| ||Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP|
| ||The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigarin|
| ||Programmed cell death as a new target for prostatic cancer therapy|
| ||Hypercalcemia in carcinoma of the prostate: Case report and review of the literature|
| ||Calcium excretion in metastatic prostatic carcinoma|
| ||Chemoprevention of colorectal tumors: role of lactulose and of other agents.|
| ||[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]|
| ||Different effects of PTH on erythrocyte calcium influx|
| ||Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: Comparison with primary hyperparathyroidism|
| ||Osteoclast cytomorphometry in patients with femoral neck fracture|
| ||The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands|
| ||Role of parathyroid hormone-related peptide (PTHrP) in hypercalcemia of malignancy and the development of osteolytic metastases|
| ||Experimental study of glucocorticoid-induced rabbit osteoporosis|
| ||24,25 dihydroxyvitamin D supplementation corrects Intradialytic calcium balances with different calcium dialysate levels. Effects on cardiovascular stability and parathyroid function|
| ||Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients|
| ||Calcium, phosphate, vitamin D, and the parathyroid|
| ||The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density|
| ||Bone mineral density changes during lactation: Maternal, dietary, and biochemical correlates|
| ||Postprandial parathyroid hormone response to four calcium-rich foodstuffs|
| ||Complementary medical treatment for Colles' fracture: A comparative, randomized, longitudinal study|
| ||Treatment of postmenopausal osteoporosis: Spoilt for choice? Part 1 - Foundations for an individually adapted management concept|
| ||Calcium and vitamin D in the prevention and treatment of osteoporosis|
| ||Calcium intake and fracture risk: Results from the study of osteoporotic fractures|
| ||Bone loss and turnover after cardiac transplantation|
| ||What's hip in diet and osteoporosis?|
| ||A high dietary calcium intake is needed for a positive effect on bone density in Swedish postmenopausal women|
| ||Amelioration of hemiplegia-associated osteopenia more than 4 years after stroke by 1alpha-hydroxyvitamin D3 and calcium supplementation|
| ||The usefulness of bone turnover in predicting the response to transdermal estrogen therapy in postmenopausal osteoporosis|
| ||Osteoporotic vertebral fractures in postmenopausal women|
| ||Proteins and bone health|
| ||Osteoporosis: Prevention, diagnosis, and management|
| ||Connections between phospho-calcium metabolism and bone turnover. Epidemiologic study on osteoporosis (second part)|
| ||Calcium regulation and bone mass loss after total gastrectomy in pigs|
| ||Management of osteoporosis in the elderly|
| ||Effect of measuring bone mineral density on calcium intake|
| ||Osteoporosis: Its pediatric causes and prevention opportunities|
| ||Estimated dietary calcium intake and food sources for adolescent females: 1980-92|
| ||The pathogenesis of age-related osteoporotic fracture: Effects of dietary calcium deprivation|
| ||Osteoporosis prevention and treatment. Pharmacological management and treatment implications|
| ||Calcium metabolism in the elderly|
| ||Therapy of osteoporosis: Calcium, vitamin D, and exercise|
| ||Pathophysiology of osteoporosis|
| ||Risk for osteoporosis in black women|
| ||Age considerations in nutrient needs for bone health: Older adults|
| ||Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease|
| ||Harmonization of clinical practice guidelines for the prevention and treatment of osteoporosis and osteopenia in Europe: A difficult challenge|
| ||Clinical practice guidelines for the diagnosis and management of osteoporosis|
| ||Current and potential future drug treatments for osteoporosis|
| ||Calcium nutrition and osteoporosis|
| ||Osteoporosis of Crohn's disease: A critical review|
| ||The preparation and stability of compound active calcium tablets|
| ||Immunosuppression: Tightrope walk between iatrogenic side effects and therapy|
| ||Secondary osteoporosis in rheumatic diseases|
| ||Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women|
| ||Glucocorticoid-induced osteoporosis|
| ||Current treatment options for osteoporosis|
| ||Treatments for oestoporosis|
| ||Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: A preliminary report|
| ||The effect of calcium supplementation and Tanner Stage on bone density, content and area in teenage women|
| ||Osteoporosis and calcium ingest|
| ||Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: A 3 year followup|
| ||Novelties and issues in the drug market 1995|
| ||Influence of life style in the MEDOS study|
| ||Roles of diet and physical activity in the prevention of osteoporosis|
| ||The problem: Health impact of osteoporosis|
| ||Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: Comparative longitudinal study of bone mass|
| ||Nutritional prevention of aging osteoporosis|
| ||Osteoporotic fractures: Background and prevention strategies|
| ||Energy and nutrient intake in patients with CF|
| ||Current and future nonhormonal approaches to the treatment of osteoporosis|
| ||Transient osteoporosis of the hip. Case report and review of the literature|
| ||Osteomalacia and osteoporosis in a woman with ankylosing spondylitis|
| ||Calcium and vitamin D nutritional needs of elderly women|
| ||Heated oyster shell-seaweed calcium (AAA Ca) on osteoporosis|
| ||Calcium deficiency in fluoride-treated osteoporotic patients despite calcium supplementation|
| ||Axial bone mass in older women|
| ||Bone mineral density in mother-daughter pairs: Relations to lifetime exercise, lifetime milk consumption, and calcium supplements|
| ||Reduced bone mass in women with premenstrual syndrome|
| ||Calcium-regulating hormones across the menstrual cycle: Evidence of a secondary hyperparathyroidism in women with PMS|
| ||Calcium supplementation in premenstrual syndrome: A randomized crossover trial|
| ||Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). I.: Sunlight, dietary factors and epidemiology |
| ||Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women |
| ||Effect of glucocorticoids and calcium intake on bone density and bone, liver and plasma minerals in guinea pigs|
| ||Relationship between liver cirrhosis death rate and nutritional factors in 38 countries|
| ||Prophylaxis of recurring urinary stones: hard or soft mineral water|
| ||Prospective study of nutritional factors, blood pressure, and hypertension among US women.|
| ||Association of macronutrients and energy intake with hypertension.|
| ||Relations between magnesium, calcium, and plasma renin activity in black and white hypertensive patients|
| ||Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat.|
| ||Nonpharmacologic treatment of hypertension.|
| ||Micronutrient effects on blood pressure regulation.|
| ||Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-selective electrode.|
| ||Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).|
| ||Effect of dietary magnesium supplementation on intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats.|
| ||Impact of increasing calcium in the diet on nutrient consumption, plasma lipids, and lipoproteins in humans|
| ||Electrolytes and hypertension: results from recent studies.|
| ||Augmentation of the renal tubular dopaminergic activity by oral calcium supplementation in patients with essential hypertension.|
| ||The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.|
| ||Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure.|
| ||A prospective study of nutritional factors and hypertension among US men|
| ||Electrolytes in the epidemiology, pathophysiology, and treatment of hypertension.|
| ||Minerals and blood pressure.|
| ||The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension.|
| ||Dietary modulators of blood pressure in hypertension|
| ||Daily intake of macro and trace elements in the diet. 4. Sodium, potassium, calcium, and magnesium|
| ||Calcium intake: covariates and confounders|
| ||Nutrition and the elderly: a general overview.|
| ||Blood pressure and nutrient intake in the United States.|
| ||Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.|
| ||Endothelial function in deoxycorticosterone-NaCl hypertension: effect of calcium supplementation.|
| ||Prevention of preeclampsia with calcium supplementation and its relation with the L-arginine:nitric oxide pathway.|
| ||[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan]|
| ||Management of acute myocardial infarction in the elderly|
| ||Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables|
| ||The effects of calcium channel blockers on blood fluidity.|
| ||Concentrations of magnesium, calcium, potassium, and sodium in human heart muscle after acute myocardial infarction.|
| ||Nutrient intake and food use in an Ojibwa-Cree community in Northern Ontario assessed by 24h dietary recall|
| ||Mgsup 2sup +-Casup 2sup + interaction in contractility of vascular smooth muscle: Mgsup 2sup + versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels|
| ||Antacids drugs: Multiple but too often unknown pharmacological properties|
| ||Trace elements in prognosis of myocardial infarction and sudden coronary death|
| ||Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.|
| ||[Amyotrophic lateral sclerosis--causative role of trace elements]|
| ||Aluminum Deposition in Central Nervous System of Patients with Amyotrophic Lateral Sclerosis From the Kii Peninsula of Japan|
| ||[Deficiency of certain trace elements in children with hyperactivity]|
| ||Augmented Ca2+ in-flux is involved in the mechanism of enhanced proliferation of cultured vascular smooth muscle cells from spontaneously diabetic Goto-Kakizaki rats|
| ||The central role of calcium in the pathogenesis of cardiovascular disease|
| ||Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden|
| ||Natural products and their derivatives as cancer chemopreventive agents|
| ||New agents for cancer chemoprevention|
| ||Frequently nebulized beta-agonists for asthma: effects on serum electrolytes.|
| ||Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease.|
| ||Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism|
| ||Oral vitamin D or calcium carbonate in the prevention of renal bone disease?|
| ||Comparison of effects of calcitriol and calcium carbonate on secretion of interleukin-1beta and tumour necrosis factor-alpha by uraemic peripheral blood mononuclear cells|
| ||Effect of dietary calcium on urinary oxalate excretion after oxalate loads|
| ||The lack of influence of long-term potassium citrate and calcium citrate treatment in total body aluminum burden in patients with functioning kidneys|
Augmentation of the renal tubular dopaminergic activity by oral calcium supplementation in patients with essential hypertension.
