Clinical studies with the NOVA ISE for IMg2+.

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.

Effect of Candida albicans plus histamine on prostaglandin E2 production by peripheral blood mononuclear cells from healthy women and women with recurrent candidal vaginitis.

The in vitro production of prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) in response to viable Candida albicans, histamine, and C. albicans plus histamine was examined. With PBMC from 10 healthy women, C. albicans but not histamine induced PGE2 at a low level (100 pg/ml). However, C. albicans plus histamine acted synergistically to stimulate PGE2 production (448 pg/ml). PBMC from 8 of 10 women with recurrent candidal vaginitis also produced maximal levels of PGE2 in the presence of C. albicans plus histamine. Production of tumor necrosis factor by PBMC from patients and controls was unaffected by histamine in both the presence and absence of C. albicans. However, unlike the controls, PBMC from six of the patients who were atopic and from two nonatopic patients spontaneously released PGE2 in vitro. Addition of 4 or 10 units/ml interferon-gamma inhibited spontaneous and C. albicans-induced PGE2 production by PBMC. These data reinforce the evidence that immediate hypersensitivity responses may be involved in the etiology of recurrent candidal vaginitis.

Magnesium, stress and neuropsychiatric disorders.

Magnesium has a profound effect on neural excitability; the most characteristic signs and symptoms of Mg deficiency are produced by neural and neuromuscular hyperexcitability. These create a constellation of clinical findings termed tetany syndrome (TS). TS symptoms include muscle spasms, cramps and hyperarousal, hyperventilation and asthenia. Physical signs (Chvostek's, Trousseau's or von Bonsdorff's) and abnormalities of the electromyogram or electroencephalogram can usually be elicited. Signs and symptoms of TS are frequently encountered in clinical practice, especially among patients with functional or stress-related disorders. The role of Mg deficit in TS is suggested by relatively low levels of serum or erythrocyte Mg and by the clinical response to oral Mg salts, which has been demonstrated in controlled studies. Among the more serious neurologic sequelae of TS are migraine attacks, transient ischemic attacks, sensorineural hearing loss and convulsions. Mg deficiency may predispose to hyperventilation and may sensitize the cerebral vasculature to the effects of hypocarbia. Mg deficiency increases susceptibility to the physiologic damage produced by stress, and Mg administration has a protective effect; studies on noise stress and noise-induced hearing loss are taken as an example. In addition, the adrenergic effects of psychological stress induce a shift of Mg from the intracellular to the extracellular space, increasing urinary excretion and eventually depleting body stores. Drugs used in neurology and psychiatry may affect Mg levels in blood and may diminish signs of tetany, making assessment of Mg status more difficult. Pharmacologic use of Mg can decrease neurologic deficit in experimental head trauma, possibly by blockade of N-methyl-D-aspartate receptors. In conjunction with high doses of pyridoxine, Mg salts benefit 40% of patients with autism, possibly by an effect on dopamine metabolism.

Magnesium and inflammatory bowel disease.

Mg deficiency is a frequent complication of inflammatory bowel disease (IBD) demonstrated in 13-88% of patients. Decreased oral intake, malabsorption and increased intestinal losses are the major causes of Mg deficiency. The complications of Mg deficiency include: cramps, bone pain, delirium, acute crises of tetany, fatigue, depression, cardiac abnormalities, urolithiasis, impaired healing and colonic motility disorders. Serum Mg is an insensitive index of Mg status in IBD. Twenty-four-hour urinary excretion of Mg is a sensitive index and should be monitored periodically. Parenteral Mg requirements in patients with IBD are at least 120 mg/day or more depending upon fecal or stomal losses. Oral requirements may be as great as 700 mg/day depending on the severity of malabsorption.

Magnesium and immune function: an overview.

