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MAGNESIUM



Table of Contents
image Magnesium and carbohydrate metabolism
image Disorders of magnesium metabolism
image Magnesium deficiency produces insulin resistance and increased thromboxane synthesis
image Magnesium and glucose homeostasis
image Magnesium content of erythrocytes in patients with vasospastic angina
image Variant angina due to deficiency of intracellular magnesium
image Magnesium and sudden death
image Magnesium deficiency produces spasms of coronary arteries: Relationship to etiology of sudden death ischemic heart disease
image Magnesium and potassium in diabetes and carbohydrate metabolism. Review of the present status and recent results.
image Hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate
image [Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]
image Magnesium hormonal regulation and metabolic interrelations
image Magnesium deficiency: Possible role in osteoporosis associated with gluten-sensitive enteropathy
image Energy and nutrient intake in patients with CF
image Kidney stone clinic: Ten years of experience
image Plasma copper, zinc and magnesium levels in patients with premenstrual tension syndrome
image Oral magnesium successfully relieves premenstrual mood changes
image Magnesium and the premenstrual syndrome
image Magnesium concentration in brains from multiple sclerosis patients
image Zinc, copper and magnesium concentration in serum and CSF of patients with neurological disorders
image The susceptibility of the centrocecal scotoma to electrolytes, especially in multiple sclerosis
image Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis.
image Magnesium concentration in plasma and erythrocytes in MS
image Comparative findings on serum IMg2+ of normal and diseased human subjects with the NOVA and KONE ISE's for Mg2+
image Migraine--diagnosis, differential diagnosis and therapy]
image Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study.
image Electromyographical ischemic test and intracellular and extracellular magnesium concentration in migraine and tension-type headache patients.
image Magnesium supplementation and osteoporosis
image Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women
image Magnesium in the physiopathology and treatment of renal calcium stones
image Urinary factors of kidney stone formation in patients with Crohn's disease
image Renal stone formation in patients with inflammatory bowel disease
image Magnesium metabolism in health and disease
image Prophylaxis of recurring urinary stones: hard or soft mineral water
image Urothelial injury to the rabbit bladder from various alkaline and acidic solutions used to dissolve kidney stones
image Cellular and humoral immunity in rats after gestational zinc or magnesium deficiency
image Prospective study of nutritional factors, blood pressure, and hypertension among US women.
image Association of macronutrients and energy intake with hypertension.
image Relations between magnesium, calcium, and plasma renin activity in black and white hypertensive patients
image Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat.
image Concentration of free intracellular magnesium in the myocardium of spontaneously hypertensive rats treated chronically with calcium antagonist or angiotensin converting enzyme inhibitor
image Nonpharmacologic treatment of hypertension.
image Micronutrient effects on blood pressure regulation.
image 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.
image Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).
image Effect of dietary magnesium supplementation on intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats.
image Electrolytes and hypertension: results from recent studies.
image Calcium antagonists in pregnancy as an antihypertensive and tocolytic agent
image The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.
image Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure.
image A prospective study of nutritional factors and hypertension among US men
image Electrolytes in the epidemiology, pathophysiology, and treatment of hypertension.
image Minerals and blood pressure.
image The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension.
image Attenuated vasodilator responses to Mg2+ in young patients with borderline hypertension.
image Dietary modulators of blood pressure in hypertension
image Daily intake of macro and trace elements in the diet. 4. Sodium, potassium, calcium, and magnesium
image Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.
image Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study.
image Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.
image Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium
image [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]
image Micronutrient profiles in HIV-1-infected heterosexual adults
image Fish oil and other nutritional adjuvants for treatment of congestive heart failure
image The use of oral magnesium in mild-to-moderate congestive heart failure
image Magnesium supplementation in patients with congestive heart failure
image Magnesium: A critical appreciation
image Significance of magnesium in congestive heart failure
image The rationale of magnesium as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy
image Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure: The relative importance of age, sex, and medical therapy
image The study of renal magnesium handling in chronic congestive heart failure
image Management of acute myocardial infarction in the elderly
image Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables
image [Magnesium: current studies--critical evaluation--consequences]
image Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart.
image [Value of magnesium in acute myocardial infarct]
image Concentrations of magnesium, calcium, potassium, and sodium in human heart muscle after acute myocardial infarction.
image [MAGNESIUM in cardiology]
image MAGNESIUM therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy
image [Oral MAGNESIUM supplementation to patients receivingdiuretics -- normalization of MAGNESIUM, POTASSIUM and sodium, and POTASSIUM pumps in the skeletal muscles].
image Effects of intravenous MAGNESIUM sulfate on arrhythmias in patients with congestive heart failure.
image MAGNESIUM-POTASSIUM interactions in cardiac arrhythmia. Examples of ionic medicine.
image Clinical clues to MAGNESIUM deficiency.
image Muscle and serum magnesium in pulmonary intensive care unit patients.
image Unrecognized pandemic subclinical diabetes of the affluent nations: Causes, cost and prevention
image Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy
image Different effects of Mg2+ on endothelin-1- and 5-hydroxytryptamine- elicited responses in goat cerebrovascular bed
image Ethanol-induced contraction of cerebral arteries in diverse mammals and its mechanism of action
image 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
image The case for intravenous magnesium treatment of arterial disease in general practice: Review of 34 years of experience
image Acute hypermagnesemia after laxative use
image Antacids drugs: Multiple but too often unknown pharmacological properties
image [Magnesium: current concepts of its physiopathology, clinical aspects and therapy]
image Bronchial reactivity and dietary antioxidants
image Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects
image Magnesium attenuates the neutrophil respiratory burst in adult asthmatic patients
image Physicochemical characterization of nedocromil bivalent metal salt hydrates. 1. Nedocromil magnesium
image Skeletal muscle magnesium and potassium in asthmatics treated with oral beta2-agonists
image Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium
image Magnesium in supraventricular and ventricular arrhythmias
image Ionic mechanisms of ischemia-related ventricular arrhythmias
image Trace elements in prognosis of myocardial infarction and sudden coronary death
image Magnesium flux during and after open heart operations in children.
image An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.
image Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.
image [Amyotrophic lateral sclerosis--causative role of trace elements]
image Aluminum Deposition in Central Nervous System of Patients with Amyotrophic Lateral Sclerosis From the Kii Peninsula of Japan
image [Deficiency of certain trace elements in children with hyperactivity]
image [Level of magnesium in blood serum in children from the province of Rzesz'ow]
image Frequently nebulized beta-agonists for asthma: effects on serum electrolytes.
image Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease.
image Calcium, phosphate, vitamin D, and the parathyroid
image Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome
image Rationales for micronutrient supplementation in diabetes.
image Comparison of the effects of magnesium hydroxide and a bulk laxative on lipids, carbohydrates, vitamins A and E, and minerals in geriatric hospital patients in the treatment of constipation.
image Small bowel obstruction caused by a medication bezoar: report of a case.
image Nonsustained polymorphous ventricular tachycardia during amiodarone therapy for atrial fibrillation complicating cardiomyopathy. Management with intravenous magnesium sulfate.
image The osmotic and intrinsic mechanisms of the pharmacological laxative action of oral high doses of magnesium sulphate. Importance of the release of digestive polypeptides and nitric oxide.
image Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy
image Effect of inhaled magnesium sulfate on sodium metabisulfite-induced Bronchoconstriction in asthma
image Magnesium sulfate therapy in certain emergency conditions
image Effect of intravenous magnesium sulphate on airway calibre and airway reactivity to histamine in asthmatic subjects
image Inhalation therapy with magnesium sulfate and salbutamol sulfate in bronchial asthma
image MgSO4 relaxes porcine airway smooth muscle by reducing Ca2+ entry
image Effect of intravenous magnesium sulfate on cardiac arrhythmias in critically III patients with low serum ionized magnesium
image The antiarrhythmic effects of taurine alone and in combination with magnesium sulfate on ischemia/reperfusion arrhythmia
image Magnesium taurate and fish oil for prevention of migraine.