Am J Hypertens (UNITED STATES) Nov 1993, 6 (11 Pt 1) p933-7
We studied the effect of oral calcium supplementation on renal tubular dopaminergic activity in patients with mild to moderate essential hypertension. Fifteen patients aged 45 to 68 years (nine men and six women, mean age 59 +/- 7 [SD]) participated in the study. We orally administered calcium (1.0 g per day for 1 week) during hospitalization. The change in 24-h blood pressure (BP), measured by ambulatory BP monitoring, and excretions of electrolytes and catecholamines were investigated before and after 1 week of oral calcium supplementation. The mean values of 24-h systolic and diastolic BP showed no significant changes by calcium loading. Daily urinary excretion of free dopamine, sodium clearance (CNa), fractional excretion of sodium (FENa), and urinary volume were significantly increased by oral calcium supplementation. Urinary excretions of epinephrine and norepinephrine and creatinine clearance showed no significant changes by oral calcium treatment. CNa and FENa showed significant correlations with urinary excretion of free dopamine. These results suggest that oral calcium supplementation induces natriuresis partly through augmentation of renal tubular dopaminergic activity.
The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.
Med Hypotheses (ENGLAND) Apr 1993, 40 (4) p250-6
'Magnesium ischaemia' is a term used to denote the functional impairment of the ATP-dependent sodium/potassium and calcium pumps in the cell membranes and within the cell itself. The production of ATP and the functioning of these pumps is magnesium-dependent and is critically sensitive to acidosis. Zinc and iron deficiencies may secondarily impair these pumps and thus contribute to 'magnesium ischaemia' (as does acidosis). This term is two-dimensional at its simplest; it refers to a functional magnesium deficiency, whether actual or induced. It is argued that chronic acidosis is the most common inducing factor. This simple hypothesis can begin to unify diverse pathophysiologies: some spontaneous abortions, aspects of Type II and gestational diabetes and the curious observation that heroin addicts become diabetic. It can also unify clinical thinking about pregnancy-induced hypertension, pre-eclampsia/eclampsia and acute fatty liver of pregnancy, as well as the coagulopathy of pregnancy. It makes important predictions about perinatal morbidity and suggests that early supplementation might prevent much pregnancy-induced disease.
Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure.
Clin Exp Hypertens [A] (UNITED STATES) 1992, 14 (6) p1189-209
Alterations in intracellular cation metabolism have been implicated in the pathophysiology of essential hypertension. Total magnesium, calcium, sodium and potassium levels were studied in serum erythrocytes and platelets, from 154 subjects (76 hypertensive and 78 normotensives; 104 blacks and 50 whites). In the combined black and white hypertensive group, platelet sodium and calcium and erythrocyte calcium were elevated and serum potassium, serum magnesium and platelet magnesium decreased. In the black hypertensive patients, platelet sodium and calcium and erythrocyte calcium were increased, whereas serum magnesium, serum potassium, platelet magnesium and erythrocyte magnesium were decreased. In the white hypertensive group, platelet sodium and erythrocyte calcium were raised and platelet magnesium was decreased. In the black hypertensive patients, serum and platelet magnesium and serum calcium were negatively and erythrocyte and platelet calcium positively correlated with mean arterial pressure. In the white hypertensive patients platelet sodium was directly related to mean arterial pressure. These results suggest that intracellular sodium and calcium overload and magnesium depletion may be important in the pathophysiology of hypertension. Magnesium disturbances are more consistent and widespread in black hypertensive patients than in white hypertensive patients.
A prospective study of nutritional factors and hypertension among US men
Circulation (UNITED STATES) Nov 1992, 86 (5) p1475-84
BACKGROUND. An effect of diet in determining blood pressure is suggested by epidemiological studies, but the role of specific nutrients is still unsettled. METHODS AND RESULTS. The relation of various nutritional factors with hypertension was examined prospectively among 30,681 predominantly white US male health professionals, 40-75 years old, without diagnosed hypertension. During 4 years of follow-up, 1,248 men reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary fiber, potassium, and magnesium were each significantly associated with lower risk of hypertension when considered individually and after adjustment for age, relative weight, alcohol consumption, and energy intake. When these nutrients were considered simultaneously, only dietary fiber had an independent inverse association with hypertension. For men with a fiber intake of < 12 g/day, the relative risk of hypertension was 1.57 (95% confidence interval, 1.20-2.05) compared with an intake of > 24 g/day. Calcium was significantly associated with lower risk of hypertension only in lean men. Dietary fiber, potassium, and magnesium were also inversely related to baseline systolic and diastolic blood pressure and to change in blood pressure during the follow-up among men who did not develop hypertension. Calcium was inversely associated with baseline blood pressure but not with change in blood pressure. No significant associations with hypertension were observed for sodium, total fat, or saturated, transunsaturated, and polyunsaturated fatty acids. Fruit fiber but not vegetable or cereal fiber was inversely associated with incidence of hypertension. CONCLUSIONS. These results support hypotheses that an increased intake of fiber and magnesium may contribute to the prevention of hypertension.
Electrolytes in the epidemiology, pathophysiology, and treatment of hypertension.