Mg participates in immune responses in numerous ways: as a cofactor for immunoglobulin synthesis, C'3 convertase, immune cell adherence, antibody-dependent cytolysis, IgM lymphocyte binding, macrophage response to lymphokines, T helper-B cell adherence, binding of substance P to lymphoblasts and antigen binding to macrophage RNA. Mg deficiency in rodents impairs IgG synthesis and cell-mediated immunity; complications include thymus atrophy, elevated IgE, hypereosinophilia, histaminosis and lymphoma. Immunologic sequelae of Mg deficiency in humans are subtle and may be affected by genetic control of blood cell Mg concentration. Abnormal C' activation, excess antibody production and susceptibility to allergy and to chronic fungal and viral infections have been reported. Mg appears to play a protective role in acute allergic reactions.

Biochemical abnormalities in patients with multiple chemical sensitivities.

Patients with MCS show numerous physiological and biochemical abnormalities and are generally sicker than a control group of allergic patients. Associated with MCS are mitral valve prolapse, hypothyroidism, autoimmune thyroiditis, specific abnormalities of amino acid and essential fatty acid metabolism, and diminished activity of ESOD and EGPx. Equally prevalent among MCS patients and controls are deficiencies of magnesium and Vitamin B6. Since patients with MCS feel sick almost all of the time, it is likely that some of these abnormalities contribute to their general level of ill health, if not to their sensitivities. It is also possible that these various abnormalities are caused by some unidentified fundamental metabolic or neuroendocrine disturbance that is common to states of hypersensitivity. A provocative finding is the high frequency with which impaired anti-oxidant levels were detected. Erythrocyte activity of SOD was low in 89% and EGPx was low in 48% of MCS patients. Furthermore, 41% showed impaired excretion of essential amino acids, despite a high protein diet, and leucocyte vitamin C was low in the 5 patients not taking vitamin C supplements. Anti-oxidant deficiences may certainly contribute to hypersensitivity to environmental pollutants and toxic chemicals. In fact, treatment with anti-oxidants, including selenium, vitamin C, copper, zinc, and sulfur-containing amino acids was associated with major clinical improvement in 14 (25%) of the patients in the MCS group and with limited relief of symptoms in another 10 (18%). In all patients in whom ESOD or EGPx were repeated, improvement in levels was observed following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium deficiency in the pathogenesis of mitral valve prolapse.

Idiopathic mitral valve prolapse (MVP) is the commonest valvular disorder in industrialized nations. It is predominantly a familial condition, showing Mendelian dominance with delayed and variable penetrance. Although hyperkinesis and hypertrophy of the left ventricle have been described in MVP, its histopathology, somatic morphology and genetics support the leading theory that MVP results from a hereditary disorder of connective tissue. Latent tetany (LT) due to chronic Mg deficit (Mg-D) occurs in over 85% of MVP cases; MVP complicates 26% of LT. Mg-D can explain many clinical features of the MVP syndrome which are not easily explained by its genetics. Mg-D hinders the mechanism by which fibroblasts degrade defective collagen, increases circulating catecholamines, predisposes to cardiac arrhythmias, thromboembolic phenomena and dysregulation of the immune and autonomic nervous systems. Mg therapy provides relief of MVP symptoms.

Increased requirements for essential fatty acids in atopic individuals: a review with clinical descriptions.

Patients with atopic eczema and a mixture of allergic illnesses show biochemical evidence suggesting impairment in the desaturation of linoleic acid and linolenic acid by the enzyme delta-6 dehydrogenase. Consequences of this enzyme defect are 1) diminished synthesis of the 20-carbon polyunsaturated fatty acids, which are prostaglandin precursors and 2) a reduction in the concentration of double bonds in the cell membrane. A distortion in the production of prostaglandins and leukotrienes, which might result from this block, can account for the immunological defects of atopy and a variety of clinical symptoms experienced by atopic individuals. Dietary supplementation with essential fatty acids relieves the signs and symptoms of atopic eczema, may improve other types of allergic inflammation, and may also correct coexisting symptoms as diverse as excessive thirst and dysmenorrhea. Further research is suggested to test the hypothesis that some atopic states represent a condition of essential fatty acid dependency owing to defective desaturation of dietary fatty acids.