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Magnesium supplementation in patients with congestive heart failure

Journal of the American College of Nutrition (USA), 1997, 16/1 (22-31)

Objective: To evaluate several potential clinical indicators of magnesium status (diet, blood, urine, 24-hour load retention) in patients with congestive heart failure before, during, and after oral magnesium supplementation. Methods: Twelve patients with New York Heart Association class II-III heart failure and 12 age and sex matched healthy control subjects were supplemented with 10.4 mmol oral magnesium lactate for 3 months. For the determination of magnesium status, samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium load retention study was performed before and 3 months after magnesium supplementation. A non-supplemented control group was similarly studied. Results: At baseline, magnesium intakes for all groups were below the RDA. No significant differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red cell magnesium concentrations among groups over time. At baseline 5/27 subjects (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal magnesium retentions (<25%). Magnesium excretions among groups were significantly different during supplementation. Percent magnesium retentions among groups were not different. Conclusions: Supplementation with 10.4 mmol oral magnesium daily for 3 months did not significantly alter blood levels or magnesium retention; however, patients demonstrated lower retention of magnesium after supplementation. Differences in magnesium retention was not related to basal magnesium intake, blood levels or excretion. Unfortunately, even an intensive effort at characterizing magnesium status did not identify a clinical indicator of utility for differentiating patients with congestive heart failure before, during, and after 3 months of magnesium supplementation.



Magnesium: A critical appreciation

Zeitschrift fur Kardiologie (Germany), 1996, 85/SUPPL. 6 (147-151)

The therapeutic efficacy of magnesium has been studied during recent years in a number of cardiovascular diseases: supraventricular and ventricular arrhythmias (multifocal atrial tachycardia, Torsade de pointes-tachycardia, glycoside-associated arrhythmias, sustained ventricular tachycardia), acute myocardial infarction, heart failure and arterial hypertension. Although only a few of these arrhythmias were studied under controlled conditions, the therapeutic efficacy of intravenous magnesium given in a high dose in these arrhythmias seems to be established. By contrary, the efficacy of magnesium in acute myocardial infarction, congestive heart failure and arterial hypertension remains controversial up to now. Magnesium cannot be regarded as standard therapy for example for patients with acute myocardial infarction.