Prim Care (UNITED STATES) Sep 1991, 18 (3) p545-57
The data regarding the value of manipulating electrolytes in hypertension are controversial. It appears there are subsets of hypertensive patients who respond with lowering of blood pressure in conjunction with changes in intake of sodium, potassium, and calcium. The information regarding phosphorus and magnesium is less convincing. This paper examines current reports regarding these electrolytes and their role in the pathophysiology and treatment of essential hypertension. (52 Refs.)
Minerals and blood pressure.
Ann Med (FINLAND) Aug 1991, 23 (3) p299-305
The mineral elements sodium, potassium, calcium and magnesium play a central role in the normal regulation of blood pressure. In particular, these mineral elements have important interrelationships in the control of arterial resistance. These elements, especially sodium and potassium, also regulate the fluid balance of the body and, hence, influence the cardiac output. Evidence shows that the present levels of intake of mineral elements are not optimum for maintaining normal blood pressure but predispose to the development of arterial hypertension. Research results suggest that without sodium chloride (common salt) and other sodium compounds being added to the diet arterial hypertension would be virtually non existent. Moreover, blood pressure would not rise with age. In communities with a high consumption of added sodium, a high intake of potassium and, possibly, magnesium seem to protect against the development of arterial hypertension and the rise of blood pressure with age. A marked reduction of sodium intake is effective in treating even severe hypertension. A moderate restriction of sodium intake or an increase in potassium intake exert remarkable antihypertensive effects, at least in some hypertensive patients. Magnesium and possibly also calcium supplements may be effective in reducing blood pressure in some hypertensives. In hypertensive patients treated with drugs sodium restriction and potassium and magnesium supplementation enhance the therapeutic effect, reduce the number and dosage, and lessen the adverse effects of prescribed antihypertensive drugs. Hence, a fall in sodium consumption and increases in potassium and magnesium consumption are useful in preventing and treating arterial hypertension. (62 Refs.)
The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension.
Am J Hypertens (UNITED STATES) Jan 1991, 4 (1 Pt 1) p72-5
The effect of calcium and magnesium supplementation and the role of opioidergic system was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were divided into four groups receiving standard laboratory rat diet (control group; n = 9); a calcium-rich diet with 2% CaCl2 added (Ca-group; n = 12); a magnesium-rich diet with 0.5% MgO added (Mg-group; n = 11); and a calcium and magnesium-rich diet with 2% CaCl2 and 0.5% MgO added (Ca/Mg-group; n = 11); each diet contained 7% NaCl. After four weeks on these diets, the rats were decapitated and blood was obtained for the measurement of plasma electrolytes, intraerythrocyte sodium, potassium and magnesium content (RBC-Na, -K, in mEq/L cells and RBC-Mg, in mg/dL cells) and plasma beta-endorphin concentration (beta-END, in pg/mL). In the control group, systolic blood pressure and RBC-Na were obviously higher than in the other groups. Plasma beta-endorphin concentration was 45.1 +/- 13.4 in the control group, 70.7 +/- 17.4 in the Ca-group (P less than .05 v control group), 58.0 +/- 20.1 in the Mg-group and 83.8 +/- 24.8 in the Ca/Mg-group (P less than .01 v control group). The blood pressure correlated significantly with both RBC-Na (r = 0.416, P less than .01) and beta-END (r = 0.436, P less than .005). A negative correlation was also observed between RBC-Na and beta-END (r = 0.437, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary modulators of blood pressure in hypertension
Eur J Clin Nutr (ENGLAND) Apr 1990, 44 (4) p319-27
To study the role of diet, 197 patients of essential hypertension were randomized to either experimental diet (group A, 97 cases) or normal diet (group B, 100 cases) with diuretics given to both the groups. The age varied between 25 and 65 years and 154 were males. The study diet included a significantly higher content of potassium (K), magnesium (Mg), calcium (Ca), polyunsaturated fat, and complex carbohydrates compared to the normal diet. At entry to the study, age, sex, risk factors, mean blood pressures, mean serum Mg, K, Ca, and Na, and drug therapy were comparable in both groups. After 1 year of follow-up, there were significantly fewer patients with resistant hypertension in group A (5) than in group B (17). Mean systolic (148.22 +/- 10.1 mm Hg) and diastolic (90.2 +/- 4.84 mm Hg) pressures in group A were lowered compared to mean systolic (160 +/- 12.0 mm Hg) and diastolic (103.3 +/- 5.8 mm Hg) pressures in group B and initial mean systolic (152.2 +/- 12.8 mm Hg) and diastolic (99.8 +/- 7.2 mm Hg) pressures. Mean serum magnesium (1.86 +/- 9.22 mEq/l) and potassium (4.86 +/- 0.39 mEq/l) levels in group A were significantly higher compared to mean levels of 1.56 +/- 0.11 and 4.0 +/- 0.29 mEq/l, respectively, in group B. However compared to initial levels, K and Mg showed no significant changes in groups A and B. There was a significantly lower incidence of complications in group A (58) compared to group B (100). It is possible that a diet low in Na/K ratio and rich in complex carbohydrates, polyunsaturates, K and Mg may cause a significant reduction in blood pressure and its complications.
Daily intake of macro and trace elements in the diet. 4. Sodium, potassium, calcium, and magnesium
Ann Ig (ITALY) Sep-Oct 1989, 1 (5) p923-42
To complete the picture of the daily dietary intake of minerals, sodium, potassium, calcium and magnesium have now been considered. The study has been carried out in the Italian Marches Region after carefully evaluating the food consumption habits of the population. The foodstuffs comprising the 70 diets examined were collected in institutional canteens and private homes immediately prior to meals. The food was sampled ready for consumption as it had thus undergone the various preparation and cooking procedures, during which considerable changes in mineral content occur. In comparison with the various food consumption standards, the amount of sodium found appears excessively high (4.8 g/d) whereas that of magnesium is insufficient (0.24 g/d). A high sodium intake, and more recently a high Na/K ratio, have been associated with hypertension. Also a lack of magnesium and a high Ca/Mg ratio have repeatedly been associated with hypertension risk. The data to emerge from our study: a high sodium intake, an insufficiency of magnesium, and thus high Na/K and Ca/Mg ratios, would appear likely to enhance cardiovascular disease risk. Even though not all Authors agree on the existence of such correlations, a more correct diet as regards mineral intake is undoubtedly something to encourage.
Calcium intake: covariates and confounders
Am J Clin Nutr (UNITED STATES) Mar 1991, 53 (3) p741-4
One common nutrient postulated to be protective against osteoporosis, hypertension, and colon cancer is dietary calcium. We report here nutrient patterns by calcium intake in older adult residents of a geographically defined community in Southern California. The analysis included all 426 men and 531 women aged 50-79 y with complete 24-h diet data. Nutrient-density-adjusted calcium intake was divided into tertiles: low intake (less than 284 mg/1000 kcal), mid intake (284-440 mg/1000 kcal), and high intake (greater than 440 mg/1000 kcal). The distribution of the reported 24-h nutrient density of protein, fat, fiber, caffeine, trace minerals, vitamin D, and vitamin C was examined in relation to the calcium-intake tertiles. In both men and women, the adjusted intakes of protein, saturated fatty acids, vitamin D, magnesium, and phosphorus were significantly higher in the high-calcium-intake group than in the low- and mid-calcium-intake groups. In both men and women, alcohol intake was significantly lower in the high-calcium-intake group. Studies postulating a protective role for calcium will need to consider the multicolinearity in the Western diet.
Nutrition and the elderly: a general overview.
