|
|
was altered, the effects on force and calcium were the same irrespective of whether force had been produced
|
|
spontaneously by high-K depolarization or by norepinephrine; alkalinization increased tone, and
|
|
acidification reduced it. Because pH(o) changes also lead to changes in pH(i), we determined whether the
|
|
effects on force could be explained by these induced pH(i) changes. It was found, however, that only with
|
|
spontaneous activity did intracellular alkalinization increase force. In depolarized preparations, force was
|
|
decreased, and, with norepinephrine, force was initially decreased and then increased. Thus the effects of
|
|
pH(o) cannot be explained solely by changes in pH(i). The role of the sarcoplasmic reticulum (SR) and
|
|
surface membrane Ca(2+)-ATPase on the mechanism were investigated and shown not to be involved. Therefore,
|
|
it is concluded that both pH(o) and pH(i) can have powerful modulatory effects on portal vein tone, that
|
|
these effects are not identical, and that they are likely to be due to effects of pH on ion channels rather
|
|
than the SR or plasma membrane Ca(2+)-ATPase.
|
|
</p>
|
|
|
|
<p>
|
|
Biochem Biophys Res Commun 2002 May 10;293(3):974-8. Arachidonic acid increases intracellular calcium in
|
|
erythrocytes. Soldati L, Lombardi C, Adamo D, Terranegra A, Bianchin C, Bianchi G, Vezzoli G.. Since
|
|
arachidonic acid and other polyunsaturated fatty acids influence the activities of most ion channels, we
|
|
studied their effects on the erythrocyte Ca(2+) influx. AA (5-50 microM) and EPA (20-30 microM) stimulated a
|
|
concentration-dependent increase in [Ca(2+)](i), deriving from extracellular calcium (1 mM), without
|
|
affecting the intra- and extracellular pH and membrane voltage. We conclude that AA could activate an
|
|
erythrocyte voltage-independent Ca(2+) transport via an intermediate product of cyclooxygenase pathway...
|
|
</p>
|
|
<p>
|
|
BMJ 1991 Mar 30;302(6779):762. Hormone replacement therapy induced chorea. Steiger MJ, Quinn NP. University
|
|
Department of Clinical Neurology, Institute of Neurology, London.
|
|
</p>
|
|
<p>
|
|
Nippon Naibunpi Gakkai Zasshi 1991 Dec 20;67(12):1319-38. [Cation metabolism and the effects of circulating
|
|
factors in pregnancy induced hypertension] Takashima M, Morikawa H, Yamasaki M, Mochizuki M. These data
|
|
suggest that the increase of p-[Ca2+]i and r-[Na+]i in PIH is important in the initiation and maintenance of
|
|
hypertension by influencing peripheral vascular resistance, and also various factors in the serum of PIH
|
|
women may contribute to the accumulation of intracellular ionized calcium in patients with PIH.
|
|
</p>
|
|
<p>
|
|
Hear Res 2001 Apr;154(1-2):81-7. Effects of gentamicin and pH on [Ca2+]i in apical and basal outer hair
|
|
cells from guinea pigs. Tan CT, Lee SY, Yao CJ, Liu SH, Lin-Shiau SY. By means of fura-2
|
|
microspectrofluorimetry, we measured the intracellular calcium concentration ([Ca2+]i) of OHCs bathed in
|
|
Hanks' balanced salt solution (pH 7.40) during either a resting state or high K+-induced depolarization.
|
|
While gentamicin and extracellular acidification (pH 7.14) can separately attenuate this increase in [Ca2+]i
|
|
in both types of OHCs, their suppressive effects are additive in basal OHCs, but not in apical OHCs.