Significance of magnesium in congestive heart failure

American Heart Journal (USA), 1996, 132/3 (664-671)

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents <1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.



The rationale of magnesium as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy

American Heart Journal (USA), 1996, 132/2 II (483-486)

Only one third of hospitalized patients with acute myocardial infarction receive thrombolytic therapy despite its proven benefits on outcomes. Elderly patients, for example, have a greater risk cf death after myocardial infarction, but studies demonstrate that thrombolytic therapy is less likely to be used in older patients. Intravenous magnesium supplementation, both theoretically and experimentally, has been demonstrated to decrease myocardial damage and reduce the mortality rate in subsets of patients, including the elderly and/or patients not suitable for thrombolysis, if it is administered before reperfusion occurs. The aim of this study is to review the rationale of magnesium supplementation as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy.



Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure: The relative importance of age, sex, and medical therapy

Archives of Internal Medicine (USA), 1996, 156/15 (1669-1673)

Objective: To define contemporary patterns of risk and management among patients with congestive heart failure (CHF). Methods: Cross-sectional records audit of 4606 hospitalized patients with CHF in 1992 and 1993. Results: Overall medication use was diuretics, 82%; angiotensin-converting enzyme inhibitors, 53%; nitrates, 49%; digoxin, 46%; potassium, 40%; acetylsalicylic acid, 36%; calcium antagonists, 20%; warfarin, 17%; beta- blockers, 15%; and magnesium, 10%. Angiotensin-converting enzyme inhibitors were used less frequently in women and patients 70 years or older (P<.01). Total in-hospital mortality was 19%. The most common single cause of death was CHF progression, but noncardiac causes accounted for 30% of all deaths. Logistic regression analysis revealed age 70 years or older and the use of magnesium and nitrates to be associated with increased relative risk of in- hospital mortality; angiotensin-converting enzyme inhibitors, acetylsalicylic acid, calcium antagonists, beta-blockers, and warfarin were associated with decreased risk. Conclusions: Hospitalized patients with CHF have high all-cause mortality risk and less than optimal use of proven efficacious therapy, particularly among women and the elderly. Increased use of proven CHF therapy would likely decrease the risk of cardiac events, but the competing noncardiac risks in this patient population are high and may not be affected by improved use of efficacious cardiac therapies.



The study of renal magnesium handling in chronic congestive heart failure

Sapporo Medical Journal (Japan), 1996, 65/1 (23-32)

It is now known that the serum magnesium level is low in patients with chronic congestive heart failure (CHF). In this study, to clarify the role of renal magnesium handling in CHF, the following parameters were examined in normal subjects (control: n = 28) and patients with CHF (n = 37): serum magnesium (s-Mg), plasma aldosterone concentration (PAC), endogenous creatinine clearance (C(Cr)), urinary excretions of magnesium (U(Mg)V) and sodium (U(Na)V), and fractional excretions of magnesium (FE(Mg)), sodium (FE(Na)) and potassium (FE(K)). The relationship between s-Mg and the severity of cardiac dysfunction (NYHA subclass in CHF) was also investigated in CHF. All subjects were admitted to our hospital and given a standard diet including 120 mEq of Na and 75 mEq of K/day, and all the parameters were measured in the early morning after an overnight fast. Compared with the controls, the patients with CHF showed lower levels of s-Mg, C(Cr), U(Na)V and FE(Na), and higher levels of FE(Mg) and PAC. On the other hand, there was no significant difference in U(Mg)V between the controls and CHF patients. In both groups, significant positive correlations were observed between U(Mg)V and FE(Mg), and between U(Mg)V and C(Cr). FE(Mg) correlated positively with FE(K) and PAC in patients with CHF, suggesting an important role of mineralocorticoids in magnesium handling in the distal renal tubules. In the severe CHF (NYHA II or III) subgroup, levels of s-Mg and FE(Mg) were quite similar to those in the mild CHF (NYHA I) subgroup, but the severe CHF subgroup used potassium-magnesium sparing drugs (spironolactone, triamterene and angiotensin converting enzyme inhibitor) more frequently. In CHF patients, combined use of loop diuretics and potassium-magnesium sparing drugs did not show any significant influence on the levels of s-Mg and FE(Mg). These results suggest that the low level of s-Mg in CHF patients is attributable to enhancement of renal magnesium excretion by secondary aldosteronism, and that use of potassium-magnesium sparing drugs may be beneficial for prevention of magnesium deficiency in CHF.



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.



[Magnesium: current studies--critical evaluation--consequences]

Z Kardiol (GERMANY) 1996, 85 Suppl 6 p147-51

The therapeutic efficacy of magnesium has been studied during recent years in a number of cardiovascular diseases: supraventricular and ventricular arrhythmias (multifocal atrial tachycardia, Torsade de pointes-tachycardia, glycoside-associated arrhythmias, sustained ventricular tachycardia), acute myocardial infarction, heart failure and arterial hypertension. Although only a few of these arrhythmias were studied under controlled conditions, the therapeutic efficacy of intravenous magnesium given in a high dose in these arrhythmias seems to be established. By contrary, the efficacy of magnesium in acute myocardial infarction, congestive heart failure and arterial hypertension remains controversial up to now. Magnesium cannot be regarded as standard therapy for example for patients with acute myocardial infarction. (13 Refs.)



Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart.

Int J Biochem Cell Biol (ENGLAND) Jan 1997, 29 (1) p129-34

Magnesium deficiency is known to produce a cardiomyopathy, characterised by myocardial necrosis and fibrosis. As part of the ongoing investigations in this laboratory to establish the biochemical correlates of these histological changes, the present study probed the extent of lipid peroxidation and alterations in collagen metabolism in the heart in rats fed a magnesium-deficient diet for 28, 60 or 80 days. While lipid peroxidation was measured by the thiobarbituric acid reaction, collagen turnover rates and fibroblast proliferation were assessed using [3H]-proline and [3H]-thymidine, respectively. Tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. A 39% increase in the cardiac tissue level of thiobarbituric acid reactive substances was observed on day 60 of deficiency (p < 0.001). A marked drop in collagen deposition rate (59%, p < 0.001%) on day 28 but a significant rise in fractional synthesis rate (12%, p < 0.001) and collagen deposition rate (24%, p < 0.001) on day 60 were observed. A fibroproliferative response in the heart was evident on day 80 but not at earlier time-points. Thus, the present study provides evidence of increased lipid peroxidation and net deposition of collagen in the myocardium in response to dietary deficiency of magnesium. These changes were, however, not directly related to alterations in the tissue levels of Mg. It is suggested that the increase in cardiac collagen synthesis and fibroplasia associated with Mg deficiency may represent reparative fibrogenesis, upon oxidative damage to the cardiac muscle, and is mediated by a mechanism independent of changes in cardiac tissue levels of Mg.



[Value of magnesium in acute myocardial infarct]

Z Kardiol (GERMANY) 1996, 85 Suppl 6 p129-34

Experiments in animal models of myocardial infarction have provided evidence that early magnesium infusion can limit the infarct size. One mechanism that has been postulated to be of importance is a protection of the cardiomyocyte against a calcium overload during or after ischemia. We had shown that in isolated human myocytes from patient with ischemic cardiomyopathy an increase of the extracellular magnesium concentration could block the L-type-calcium current in a dose dependent manner. Until recently only small, uncontrolled studies have indicated there may be a reduction of mortality due to myocardial infarction when intravenous magnesium infusion was added to standard therapy. However, two recently published randomized studies showed different results, although similar doses of magnesium were used (70-80 mmol magnesium over 24 h). The LIMIT-2-study was a double-blind, placebo controlled investigation of over 2300 patients with suspected myocardial infarction. Magnesium infusion was associated with a reduction of the 28 day mortality by 24%. The ISIS-4-study on over 50,000 patients with suspected myocardial infarction did not show any positive effect of magnesium on mortality. Major differences between both studies were differences in thrombolysis (LIMIT-2:1/3, ISIS-4: 70%). Furthermore, in LIMIT-2 magnesium infusion was started as early as possible, whereas in ISIS-4 magnesium was given after the end of thrombolytic therapy. In can be concluded that magnesium therapy in acute myocardial infarction after thrombolytic therapy is not useful. However, in patients where thrombolytic therapy is not feasable, early infusion of magnesium may be beneficial. As side effects are minor and costs are low, a therapeutic trial may be warranted, although a final decision on the effects of magnesium cannot be made. (15 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.



[MAGNESIUM in cardiology]

Schweiz Rundsch Med Prax (SWITZERLAND) May 2 1995, 84 (18) p526-32

MAGNESIUM acts as a cofactor of numerous enzymes and is important for the maintenance of a high intracellular POTASSIUM concentration and the transmembrane action potential. Of the total MAGNESIUM content of about 1000 mmol, only 0.3% are located in plasma. Hypomagnesemia and probable MAGNESIUM deficiency are found in 7 to 11% of hospitalized patients but are only rarely accompanied by relevant clinical symptoms. Prolonged diuretic therapy and secondary aldosteronism are frequent causes of hypomagnesemia in cardiology. Intravenous MAGNESIUM is a vasodilatator and prolongs the AH interval. In animal studies MAGNESIUM has been shown to have cardioprotective and platelet-inhibiting properties. The only verified indication for intravenous MAGNESIUM is the initial treatment of torsade de pointes. MAGNESIUM may suppress digitalis-induced tachyarrhythmias and convert paroxysmal supraventricular tachycardia and monomorphic ventricular tachycardia to sinus rhythm. Its role in the treatment of acute myocardial infarction and of ventricular arrhythmias in congestive heart failure is unclear. (81 Refs.)



MAGNESIUM therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy

J Cardiol (UNITED STATES) Feb 15 1995, 75 (5) p321-3

Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that MAGNESIUM sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of MAGNESIUM sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous MAGNESIUM sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous MAGNESIUM. Group II consisted of 98 patients who received isotonic glucose as a placebo. MAGNESIUM reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received MAGNESIUM sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving MAGNESIUM sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, MAGNESIUM sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI.



[Oral MAGNESIUM supplementation to patients receivingdiuretics -- normalization of MAGNESIUM, POTASSIUM and sodium, and POTASSIUM pumps in the skeletal muscles].