J Am Coll Nutr (UNITED STATES) 1984, 3 (4) p341-50
Throughout adult life, there is progressive alteration in body composition and tissue function. There is loss of lean body mass, notably by muscle, with a gain in body fat. We do not know whether nutritional factors affect these gross changes. In the case of loss of bone density (osteoporosis), however, there is evidence that the process is retarded by raising the intake of calcium and by exercise. Aging also adversely affects tissue function at the level of the whole organ and tissue as well as at the cellular and subcellular level. Animal models show similar age-related changes, and demonstrate further that alterations in nutrient intake or exercise can alter the rate of loss of tissue and cellular function. In addition to the effects of adult aging on tissue function, certain chronic diseases and disabilities are related to aging. These conditions include atherosclerosis, hypertension, coronary thrombosis, cancer, etc. Both human epidemiological studies and animal experiments on aging suggest strongly that nutrition plays a role in the onset and development of these conditions. There is a need for more accurate assessments of the nutrient needs of people over 65 years of age. A few selected nutrients are discussed. Studies of energy intake during adult life show a progressive reduction with increasing age, due mainly to reduced physical activity. Vitamin C levels in the white blood cells of elderly women can be half those of young adults; these respond to supplementary vitamin C without evidence of clinical benefit. Nitrogen balance studies suggest that the allowance of protein for older adults is not less than for young. Finally, surveys of elderly in whole populations and in selected groups show that, by the nutritional standards of young adults, there may exist a significant amount of malnutrition in people as they grow old, though we do not know whether this affects rate of loss of tissue function with age.
Blood pressure and nutrient intake in the United States.
Science (UNITED STATES) Jun 29 1984, 224 (4656) p1392-8
A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and vitamin C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.
Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.
Eur J Clin Nutr (ENGLAND) Jul 1996, 50 (7) p431-7
OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality. DESIGN: A nested case-control study within a prospective population study. SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.
Endothelial function in deoxycorticosterone-NaCl hypertension: effect of calcium supplementation.
Circulation (UNITED STATES) Mar 1 1996, 93 (5) p1000-8
BACKGROUND: Dietary calcium intake has been suggested to correlate inversely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances of the endothelium have not been well characterized. METHODS AND RESULTS: Wistar-Kyoto rats made hypertensive by deoxycorticosterone (DOC)-NaCl treatment, but a concurrent increase in chow calcium content from 1.1% to 2.5% markedly attenuated the rise in blood pressure. The function of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and ADP, as well as to nitroprusside, 3-morpholinosydnonimine, and isoproterenol were attenuated in hypertensive rats on 1.1% calcium supplementation. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rats and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ channels, and were further inhibited by blockade of ATP-dependent K+ channels with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-dependent hyperpolarization) were not impaired in hypertensive animals. The contractile sensitivity of endothelium-intact arterial rings to 5-hydroxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractile sensitivity caused by L-NAME corresponded in all groups. CONCLUSION: High-calcium diet markedly opposed experimental DOC-NaCl hypertension, an effect associated with improved arterial relaxation, while abnormalities of vascular contractile properties remained unaffected. In particular, the hyperpolarization-related component of endothelium-dependent arterial relaxation, mediated via opening of arterial K+ channels, could be augmented by calcium supplementation in DOC-NaCl hypertension.
Prevention of preeclampsia with calcium supplementation and its relation with the L-arginine:nitric oxide pathway.
Braz J Med Biol Res (BRAZIL) Jun 1996, 29 (6) p731-41
Pregnancy-induced hypertension (PIH) remains a common cause of maternal and fetal morbidity and mortality. During the past 7 years, some progress has been made in the prevention of PIH. Specifically, clinical studies have shown that supplementation with calcium can significantly reduce the frequency of PIH, especially in populations with a low calcium intake. We have suggested that, in such a population, calcium supplementation is a safe and effective measure for reducing the incidence of PIH. Calcium supplementation reduces the risk of PIH by maintaining the serum ionized calcium level which is crucial for the production of endothelial nitric oxide, the increased generation of which maintains the vasodilatation that is characteristic of normal pregnancy. In PIH there is an impaired nitric oxide synthesis and cyclic GMP production. (99 Refs.)
[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan]
Nippon Ronen Igakkai Zasshi (JAPAN) Dec 1996, 33 (12) p945-75
We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.
Management of acute myocardial infarction in the elderly
Drugs and Aging (New Zealand), 1996, 8/5 (358-377)
The prevalence of myocardial infarction (MI) is high among the elderly population. Many of the physiological and morphological changes attributable to 'normal' aging predispose older adults to cardiovascular instability. The incidence of both MIs and their associated morbidity and mortality increase with aging. Older MI patients may therefore derive substantial benefit from appropriately selected therapeutic intervention. In fact, given the high morbidity and mortality associated with MI in the elderly, aggressive therapeutic strategies may be particularly warranted. There are a number of age-related cardiovascular changes that contribute to the increasing incidence of MI as adults age. However, age itself is not a contraindication to aggressive therapy. Common MI management options include invasive and pharmaceutical strategies. The relative advantages of angioplasty and thrombolytics must be considered. Other drugs used in the treatment of MI include beta-blockers, ACE inhibitors, nitrates, aspirin, anticoagulants, magnesium, antiarrhythmics and calcium antagonists. Significant peri-infarction complications, including heart failure, hypotension, arrhythmias, myocardial rupture and cardiogenic shock, often occur in older adults. Age-specific management strategies for these complications are reviewed.
Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables
Heart and Lung: Journal of Acute and Critical Care (USA), 1996, 25/1 (31-36)
Objective: To explore the relationship between fluid and electrolyte variables and the development of supraventricular tachycardia (SVT) after coronary artery bypass grafting (CABG) surgery. Design: Retrospective chart review. Random selection from a list obtained from the medical records department and with use of the International Classification of Diseases code to identify patients undergoing their initial CABG. Setting: Medical records department of a southeastern 600-bed urban referral hospital with a large cardiovascular surgical program. Patients: Forty patients experiencing SVT and 40 patients not experiencing SVT during their stay in an intensive care unit after CABG. Outcome Measures: Fluid and electrolyte variables and the development of SVT in the intensive care unit after CABG. Variables: Data collected included preoperative demographic variables such as age and gender; previous history of SVT, congestive heart failure, cardiac arrest, previous surgery, diabetes, hypertension, valve disease, tobacco use, obesity; preoperative and postoperative medications; postoperative laboratory values of potassium, calcium, and magnesium; intravenous intake; hourly urine output; and chest tube drainage. Results: Demographic variables revealed that patients with SVT were older (p = 0.001) and had a higher incidence of preoperative SVT (p = 0.04). Although groups did not differ by numbers of patients with high or low potassium, calcium, or magnesium, patients receiving additional intravenous potassium by bolus after surgery had a higher incidence of SVT (p = 0.02). Patients who lost blood via the chest tube at a rate greater than 100 ml per hour for at least 1 hour after surgery had a higher incidence of SVT (p = 0.02). Patients with a urine output greater than 300 ml per hour for longer than 9 hours had an increased incidence of SVT (p = 0.02). In the patients experiencing SVT, 62% had it occur 24 to 48 hours after surgery. Conclusions: These data suggest that shifts in fluid and electrolytes may be important characteristics of patients in whom SVT will develop, which could lead to better identification and nursing management of SVT and improve hemodynamic status, patient recovery, and cost after CABG.