|
|
</p>
|
|
|
|
<p>
|
|
Biochem Pharmacol 1983 Jan 15;32(2):355-60. Induction of mast cell secretion by parathormone. Tsakalos ND,
|
|
Theoharides TC, Kops SK, Askenase PW. The biologically active fragment of human parathormone (PTH) and
|
|
intact bovine PTH were found to induce secretion of both serotonin and histamine from rat peritoneal mast
|
|
cells in vitro. Intradermal injection of PTH induced immediate increases in vascular permeability suggesting
|
|
that PTH could induce mast cell secretion in vivo. These results demonstrate that elevated levels of PTH can
|
|
induce mast cell secretion in vitro and in vivo and suggest a possible role for mast cells in the
|
|
pathophysiology of non-allergic disease states.
|
|
</p>
|
|
<p>
|
|
J Neurol Sci 1989 Feb;89(2-3):189-97. Hyperestrogenemia in neuromuscular diseases. Usuki F, Nakazato O,
|
|
Osame M, Igata A. The cases, comprising bulbospinal muscular disease of the Kennedy-Alter-Sung type,
|
|
Kugelberg-Welander disease, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy, were all
|
|
euthyroid males. The baseline levels of serum estrone were significantly higher in all of the patients than
|
|
in age-matched normal subjects. Serum baseline testosterone, LH and FSH levels were all essentially normal,
|
|
except low FSH levels in Duchenne muscular dystrophy.
|
|
</p>
|
|
<p>
|
|
MMW Munch Med Wochenschr 1976 Oct 22;118(43):1395-8. <strong>[Oral application of calcium and vitamin D2 in
|
|
allergic bronchial asthma</strong>] Utz G, Hauck AM. Within 60 minutes after application, a
|
|
statistically significant reduction of airway resistance (Rt) and intrathoracic gas volume (IGV), as well as
|
|
an increase of forced exspiratory one second volume (FEV1) and forced inspiratory one second volume (FIV1)
|
|
was observed, in comparison with placebo. <strong>It is concluded that calcium, given orally in combination
|
|
with calciferol, causes a decrease of airway obstruction in patients with allergic bronchial asthma.
|
|
</strong>J Urol 1994 Oct;152(4):1226-8. <strong>Urinary incontinence due to idiopathic hypercalciuria in
|
|
children.
|
|
</strong>Vachvanichsanong P, Malagon M, Moore ES. In addition to being the most common cause of
|
|
microhematuria in children, our study demonstrates that idiopathic<strong>
|
|
hypercalciuria is also frequently associated with urinary incontinence of all types.
|
|
</strong>Magnes Trace Elem 1991-92;10(2-4):281-6. <strong>Relation of magnesium to osteoporosis and calcium
|
|
urolithiasis.</strong> Wallach S Magnesium influences mineral metabolism in hard and soft tissues
|
|
indirectly through hormonal and other modulating factors, and by direct effects on the processes of bone
|
|
formation and resorption and of crystallization (mineralization). Its causative and therapeutic
|
|
relationships to calcium urolithiasis (CaUr) are controversial despite an association between low urinary Mg
|
|
and CaUr. Recent studies have also found a tendency to low serum and/or lymphocyte Mg levels in CaUr.
|
|
Despite earlier studies demonstrating an inhibitory effect of Mg supplementation on experimental CaUr in
|
|
animals and in spontaneous CaUr in humans, at least two properly controlled clinical trials of Mg
|
|
supplementation have failed to demonstrate a beneficial effect on CaUr frequency. With regard to the
|
|
skeleton, experimental studies have shown that Mg depletion causes a decrease in both osteoblast and
|
|
osteoclast activity with the development of a form of 'aplastic bone disease'. At the same time, bone salt
|
|
crystallization is enhanced by Mg deficiency. Conversely, Mg excess impairs mineralization with the
|
|
development of an osteomalacia-like picture, and may also stimulate bone resorption independently of
|
|
parathyroid hormone. Whether or not Mg depletion may be a causal factor in human osteoporosis is also
|
|
controversial, and there are conflicting reports as to the Mg content of osteoporotic bone. Small decreases
|
|
in serum and/or erythrocyte Mg in osteoporotic patients have been reported, and one author has noted
|
|
improved bone mineral density with a multinutrient supplement rich in Mg. The extant data are sparse and
|
|
indicate a clear need for more rigorous study.