Ugeskr Laeger (DENMARK) Jul 4 1994, 156 (27) p4007-10, 4013

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of MAGNESIUM, POTASSIUM, and sodium-POTASSIUM pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle MAGNESIUM and/or POTASSIUM below the control level received oral MAGNESIUM hydroxide supplement for 2-12 weeks (N = 20) or 26 weeks (N = 16). After short term (2-12 weeks) MAGNESIUM supplementation muscle parameters were increased, but far from normalized. After MAGNESIUM supplementation for 26 weeks, the muscle concentrations of MAGNESIUM, POTASSIUM and sodium-POTASSIUM pumps were normalized in most cases. Oral MAGNESIUM supplementation may restore diuretic-induced disturbances in the concentrations of MAGNESIUM, POTASSIUM and sodium-POTASSIUM pumps in skeletal muscle. A supplemental period of at least six months seems required before complete normalization can be expected.



Effects of intravenous MAGNESIUM sulfate on arrhythmias in patients with congestive heart failure.

Am Heart J (UNITED STATES) Jun 1993, 125 (6) p1645-50

Intravenous MAGNESIUM is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum MAGNESIUM concentrations are associated with frequent arrhythmias and high mortality. This suggests that MAGNESIUM administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous MAGNESIUM infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum MAGNESIUM < or = 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in MAGNESIUM concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 +/207 hr-1 in patients in whom serum MAGNESIUM concentration increased > or = 0.75 mg/dl, but increased by 72 +/- 393 hr-1 in patients with a change < 0.75 mg/dl (p < 0.05). For all patients, the frequency of premature ventricular depolarizations was 283 +/- 340 hr-1 pretreatment and 220 +/269 hr-1 following MAGNESIUM infusion (p = 0.21). Patients with > or = 300 premature ventricular depolarizations hr-1 demonstrated a decrease from 794 +/- 309 to 369 +/- 223 hr-1 (p < 0.001). Intravenous MAGNESIUM administration decreased the frequency of couplets from 233 +/- 505 to 84 +/- 140 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)



MAGNESIUM-POTASSIUM interactions in cardiac arrhythmia. Examples of ionic medicine.

Magnes Trace Elem (SWITZERLAND) 92 1991, 10 (2-4) p193-204

Ionic biology involving Ca2+, Na+, K+ and Mg2+ across the cell membrane and in the development of the action potential is reviewed with reference to cardiac arrhythmia. K+ and Mg2+ deficiency which frequently occur together lead to abnormal ionic transfer of Na+, K+ and Ca2+ with development of automaticity, triggered impulses and reentrant tachycardia. Tachycardia occurring in acute myocardial ischemia, congestive heart failure, hypertensives on diuretics and digitalis toxicity is examined according to the concept of ionic imbalance. A protocol for prevention and treatment of cardiac tachyarrhythmia is proposed with this concept in mind.



Clinical clues to MAGNESIUM deficiency.

Isr J Med Sci (ISRAEL) Dec 1987, 23 (12) p1238-41

Two cases of congestive heart failure with coexistent MAGNESIUM and POTASSIUM depletion are described. The prolonged QTc intervals and ventricular premature beats of the first patient and the idionodal tachycardia of the second patient disappeared only after MAGNESIUM repletion, which normalized both extra- and intracellular POTASSIUM and MAGNESIUM levels. The third patient had a case of urosepsis while on total parenteral nutrition. He developed diarrhea, hypocalcemia, hypokalemia, hypomagnesemia, weakness, muscular fasciculations and athetoid movements. The neurological manifestations were relieved and the biochemical abnormalities normalized only after MAGNESIUM repletion.



Muscle and serum magnesium in pulmonary intensive care unit patients.

Crit Care Med (UNITED STATES) Aug 1988, 16 (8) p751-60

Muscle specimens by means of quadriceps femoris needle biopsy and blood samples were obtained in 32 patients consecutively admitted to a pulmonary ICU for chronic obstructive pulmonary disease and acute respiratory failure, and in 30 age and sex-matched healthy control subjects. Muscle magnesium (Mg) and potassium (K) content was assessed by atomic absorption spectrophotometry; serum electrolytes were also measured. The presence of clinical and biochemical correlates of low serum and muscle Mg was investigated. Three (9.4%) out of 32 patients had hypomagnesemia (Mgs less than or equal to 0.7 mmol/L) with normal muscle Mg values, whereas low muscle Mg values were found in 15 (47%) of 32 patients, with no alterations of serum Mg levels. Muscle Mg was decreased significantly in pulmonary ICU patients as compared to control subjects. No significant correlation was present between serum and muscle Mg, or between serum and muscle K. Significant relationships between muscle Mg and both muscle and intracellular K concentrations were also found. Lower values for muscle and intracellular K and a higher incidence of both more prolonged ICU stays and ventricular extrasystolic beats characterized the ICU patients with altered muscle Mg levels. We conclude that, given the serious complications of Mg metabolism derangements, the presence of altered cell Mg content should be taken into account in pulmonary ICU patients. Moreover, in these patients, serum Mg levels are of little value in the diagnosis of intracellular Mg deficits.