Impaired essential fatty acid metabolism in latent tetany.

Because of the biochemical role of magnesium in the metabolism of polyunsaturated fatty acids, we measured the levels of polyunsaturated fatty acids in the plasma phospholipids of 40 patients with latent tetany (LT). The level of linoleic acid (18:2 n-6) was 25% higher in patients than in controls (p less than 0.001). In contrast, dihomogamma linoleic acid (20:3 n-6) was 34% lower, arachidonic acid (20:4 n-6) was 14% lower than in controls (p less than 0.01) and the ultrapolyunsaturates, 22:4 n-6 and 22:5 n-6, were reduced by 27 and 53%, respectively (p less than 0.001). Linolenic acid (18:3 n-3) was not significantly different from control levels, but its metabolite, eicosapentaenoic acid (20:5 n-3) was reduced by 43% (p less than 0.05). Since the levels of plasma phospholipid fatty acids are a reflection of hepatic metabolism, these findings suggest that patients with LT have impaired desaturation of 18:2 n-6 and possibly 18:3 n-3. The desaturase enzyme is Mg dependent, and impaired desaturation has been demonstrated in animals rendered Mg deficient. Possible consequences of this impairment in essential fatty acid (EFA) metabolism are an increase in membrane viscosity and a distortion in the availability of fatty acid precursors for prostaglandin synthesis. Either of these abnormalities may contribute to the pathogenesis of illness associated with LT.

Normocalcemic tetany and candidiasis.

We have observed a high frequency of chronic Candida albicans infection and of allergic sensitization to candida among patients with normocalcemic latent tetany (LT). Among 50 LT patients, 34% suffered from recurrent or chronic candida infection by history, 24% showed evidence of active infection and 48% demonstrated type I hypersensitivity to C. albicans extract on intradermal testing. Treatment with oral antifungal drugs and allergy desensitization to Candida produced complete relief of symptoms in 44% of the patients, with remission occurring for symptoms of depression, irritable bowel syndrome, fatigue, premenstrual tension, headache, anxiety and back pain. The complex relationship between candidiasis and Mg deficit is discussed. Patients with LT, refractory symptoms and a history of prolonged antibiotic exposure or recurrent candida infection should be considered for oral antifungal therapy and candida desensitization.

Behavioral factors and urinary tract infection.

Voiding and sexual habits of 84 female university students with a history of recurrent urinary infection were compared with those of a control group. There was one highly significant difference between the two groups: 61% of the patients but only 11% of the controls gave a history of regular voluntary deferral of micturition for periods of one hour to longer than six hours. Sexual practices among patients and controls were remarkably similar. A behavioral regimen stressing regular, complete bladder emptying was shown to be effective in preventing reinfection in the patient group. Voluntary urinary retention may play a pathogenic role in women with recurrent urinary tract infection, and its correction may play an important part in the management of urinary tract infection.

Sub-acute toxicity of xylitol in rats; absence of hepatotoxicity.

Some workers have suggested that 6 days xylitol administration to rats results in hepatic dysfunction. In our study xylitol was administered to rats by daily gastric intubation for a period of 14 days. Dose levels were 1.25, 2.5, 5 and 10 g/kg. During treatment (2, 5 and 14 days), animals were submitted to careful clinical examinations and to blood serum analysis related to hepatic functions. They were sacrificed after 2, 5, and 14 days treatment. In the 2 and 5 days treatment groups, main organs were submitted to histological study. This examination was only performed on liver in the 14 days treatment group. No evidence of hepatotoxicity was recorded. Serum levels of all parameters measured were within normal limits (including bilirubin and serum alkaline phosphatase (SAP). No anomalies were shown histologically.