|
|
</p>
|
|
<p>
|
|
Semin Dial 2002 May-Jun;15(3):172-86 Calciphylaxis: emerging concepts in prevention, diagnosis, and
|
|
treatment. Wilmer WA, Magro CM. Several recent reports demonstrate that prolonged hyperphosphatemia and/or
|
|
elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the
|
|
likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or
|
|
protein S deficiency.
|
|
</p>
|
|
<p>
|
|
J Clin Lab Anal 1998;12(3):145-9. A proposal for standardizing urine collections for bone resorption markers
|
|
measurement. Zaninotto M, Bernardi D, Ujka F, Bonato P, Plebani M. The findings suggest that nocturnal
|
|
collection and first morning void samples provide the most reliable data on the rate of bone degradation,
|
|
possibly showing bone loss not only in osteopenic patients but also in women with a low T-score.
|
|
</p>
|
|
|
|
<p>
|
|
Am J Physiol Renal Physiol 2001 Aug;281(2):F366-73. Increased CO(2) stimulates K/Rb reabsorption mediated by
|
|
H-K-ATPase in CCD of potassium-restricted rabbit. Zhou X, Nakamura S, Xia SL, Wingo CS.
|
|
</p>
|
|
<p>
|
|
Sci Total Environ 1981 Apr;18:35-45 Water hardness and mortality in the Netherlands. Zielhuis RL, Haring BJ.
|
|
The hypothesis that the Ca and Mg deficiency in areas with soft drinking water increases the risk of I.H.D.
|
|
death rate was supported by the finding that food loses more Ca and Mg when it is cooked in soft water as
|
|
compared to cooking in hard water. However, investigation of a group of 17 municipalities of which mortality
|
|
and water quality data are known for three periods, 1958-1962, 1965-1970 and 1971-1977, showed that the
|
|
inverse statistical relation between I.H.D. Mortality and water hardness still existed but with decreasing
|
|
significance of correlation coefficients.
|
|
</p>
|
|
<p>
|
|
J Clin Endocrinol Metab 1980 Dec;51(6):1274-8. Serotonin stimulates adenosine 3',5'-monophosphate
|
|
accumulation in parathyroid adenoma. Zimmerman D, Abboud HE, George LE, Edis AJ, Dousa TP. Since cAMP acts
|
|
as a mediator of parathyroid hormone (PTH) release, our results suggest that serotonin could be one of the
|
|
factors regulating PTH secretion and/or contributing to PTH hypersecretion in various forms of primary
|
|
hyperparathyroidism.
|
|
</p>
|
|
<p>
|
|
Cas Lek Cesk 1997 Jul 30;136(15):459-63. <strong>
|
|
[New drugs with positive effects on bones]
|
|
</strong>
|
|
|
|
[Article in Czech] Zofkova I, Kanceva RL. Magnesium influences bone in different ways. <strong>It activates
|
|
osteoblasts, increases bone mineralization, and enhances the sensitivity of target tissues (incl. bone)
|
|
to PTH and 1,25(OH)2 vitamin D3,</strong> Under certain conditions however, magnesium can stimulate bone
|
|
resorption. A more potent factor than magnesium is stroncium, which not only activates osteoblats but
|
|
decreases the number of osteoclasts, thus abolishing bone resorption and enhancing formation. <strong>
|
|
Bicarbonates are also favourable for bone. NaHCO3 together with potassium citrate stimulates osteoblasts
|
|
and enhances bone mineralisation.</strong>
|
|
|
|
© Ray Peat Ph.D. 2009. All Rights Reserved. www.RayPeat.com
|
|
</p>
|
|
</body>
|
|
</html>
|