Unrecognized pandemic subclinical diabetes of the affluent nations: Causes, cost and prevention

Journal of Orthomolecular Medicine (Canada), 1996, 11/2 (95-99)

Regarding populations on the industrialized 'western affluent diet', arguments are made that: (1) plasma glucose values commonly seen and accepted as normal are abnormal; (2) their glucose tolerance is innately unstable; (3) most of their morbidity and mortality is produced by hyperglycemia far below glycosuria and/or arteriosclerosis which can occur independently or together; (4) simple low cost methods for preventing and treating both have been in the literature for decades (correction of the sugar, fat and protein excesses; and controlled supplementation of pyridoxine (vitamin B6). Mg, Cr and coenzyme Q10); and (5) these lessons were missed by main stream medicine because of the vast size of the literature, enforcement of 'treatment of choice', and lack of computer aided diagnosis. Cited as striking evidence of this tragic situation is the failure of mainstream clinical medicine to understand the cause of the remarkable decline in CVD in the 1960s and 1970s that followed U.S. enrichment of cereals with pyridoxine (vitamin B6). Recommendations are made for correction of unnecessary costly delays between publication and implementation of such research findings.



Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy

Journal of the American College of Nutrition (USA), 1996, 15/1 (14-20)

There is an increased requirement for nutrients in normal pregnancy, not only due to increased demand, but also increased loss. There is also an increased insulin resistant state during pregnancy mediated by the placental anti-insulin hormones estrogen, progesterone, human somatomammotropin; the pituitary hormone prolactin; and the adrenal hormone, cortisol. If the maternal pancreas cannot increase production of insulin to sustain normoglycemia despite these anti-insulin hormones, gestational diabetes occurs. Gestational diabetes is associated with excessive nutrient losses due to glycosuria. Specific nutrient deficiencies of chromium, magnesium, potassium and pyridoxine may potentiate the tendency towards hyperglycemia in gestational diabetic women because each of these four deficiencies causes impairment of pancreatic insulin production. This review describes the pathophysiology of the hyperglycemia and the nutrient loss in gestational diabetes and further postulates the mechanism whereby vitamin/mineral supplementation may be useful to prevent or ameliorate pregnancy-related glucose intolerance.



Different effects of Mg2+ on endothelin-1- and 5-hydroxytryptamine- elicited responses in goat cerebrovascular bed

J. CARDIOVASC. PHARMACOL. (USA), 1994, 23/6 (1004-1010)

Mg2+ influences the response of cerebral arteries to several agonists, but until now its effects on endothelin-1 (ET-1) had not been studied. We recorded and compared the responses of goat cerebrovascular bed to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in isolated goat middle cerebral arteries and in vivo by recording cerebral blood flow (CBF) and other physiologic parameters in conscious goats. Cumulative addition of ET-1 (10-101-3 x 10-8M) and 5-HT (10-9-10-5M) contracted cerebral arteries concentration dependently in bath media containing 0 (Mg2+ free medium), 1 (control), and 10 mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased sensitivity (EC50) and Mg2+ overload reduced contractility (E(max)) of cerebral arteries to 5-HT, whereas the ET-1 response did not change in these conditions. Cumulative addition of Mg2+ (10-4-3 x 10-2M) at the active tone induced by ET-1 (10-9M) and 5-HT (10-5M) elicited concentration-dependent relaxations of cerebral arteries, but the relaxant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 microg/min) directly into the cerebroarterial supply of the unanesthetized goats elicited a sustained decrease in CBF and an increase in cerebral vascular resistance. Magnesium sulfate, administered as increasing doses (10-300 mg) in the same way increased CBF and decreased cerebral vascular resistance, although this effect was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction. When infused intravenously (i.v.; 3 g/15 min), magnesium sulfate had no effect on the ET-1-induced cerebral vasoconstriction, but increased 5-HT-reduced CBF. ET-1 is a relatively Mg2+-resistant contractile stimulus in the cerebrovascular bed. This should be taken into account in consideration of the therapeutic potential of Mg2+ in cerebrovascular disorders in which ET-1 might be involved.



Ethanol-induced contraction of cerebral arteries in diverse mammals and its mechanism of action

EUR. J. PHARMACOL. ENVIRON. TOXICOL. PHARMACOL. SECT. (Netherlands), 41993, 248/3 (229-236)

Acute ethanol exposure (8-570 mM) induced potent contractile responses of rings in both basilar and middle cerebral arteries, from dogs, sheep, piglets and baboons, in a dose-dependent manner. The contractions were reproducible and not tachyphylactic. The middle cerebral arteries were found to be more sensitive to ethanol than the basilar arteries. No known pharmacological antagonist, tested, exerted any effects on ethanol-induced contractions. No differences in responsiveness to ethanol in canine arteries were found between male and female animals or between the presence and the absence of endothelial cells. Removal of extracellular Ca2+ ((Ca2+)0) partially attenuated ethanol-induced contractions, while withdrawal of extracellular Mg2+ ((Mg2+)0) potentiated such contractions. In the complete absence of (Ca2+)0, caffeine and ethanol induced similar, transient contractions followed by relaxation in K+-depolarized cerebral vascular tissue. Ethanol-induced contractions were completely abolished by pretreatment of tissues with caffeine. Our results suggest that: (a) acute ethanol intoxication can induce direct contractions (independent of amine, prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues, including those from primates; (b) these contractile responses are heterogeneous along the cerebrovascular tree and independent of endothelial cells; (c) in addition to a need for (Ca2+)0, an intracellular release of Ca2+ is needed for ethanol to induce contractions; and (d) hypomagnesemia or Mg deficiency potentiates the contractile effects of ethanol on brain vessels and may be a risk factor for ethanol-related, ischemic stroke events.