The effects of calcium channel blockers on blood fluidity.
J Cardiovasc Pharmacol (UNITED STATES) 1990, 16 Suppl 6 pS40-4
Although vasodilation, direct cardiac actions, or both represent the main properties of calcium channel blockers, there are further pharmacologic effects that may be therapeutically relevant. For example, hemorrheological effects, which have been demonstrated for a variety of calcium antagonists, have received relatively little attention to date. Hemorrheology describes the mechanics of blood and its components. It is of particular interest in the context of cardiovascular disease, as it has been shown that under certain conditions (reduced pump function, impaired vasomotor reserve), parameters of blood fluidity may be crucial for tissue perfusion. Whole-blood viscosity is the dominating factor in large arteries. For geometrical reasons, plasma viscosity and the rheological properties of blood cells may become of paramount importance at the microcirculatory level. In ischemic states, erythrocytes may be depleted of ATP, which they need for maintenance of normal shape and for transformation. This results in rigidification of the red blood cell and hindrance of its passage in the microcirculatory bed. Hence, blood flow deteriorates with the consequence of further unfavorable changes of the "milieu interieur," leading to the induction of a vicious cycle. Although effects on several hemorrheological parameters, for example, whole-blood viscosity, plasma viscosity, and red cell aggregation, can be demonstrated for various calcium channel blockers, the main rheological effects of these compounds are believed to consist in the improvement of erythrocyte deformability. When the ATP-dependent calcium pump is impaired in ischemia, calcium channel blockers may inhibit the slow inward transmembrane calcium flux and prevent the accumulation of intracellular calcium. (33 Refs.)
Concentrations of magnesium, calcium, potassium, and sodium in human heart muscle after acute myocardial infarction.
Clin Chem (UNITED STATES) Nov 1980, 26 (12) p1662-5
Atomic absorption spectrometry was used to measure magnesium, calcium, and sodium, and emission spectrometry to measure potassium, in myocardium (left and right ventricles) of 26 control subjects who died of acute trauma. Results were expressed in mumol/g of proteins. Mg/Ca and K/Na ratios were also determined. The same measurements were made in 24 patients who died from acute myocardial infarction. Samples were also taken from the necrotic area. Mg/Ca and K/Na ratios were significantly higher in the left ventricle of both populations, thus providing evidence of anatomical and physiological differences between the two ventricles. As a result of cytolysis and anoxia, the Mg/Ca ratio was very significantly inverted, and the K/Na ratio very significantly smaller, In these clinical conditions arrhythmias could certainly be considered likely, and there is reason to believe that magnesium depletion may be a cause of arrhythmias.
Nutrient intake and food use in an Ojibwa-Cree community in Northern Ontario assessed by 24h dietary recall
Nutrition Research (USA), 1997, 17/4 (603-618)
As part of a diabetes prevention program in a remote Ojibwa-Cree community in Northern Ontario, 72% of residents >9y of age (729/1019) underwent an oral glucose tolerance test; >98% (718/729) of participants provided a complete 24h dietary recall. Their diet was typical of that for aboriginal North American populations undergoing rapid cultural change, being high in saturated fat (similar13% energy), cholesterol and simple sugars (similar22% energy), low in dietary fibre (11g/d) and nigh in glycaemic index (similar90). There were high prevalences of inadequate intakes of vitamin A (77%), calcium (58%), vitamin C (40%) and folate (37%). Adolescents aged 10-19y consumed more simple sugars and less protein than adults aged >49y and ate more potato chips, flied potatoes, hamburger, pizza, soft drinks and table sugar. Adults >49y retained more traditional eating habits, using more bannock (fried bread) and wild meats than younger individuals. Interventions to prevent diabetes in the community should include culturally appropriate and effective ways to improve the nutritional adequacy of the diet, reduce fat intake and increase the use of less refined carbohydrate foods.
Mgsup 2sup +-Casup 2sup + interaction in contractility of vascular smooth muscle: Mgsup 2sup + versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels
CAN. J. PHYSIOL. PHARMACOL. (CANADA), 1987, 65/4 (729-745)
Contractility of all types of invertebrate muscle is dependent upon the actions and interactions of two divalent cations, viz., calcium (Casup 2sup +) and magnesium (Mgsup 2sup +)ions. The data presented and reviewed herein contrast the actions of several organic Casup 2sup + channel blockers with the natural, physiologic (inorganic) Casup 2sup + antagonist, Mgsup 2sup +, on microvascular and macrovascular smooth muscles. Both direct in vivo studies on microscopic arteriolar and venular smooth muscles and in vitro studies on different types of blood vessels are presented. It is clear from the studies done so far that of all Casup 2sup + antagonists examined, only Mgsup 2sup + has the capability to inhibit myogenic, basal, and hormonal-induced vascular tone in all types of vascular smooth muscle. Data obtained with verapamil, nimopidine, nitrendipine, and nisoldipine on the microvasculature are suggestive of the probability that a heterogeneity of Casup 2sup + channels, and of Casup 2sup + binding sites, exists in different microvascular smooth muscles; although some appear to be voltage operated and others, receptor operated, they are probably heterogeneous in composition from one vascular region to another. Mgsup 2sup + appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. The organic Casup 2sup + channel blockers do not have this uniform capability; they demonstrate selectivity when compared with Mgsup 2sup +. Mgsup 2sup + appears to be a special kind of Casup 2sup + channel antagonist in vasular smooth muscle. At vascular membranes it can (i) block Casup 2sup + entry and exit, (ii) lower peripheral and cerebral vascular resistance (iii) relieve cerebral, coronary, and peripheral vasospasm, and (iv) lower arterial blood pressure. At micromolar concentrations (i.e., 10-100 muM), Mgsup 2sup + can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mgsup 2sup + is three to five orders of magnitude less potent than the organic Casup 2sup + channel blockers, it possesses unique and potentially useful Casup 2sup + antagonistic properties.
Antacids drugs: Multiple but too often unknown pharmacological properties
Journal de Pharmacie Clinique (France), 1996, 15/1 (41-51)
This report considers recent procedures for evaluating the pharmacological properties of antacids, and the basis of their use in the treatment of gastroduodenal disorders. The described pharmacologic methods evaluate: (1) antacid capacity and antacid mechanisms in dynamic conditions by using 'the artificial stomach-duodenum' model, capable of simulating gastroduodenal flux regulation; (2) the pharmacological properties conferring a protective effect on the gastric mucosa, in vivo, by measuring (a) the reduction of pepsin activity, (b) the transepithelial potential difference, and (3) the molecular structure of adherent mucus glycoproteins and, in vitro, by assessing their ability to adsorb the duodenogastric reflux material. Three groups of antacids can be distinguished. (a) The aluminium-containing antacids which release aluminium in acid medium develop a potent buffering capacity, an action prolonged by their adsorption to the gastric mucosa. They induce a mucoprotective adaptation and adsorb the gastroduodenal reflux material. Their mechanism of H+ consumption is similar to that of proteins, which are natural antacids, i.e. H+ captation in acid medium and release of H+ ions which are normally neutralised by alkaline secretions in the duodenum. These long-acting antacids are indicated in the treatment of duodenal ulcer disease, in its prevention, and in that of gastritis. (b) Aluminium and magnesium hydroxide mixtures which form aluminium-magnesium combinations or magnesium and calcium associations mainly exert a neutralising activity with a strong pH rise, inducing rapid gastric emptying, and thereby reducing their activity duration. They do not exert protective effects on the gastric mucosa. They are indicated in the treatment of disorders related to hyperacidity or dyspeptic symptoms (gastrooesophageal reflux, pyrosis, slow gastric emptying, etc.). (c) Finally, alginic acid and alginate-containing antacids develop a pH gradient between acid contents and its surface, thus protecting the gastric and oesophageal mucosa; these preparations are indicated in the treatment of gastroesophageal reflux. Because these drugs are inexpensive and safe, they should be the first-time drugs of choice.