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.



The case for intravenous magnesium treatment of arterial disease in general practice: Review of 34 years of experience

J. NUTR. MED. (United Kingdom), 1994, 4/2 (169-177)

Magnesium sulphate (MgSO4) in a 50% solution was injected initially intramuscularly and later intravenously into patients with peripheral vascular disease (including gangrene, claudication, leg ulcers and thrombophlebitis), angina, acute myocardial infarction (AMI), non-haemorrhagic cerebral vascular disease and congestive cardiac failure. A powerful vasodilator effect with marked flushing was noted after intravenous (IV) injection of 4-12 mmol of magnesium (Mg) and excellent therapeutic results were noted in all forms of arterial disease. This technique of rapidly securing very high initial blood levels of MgSO4 produces results in arterial disease which cannot be equalled by oral vasodilators or intramuscular (IM) or IV infusion therapy. It is suggested that the most important action of MgSO4 in AMI is to open up collateral circulation and relieve ischaemia thus reducing infarct size and mortality rates. Prophylactic use of MgSO4 and its effect on serum lipid, fibrinogen, urea and creatinine levels are discussed.



Acute hypermagnesemia after laxative use

Annals of Emergency Medicine (USA), 1996, 28/5 (552-555)

We present the case of a patient in whom hypotension, sudden cardiopulmonary arrest, and coma developed after a massive dose of a seemingly harmless cathartic agent. The diagnosis of hypermagnesemia was made 9 hours after the patient's admission, when the serum magnesium concentration was 21.7 mg/dL (8.9 mmol/L). The patient's condition improved with IV calcium, saline solution infusion, and cardiorespiratory support. The elimination half-life of magnesium in this case was 27.7 hours. Few cases have been reported in which patients have survived with serum levels greater than 18 mg/dL (7.4 mmol/L). This case provides evidence that hypermagnesemia may occur in patients with normal kidney function. The diagnosis of hypermagnesemia should be considered in patients who present with symptoms of hyporeflexia, lethargy, refractory hypotension, shock, prolonged QT interval, respiratory depression, or cardiac arrest.



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.



[Magnesium: current concepts of its physiopathology, clinical aspects and therapy]

Acta Vitaminol Enzymol (ITALY) 1982, 4 (1-2) p87-97

Functional constipation is not a life-threatening disease, but as a chronic state it worries the patient and causes him discomfort and often leads him to self-medication with potentially dangerous drugs. Ro 01-4709 contains as active substance dexpanthenol, which is the alcohol of pantothenic acid, a vitamin of the B-complex. In the cells, dexpanthenol is readily oxidized to pantothenic acid, which stimulates peristalsis when administered in therapeutically effective doses. Ro 01-4709 has already proven its efficacy in the prevention and treatment of adynamic ileus. Recently, several open and two double-blind studies have been carried out, investigating the efficacy of oral Ro 01-4709 in the treatment of chronic functional constipation. The two double-blind studies showed Ro 01-4709 to be superior to placebo in all parameters measured. The studies with an open design also demonstrated a favourable effect of Ro 01-4709 in the treatment of chronic functional constipation. Owing to its physiological action-which is in a favourable contrast to that of normal laxatives. Ro 01-4709 can be recommended for the treatment of functional constipation in pregnant women, children and the elderly.



Bronchial reactivity and dietary antioxidants

Thorax (United Kingdom), 1997, 52/2 (166-170)

Background - It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. Methods - The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. Results - Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than five-fold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. Conclusions - This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.



Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects

Clinical and Experimental Allergy (United Kingdom), 1997, 27/5 (546-551)

Background: Magnesium is a cation with smooth muscle relaxant and anti- inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. Objective: To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate (AMP)) in asthmatic subjects. Methods: Two separate randomized, double blind, placebo controlled crossover studies. each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results: In the histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22- 1.82) doubling doses at 5 min (P=0.018), and 1.0 (0.3-1.7) doubling doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also significantly lower at 5 min after magnesium than alter saline, by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this difference was not statistically signifle; clinical article; clinical trial; randomized controlled trial; double blind procedure; crossover procedure; controlled study; adult; inhalational drug administration; article; priority journal



Magnesium attenuates the neutrophil respiratory burst in adult asthmatic patients

Academic Emergency Medicine (USA), 1996, 3/12 (1093-1097)

Introduction: IV magnesium (Mg2+) has been proposed as an emergent treatment for acute asthma exacerbations. Recent studies have focused on the effects of Mg2+ on bronchial smooth muscle, yet asthma is primarily an inflammatory disease. Objective: To assess the effects of Mg2+ on the neutrophil respiratory burst of adult patients with asthma. Methods: A prospective, blind study of volunteer adult asthmatic patients was performed. The patients' polymorphonuclear neutrophils (PMNs) were isolated, purified, and placed into phosphate-buffered saline with the following test conditions: concentrations of magnesium chloride (MgCl2) added: 0 mmol MgCl2, 1 mmol MgCl2 (low), and 10 mmol MgCl2 (high) both with and without the calcium (Ca2+) ionophore A23187 (0.1 mmol). PMNs were activated using N-formyl- methionyl-leucyl-phenylalanine (fMLP) (10 micromol), and the production of superoxide (O2/-) was measured by the spectrophotometric reduction of cytochrome c. Results: Mg2+ reduced activated PMN O2/- production compared with that for no Mg2+ (1.0 plus or minus 0.1 nmol O2/-/5 x 105 PMN/min) in both low (-0.52* plus or minus 0.3 nmol O2/-/5 x 105 PMN/min) and high (-0.76* plus or minus 0.3 nmol O2/-/5 x 105 PMN/min; *p < 0.05) concentrations. The addition of A23187 increased O2/- production in both the high (0.53* plus or minus 0.02 nmol O2/-/5 x 105 PMN/min) and the low (1.5* plus or minus 0.6 nmol O2/-/5 x 105 PMN/min) Mg2+ groups, with no change in the control group (1.2 plus or minus 0.2 nmol O2/-/105 PMN/min). Conclusions: In clinically relevant concentrations, Mg2+ attenuates the neutrophil respiratory burst in adult asthmatic patients. Mg2+ appears to affect PMNs by interfering with extracellular Ca2+ influx. Mg2+ may have a beneficial anti-inflammatory effect in asthmatic individuals.



Physicochemical characterization of nedocromil bivalent metal salt hydrates. 1. Nedocromil magnesium

Journal of Pharmaceutical Sciences (USA), 1996, 85/10 (1026-1034)

Nedocromil sodium is used in the treatment of reversible obstructive airways diseases, such as asthma. The physicochemical, mechanical, and biological characteristics of nedocromil sodium can be altered by its conversion to other salt forms. In this study, three crystalline hydrates, the pentahydrate, heptahydrate, and decahydrate, of a bivalent metal salt, nedocromil magnesium (NM), were prepared. The relationships between these hydrates were studied through their characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Karl Fischer titrimetry (KFT), hot stage microscopy (HSM), ambient or variable temperature powder X- ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy (SEM), water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR), and solubility measurements. The pentahydrate showed two dehydration steps, corresponding to two binding states of water, a more temperature-sensitive tetramer and a more stable monomer, deduced from the crystal structure previously determined. The heptahydrate and decahydrate each showed a dehydration step with a minor change in slope at about 50 degreeC, which was analyzed by derivative TGA and confirmed by DSC. HSM and variable temperature PXRD also confirmed the thermal dehydration behavior of the NM hydrates. The decahydrate underwent an apparently irreversible phase transformation to the pentahydrate at 75 degreeC at an elevated water vapor pressure. The PXRD, FTIR, and SSNMR of the decahydrate were similar to those of the heptahydrate, suggesting that the three extra water molecules in the decahydrate are loosely bound, but were significantly different from those of the pentahydrate. The rank order of both IDR and solubility in water at 25 degreeC was heptahydrate similar decahydrate > pentahydrate, corresponding to the rank order of free energy with respect to the aqueous solution.



Skeletal muscle magnesium and potassium in asthmatics treated with oral beta2-agonists

European Respiratory Journal (Denmark), 1996, 9/2 (237-240)

Dietary magnesium has been shown to be important for lung function and bronchial reactivity. Interest in electrolytes in asthma has so far mainly been focused upon serum potassium, especially linked to beta2-agonist treatment. It is known that serum levels of magnesium and potassium may not correctly reflect the intracellular status. We therefore investigated whether asthmatics treated with oral beta2-agonists had low magnesium or potassium in skeletal muscle and serum, and whether withdrawal of the oral beta2-agonists would improve the electrolyte levels. Magnesium and potassium levels in skeletal muscle biopsies, serum and urine were analysed in 20 asthmatics before and 2 months after withdrawal of long-term oral beta2-agonists, and for comparison in 10 healthy subjects. Skeletal muscle magnesium in the asthmatics was lower both before (3.62plus or minus0.69 mmol-100 g-1 (meanplus or minusSD)) and after (3.43plus or minus0.60 mmol.100 g-1) withdrawal of oral beta2-agonists compared with the controls (4.43plus or minus0.74 mmol-100 g-1) Skeletal muscle potassium and serum magnesium did not differ between the groups. Serum potassium was significantly lower both before (4.0plus or minus0.2 mmol.L-1) and after (3.9plus or minus0.2 mmol.L-1) the withdrawal of oral beta2-agonists compared with the control group (42plus or minus0.2 mmol.L-1). The asthmatics had lower skeletal muscle magnesium and lower serum potassium than the healthy controls, both with and without oral beta2-agonists. Whether the findings are related to asthma pathophysiology or treatment is currently being investigated.

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