Trace elements in prognosis of myocardial infarction and sudden coronary death
Journal of Trace Elements in Experimental Medicine (USA), 1996, 9/2 (57-62)
Ca, Cu, Mg, Mn, and Zn concentrates were measured in plasma, RBC, and hair of 350 men aged 40-59 years with myocardial infarction (MI) and/or who died from sudden cardiac death (SCD), as compared with normal controls. Analyses were done by flame atomic absorption spectrophotometry. Cu in plasma of MI patients was significantly higher than the controls'. Plasma Mn was significantly lower in SCD than in MI subjects. No other consistent and significant changes were observed. Past and present evidence indicates that high plasma Cu levels may be associated with heart failure and rhythm disorders. The low plasma Mn levels may be an indicator of decreased parasympathetic tonus thus favouring myocardial desynchronization and A-V block. Cu inhibits phosphodiesterase activity and Mn inhibits andenylate cyclase activity thus exerting an influence on the contractility of cardiomyocites and of smooth muscle cells in coronary arteries. Cu and Mn analyses may thus have a prognostic significance for MI and SCD.
Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.
J Am Diet Assoc (UNITED STATES) May 1981, 78 (5) p477-82
Toxemia in pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In this study the dietary intakes of young pregnant women attending a Maternal and Infant Care Program at Tuskegee Institute were evaluated for selected vitamins and minerals. Women with toxemia were identified, and women without toxemia served as controls. The toxemia group generally consumed lesser amounts of vitamins and minerals than the controls. However, both groups were deficient (less than two-thirds RDA) in calcium, magnesium, vitamin B6, vitamin B12, and thiamin. Milk, meat, and grains supplied an appreciable proportion of each vitamin except vitamin A, which was found primarily in the two vegetable groups. Meat and grains contained the greatest quantities of minerals, but milk provided a relatively good proportion of potassium, calcium, magnesium, and phosphorus. Anemia was not related to the incidence of toxemia. Women exhibiting anemia consumed smaller amounts of vitamins studied than did women without anemia.
[Amyotrophic lateral sclerosis--causative role of trace elements]
Nippon Rinsho (JAPAN) Jan 1996, 54 (1) p123-8
Although numerous hypotheses have been proposed for the cause of amyotrophic lateral sclerosis (ALS), conclusive decision still remains vague. Recent epidemiological investigation disclosed an aggregation of ALS cases in the Western Pacific, including the Kii Peninsula of Japan, the island of Guam in Marianas and West New Guinea. Extensive environmental studies in these foci indicated an important role of trace elements in ALS etiology. It is postulated that chronic environment deficiencies of calcium and magnesium may provoke secondary hyperparathyroidism, resulting in increased intestinal absorption of toxic metals under the presence of excess levels of divalent or trivalent cations and lead to the mobilization of calcium and metals from the bone and deposition of these elements in nervous tissue. This hypothesis, called metal-induced calcifying degeneration of CNS, has been supported by experimental studies using several animal species. (15 Refs.)
Aluminum Deposition in Central Nervous System of Patients with Amyotrophic Lateral Sclerosis From the Kii Peninsula of Japan
Neurotoxicology, 1991; 615-620
Low calcium/magnesium intake with excess amounts of aluminum and manganese are associated with the incidence of amyotrophic lateral sclerosis (ALS) in the Western Pacific. Two Japanese case reports of ALS showed markedly elevated concentrations of aluminum in the CNS. In 6 other cases of ALS and 5 neurologically normal controls it was found that aluminum concentrations in the precentral gyrus, internal capsule, crus cerebri and spinal cord were significantly higher in 2 ALS patients compared to the controls. Mean aluminum concentrations in 26 different central nervous system regions in the 2 patients were higher than controls and 4 of the ALS cases. Magnesium concentrations in 26 central nervous system regions were markedly reduced in the ALS cases. Calcium/magnesium ratios were significantly increased in ALS patients. The authors conclude that the high incidence of ALS in the Western Pacific may be due to calcium/magnesium dismetabolism resulting in excess deposition of aluminum.
[Deficiency of certain trace elements in children with hyperactivity]
Psychiatr Pol (POLAND) May-Jun 1994, 28 (3) p345-53
The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group-healthy children from Szczecin. The highest deficit was noted in hair. Our results show that it is necessary to supplement trace elements in children with hyperactivity.
Augmented Ca2+ in-flux is involved in the mechanism of enhanced proliferation of cultured vascular smooth muscle cells from spontaneously diabetic Goto-Kakizaki rats
Atherosclerosis (Ireland), 1997, 131/2 (167-175)
To investigate whether augmented calcium influx is involved in the mechanism of the enhanced proliferation of vascular smooth muscle cells (VSMCs) in diabetes, we studied the association between proliferation and cytosolic free calcium concentration ((Ca2+)(i)) in cultured aortic VSMCs from spontaneously diabetic Goto-Kakizaki (GK) and Wistar rats. Serum, angiotensin II and Bay K 8644, a voltage-dependent Ca2+ channel (VDC) agonist, stimulated the proliferation of VSMCs; the magnitude was greater in VSMCs from GK than Wistar rats. VDC blockers, verapamil and nicardipine, inhibited Bay K 8644-induced cell proliferation, and the difference in the proliferation of VSMCs between GK and Wistar rats disappeared. Angiotensin II-induced proliferation was only partially inhibited by VDC blockers, and enhanced proliferation of GK-VSMCs was still observed. Bay K 8644 and angiotensin II increased (Ca2+)(i), and the increase was augmented in GK-VSMCs. Bay K 8644-induced (Ca2+)(i) increase was completely inhibited by pretreatment with verapamil or removal of extracellular Ca2+, suggesting that VDC is associated with this increase. Although angiotensin II-induced (Ca2+)(i) increase was not affected by verapamil, removal of extracellular Ca2+ slightly but significantly attotensin II-induced (Ca2+)(i) increase, suggesting that VDC blocker-insensitive receptor-activated Ca2+ influx is involved. These results indicate that augmented Ca2+ influx via VDC and a receptor-activated pathway may be involved in the mechanism of the enhanced proliferation of VSMCs from GK rats.
The central role of calcium in the pathogenesis of cardiovascular disease
Journal of Human Hypertension (United Kingdom), 1996, 10/3 (143-155)
Calcium-dependent processes play a central role in several different cells of the cardiovascular system including vascular smooth muscle and endothelial cells and also in monocytes, macrophages and platelets. In response to extracellular stimuli cytosolic calcium concentration increases. The increase is composed of two distinct phases. Firstly, calcium is released from intracellular stores via IP3. In the second phase calcium influx across the cell membrane is mostly responsible for the sustained rise in intracellular calcium concentration. This phase of the peak increase in cytosolic calcium is a prerequisite for sustained activation of the cell and the processes of vascular smooth muscle contraction and the activation of nuclear transcription factors for protein biosynthesis. Under ischemic conditions the regulatory systems which control the intracellular free calcium concentration consume a major portion of the cell's physiological energy supply (90%) and a decreased oxygen supply under ischemic conditions rapidly reduces the cell's capacity for intracellular calcium storage or outward transport across its membrane. Calcium antagonist drugs principally act on L-type calcium channels to reduce the influx of calcium into the the cells of the body. Since calcium antagonist drugs are able to influence a wide range of cellular processes which have been implicated in atherosclerosis, glomerulosclerosis, left ventricular hypertrophy and insulin resistance there are strong grounds for their use in a range of clinical disease states.
Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden
Cancer Epidemiology Biomarkers and Prevention (USA), 1996, 5/11(897-900)
The epidemiology of large bowel cancer suggests an etiological role for dietary factors. Although the evidence is inconsistent, several studies have suggested an inverse association between dietary vitamin D or calcium and colorectal cancer risk. We conducted a population-based case-control study to examine the relationship between dietary vitamin D and calcium and colorectal cancer among residents of Stockholm, Sweden. Between January 1986 and March 1988, 352 cases of colon cancer and 217 cases of rectal cancer diagnosed among living persons residing in Stockholm County were identified via a cancer surveillance network establisSweden and the Stockholm Regional Cancer Registry. Controls (512) were randomly selected from a computerized population registry. Dietary intake was assessed using a quantitative food frequency questionnaire focusing on average consumption during the preceding 5 years. Supplemental intake of vitamin D and calcium was not ascertained. Logistic regression was used to calculate odds ratios (ORs) as the measure of association between the exposure of interest (vitamin D or calcium) and cancer risk. Increasing levels of dietary vitamin D were inversely associated with the risk of colorectal cancer. The association was somewhat more pronounced for cancers of the rectum (OR, 0.5; 95% confidence interval (CI), 0.3-0.9 between the highest and lowest quartiles) than for cancers of the colon (OR, 0.6; 95% CI, 0.4-1.0) after adjustment for age, sex, and total caloric and protein intake. Dietary calcium was not associated with the adjusted risk of colon (OR, 1.2; 95% CI, 0.7-2.1) or rectal cancer (OR, 1.0; 95% CI, 0.5-1.9). Further adjustments for fat and dietary fiber intake, body mass index, and physical activity had little or no effect on the results. These results suggest that dietary vitamin D may reduce the risk of large bowel cancer, particularly rectal cancer. In addition, although some of the previous data suggested a protective effect for calcium against cancers of the large bowel, we could not document such an effect.
Natural products and their derivatives as cancer chemopreventive agents
Progress in Drug Research (Switzerland), 1997, 48/- (147-171) :
This review summarizes currently available data on the chemopreventive efficacies, proposed mechanisms of action and relationships between activities and structures of natural products like vitamin D, calcium, dehydroepidandrosterone, coenzyme Q10, celery seed oil, parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease inhibitors, tea polyphenols, curcumin, and polysaccharides from Acanthopanax genus.
New agents for cancer chemoprevention
Nation996, 63/SUPPL. 26 (1-28)
Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids (e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid), calcium, betacarotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylomithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3- carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs.Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being considered, such as vitamin E with l-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are ras isoprenylation and epidermal growth factor receptor inhibitors.
Frequently nebulized beta-agonists for asthma: effects on serum electrolytes.
Ann Emerg Med (UNITED STATES) Nov 1992, 21 (11) p1337-42
STUDY OBJECTIVE: To determine the magnitude of the changes in serum potassium, magnesium, and phosphate during the treatment of acute bronchospasm with repeated doses of beta-adrenergic agonists. DESIGN: Prospective study of a convenience sample of asthmatic patients. SETTING: University teaching hospital emergency department. TYPE OF PARTICIPANTS: Twenty-three patients met the inclusion criteria of age of more than 16 years; a history of asthma or chronic obstructive pulmonary disease; and an acute exacerbation. INTERVENTIONS: Baseline peak expiratory flow rate and serum potassium, magnesium, and phosphate levels were measured. Nebulized albuterol (2.5 mg) was administered every 30 minutes until the patient was discharged from the ED. Before each albuterol treatment, repeat serum levels of potassium, magnesium, and phosphate were determined. MEASUREMENTS AND MAIN RESULTS: Baseline peak expiratory flow rate averaged 188 +/- 119 L/min. Serum potassium levels decreased significantly (P = .0001 by repeated-measures analysis of variance) from 4.10 +/- 0.468 (baseline) to 3.55 +/- 0.580 mmol/L (90 minutes) and 3.45 +/- 0.683 mmol/L (180 minutes). Potassium decreased to less than 3.0 mmol/L in 22% of patients at some point during the study. Magnesium decreased from 1.64 +/- 0.133 mmol/L (baseline) to 1.48 +/- 0.184 mmol/L (90 minutes) and 1.40 +/- 0.219 mmol/L (180 minutes) (P = .0001). Phosphate levels also decreased, from 3.74 +/- 1.029 (baseline) to 2.84 +/- 0.957 mmol/L (90 minutes) and 2.55 +/- 0.715 mmol/L (180 minutes) (P = .0001). CONCLUSION: Aggressive administration of nebulized albuterol during the emergency treatment of acute bronchospasm is associated with statistically significant decreases in serum potassium, magnesium, and phosphate. The mechanism and clinical significance of these findings are unknown and warrant further study.
Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease.
Pharmacotherapy (UNITED STATES) Nov-Dec 1994, 14 (6) p729-33
STUDY OBJECTIVE. To evaluate the metabolic and cardiopulmonary effects of nebulized albuterol in patients suffering moderate to severe exacerbations of asthma or chronic obstructive pulmonary disease. DESIGN. Open-label, prospective study. SETTING. The emergency department of a university medical center. PATIENTS. Ten patients with moderate to severe exacerbation of asthma. INTERVENTIONS. Each patient received nebulized albuterol 2.5 mg for approximately 10 minutes. MEASUREMENTS AND MAIN RESULTS. Serum potassium, heart rate and rhythm, blood pressure, and pulmonary function were measured before treatment and every 15 minutes for 2 hours after treatment. Serum potassium concentrations decreased significantly (p < 0.05) within 75 minutes after initiation of treatment, from a baseline value of 4.5 +/- 0.6 mEq/L (range 3.5-5.5 mEq/L) to 3.7 +/- 0.5 mEq/L (range 2.8-4.4 mEq/L) at the end of the collection period (120 minutes). Forced expiratory volume in 1 second significantly increased over time in patients with asthma (p < 0.05). No statistically significant changes in blood pressure, heart rate, or corrected QT intervals occurred. Pre-emergency department use of a beta 2-agonist by metered-dose inhaler was not associated with a decreased serum potassium on admission. CONCLUSIONS. Nebulized beta 2-agonists are generally efficacious and safe in patients with acute bronchospasms. However, close monitoring of serum electrolytes, heart rate, and rhythm in patients at risk (elderly, those with pre-existing cardiac disease) is advised before these individuals receive repeat doses by continuous aerosol administration.
Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism
Mineral and Electrolyte Metabolism (Switzerland), 1996, 22/1-3 (196-199)
Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 plus or minus 0.1 (mean plus or minus SEM) to 1.9 plus or minus 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 plus or minus 0.1 to 2.47 plus or minus 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 plus or minus 0.02 (prestudy) to 1.28 plus or minus 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 plus or minus 5 to 8 plus or minus 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.
Oral vitamin D or calcium carbonate in the prevention of renal bone disease?
Current Opinion in Nephrology and Hypertension
It is well known that hyperparathyroidism begins early in renal failure and progresses, probably not linearly, throughout the natural course of renal diseases and dialysis therapy. Recent progress in basic medical science has improved our understanding of the mechanisms by which the classically known stimuli for parathyroid hormone synthesis and secretion may act, including hypocalcaemia, hyperphosphataemia and vitamin D3 metabolism disturbances. In the treatment of hyperparathyroidism, although some authors stress the benefit of treating one of these stimuli, it is probably more effective to combine the treatment of them all. There is conclusive recent work showing the efficacy of using both CaCO3 and vitamin D3, either in chronic renal failure or in dialsis patients at every stage of hyperparathyroidism. Therefore, the treatment of hyperparathyroidism should start early, long before dialysis, and it should aim to correct any of the causal factors. Both CaCO3 and vitamin D3 derivatives may be used in the prevention and treatment of renal bone disease. The limits of this association are the increasingly often reported adynamic bone disease, which in our experience has not yet given major clinical problems, and hyperphosphataemia. Uncontrolled serum phosphate levels would counterbalance the beneficial effect of vitamin D3 derivatives on hyperparathyroidism.
Comparison of effects of calcitriol and calcium carbonate on secretion of interleukin-1beta and tumour necrosis factor-alpha by uraemic peripheral blood mononuclear cells
Nephrology Dialysis Transplantation (United Kingdom), 1996, 11/SUPPL. 3 (15-21)
We studied 26 non-dialysed patients with chronic renal failure (creatinine clearance (CCr) 32.6 plus or minus 12.7 ml/min). They were divided into three groups according to their CCr and serum intact parathyroid hormone (PTH) and were given 0.5 microg/day oral calcitriol (calcitriol group, n = 8), 3 g/day calcium carbonate (CaCO3 group, n = 10), or neither (control uraemic group, n = 8). Serum intact PTH decreased from 154 plus or minus 75 to 90 plus or minus 43 pg/ml in the calcitriol group (P < 0.01) and from 162 plus or minus 97 to 77 plus or minus 62 pg/ml in the CaCO3 group (P < 0.001). Calcium carbonate was also effective in suppressing serum tartrate-resistant acid phosphatase, alkaline phosphatase and intact osteocalcin levels, while calcitriol did not suppress serum osteocalcin. Secretion of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) by phytohaemagglutinin A (PHA)-activated peripheral blood mononuclear cells (PBMC) was greater in uraemic patients than in age-matched healthy controls (n = 8). Calcitriol was effective in suppressing secretion of both cytokines, while calcium carbonate was capable of suppressing only TNF-alpha secretion. CCr decreased from 37.4 plus or minus 15.4 to 33.0 plus or minus 11.8 ml/min (P < 0.05) in the CaCO3 group, while it did not decrease in either the calcitriol group or the control uraemic group during a 6 month period. These results suggest that supplementation with calcitriol is necessary to maintain bone formation and normalize IL-1beta and TNF-alpha secretion by activated PBMC in uraemic patients.
Effect of dietary calcium on urinary oxalate excretion after oxalate loads
American Journal of Clinical Nutrition (USA), 1997, 65/5 (1453-1459)
An experimental model that allowed differentiation between endogenously and exogenously derived urinary oxalate was used to assess the effect of different forms and doses of ingested calcium on oxalate absorption and excretion. In replication 1 (R-1), subjects participated in three oxalate load (OL) tests: baseline (OL alone), calcium carbonate (OL with concomitant calcium carbonate ingestion), and calcium citrate malate (CCM) (OL with concomitant CCM ingestion). The calcium salts each provided 300 mg elemental Ca. OLs consisted of 180 mg unlabeled and 18 mg 1,2(13C2)oxalic acid. In R-2, subjects participated in four OL tests: baseline (OL alone) and OLs administered concomitantly with 100, 200, or 300 mg Ca. Timed urine samples after the OL were collected at 2-h intervals for the initial 6 h and samples were pooled into 9-h aliquots for the remaining 18 h of the 24 h period. In R-1, 24-h mean exogenous oxalate decreased (P < 0.05) after the OL from 36.2 mg (baseline) to 16.1 mg (after calcium carbonate) and to 14.3 mg (after CCM) whereas endogenous oxalate remained relatively constant. Mean 24-h oxalate absorption decreased significantly from that at the time of the baseline treatment (18.3%) after both calcium carbonate (8.1%) and CCM (7.2%) treatments. In R-2, mean 24-h oxalate absorption was significantly lower after 200 (5.9%) and 300 (7.6%) mg Ca than after 100 mg Ca (9.1%) and the OL alone (11.3%). Concomitant meal ingestion significantly decreased oxalate absorption in the absence of dietary calcium but not in association with the 300-mg Ca treatment. The overall data provide definitive evidence that dietary calcium can reduce oxalate absorption and excretion. Calcium carbonate and CCM were equally effective in this regard and a minimum of 200 mg elemental Ca maximized this effect in conjunction with an oxalic acid intake of 198 mg.
The lack of influence of long-term potassium citrate and calcium citrate treatment in total body aluminum burden in patients with functioning kidneys
Journal of the American College of Nutrition (USA), 1996, 15/1 (102-106)
Background: It has been suggested that citrate salts might enhance aluminum (Al) absorption from a normal diet, posing a threat of Al toxicity even in subjects with normal renal function. We have recently reported that in normal subjects and patients with moderate renal failure, short-term treatment with tricalcium dicitrate (Ca,Cit2) does not significantly change urinary and serum Al levels. However, we have not assessed total body Al stores in patients on long-term citrate treatment. Objective: The objective of this study was to ascertain body content of Al non-invasively using the increment in serum and urinary Al following the intravenous administration of deferoxamine (DFO) in patients with kidney stones and osteoporotic women undergoing long-term treatment with potassium citrate (K3Cit) or Ca3Cit2, respectively. Methods: Ten patients with calcium nephrolithiasis and five with osteoporosis who were maintained on potassium citrate (40 mEq/day or more) or calcium citrate 800 mg calcium/day (40 mEq citrate) for 2 to 8 years, respectively, and 1 h normal volunteers without a history of regular aluminum-containing antacid use participated in the study. All participants completed the 8 days of study, during which they were maintained on their regular home diet. Urinary Al excretion was measured during a two-day baseline before (Days 5, 6) and for 1 day (Day 7) immediately following a single intravenous dose of DFO (40 mg/kg). Blood for Al was obtained before DFO administration, and at 2, 5 and 24 hours following the start of the infusion. Results: The median 24-hour urinary Al excretion (microg/day) at baseline versus post-DFO value was 15.9 vs. 44.4 in the normal subjects and 13.3 vs. 35.7 in the patients. These values were all within normal limits and did not change significantly following DFO infusion (p = 0.003 and p = 0.0001, respectively). The median change of 17.1 microg/day in urinary Al in the normal subjects was not significantly different from the 18.7 microg/day change measured in the patient group (p 0.30). Similarly, no change in the mean serum Al was detected at any time following the DFO infusion, either in the patient or control group (patients 4.1 to 4.3 ng/ml, controls 7.4 to 4.6 ng/ml). Conclusion: The results suggest that abnormal total body retention of Al does not occur during long term citrate treatment in patients with functioning kidneys.