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M R Wills

Publications and source records attributed to M R Wills.

At least 73 records · Page 4Linked to original sources
PubMed1987

Transferrin binding of Al3+ and Fe3+.

An understanding of Al3+-induced diseases requires identification of the blood carrier of Al3+ to the tissues where Al3+ exerts a toxic action. Quantitative studies demonstrate that the protein transferrin (iron-free) is the strongest Al3+ binder in blood plasma. Under plasma conditions of pH 7.4 and [HCO3-]27 mmol/L, the successive stability constant values for Al3+ binding to transferrin are log K1 = 12.9 and log K2 = 12.3. When the concentration of total Al3+ in plasma is 1 mumol/L, the free Al3+ concentration permitted by transferrin is 10(-14.6) mol/L, less than that allowed by insoluble Al(OH)3, by Al(OH)2H2PO4, or by complexing with citrate. Thus transferrin is the ultimate carrier of Al3+ in the blood. We also used intensity changes produced by metal ion binding to determine the stability constants for Fe3+ binding to transferrin: log K1 = 22.7 and log K2 = 22.1. These constants agree closely with a revision of the reported values obtained by equilibrium dialysis. By comparison with Fe3+ binding, the Al3+ stability constants are weaker than expected; this suggests that the significantly smaller Al3+ ions cannot coordinate to all the transferrin donor atoms available to Fe3+.

Aluminum↗
PubMed1986

Trace metals and degenerative diseases of the skeleton.

Aluminum related osteodystrophy is the most important manifestation of trace metal toxicity related to degenerative diseases of the skeleton. Aluminum overload occurs in chronic renal failure patients on hemodialysis treatment and results from transfer from dialysis solutions and from oral intake of aluminum containing phosphate binding gels. Laboratory diagnosis involves serum and bone analysis and bone staining for aluminum. A challenge test with desferrioxamine also aids in the diagnosis. Electrothermal atomic absorption spectrometry is widely used for aluminum detection. Guidelines for toxic concentrations of aluminum have been established.

Aluminum↗
PubMed1986

Physiological properties of the luteinizing hormone pulse signal: impact of intensive and extended venous sampling paradigms on its characterization in healthy men and women.

The pulsatile nature of the gonadotropin signal is a critical determinant of physiological activation of the gonadal axis. Nonetheless, major uncertainties exist regarding the exact patterns of LH secretion that constitute normal physiological profiles in man. To assess possible bases for the discrepancies in the literature, we sampled blood at 5-min intervals for 24 h in eight normal men and eight normal women in the early follicular phase of the menstrual cycle. The constituent 5-, 10-, 15-, and 20-min immunoactive LH series and the consituent 6-, 12-, or 24-h sampling durations provided ranges of sampling intensities and durations for analysis of significant LH pulses. A technique for minimizing the influence of false positive immunoassay errors on peak detection was used to aid in estimating apparent true positive LH pulse frequency. Nonlinear curve fitting of the relationship between sampling intensity and apparent true positive LH pulse frequency revealed a stable pulse frequency estimate at intensive rates of venous sampling, with values of 19.5 +/- 1.9 (+/- SEM) pulses/24 h (periodicity, 73.8 +/- 6.5 min/pulse) in men and 20.6 +/- 3.6 pulses/24 h (periodicity, 70.0 +/- 10 min/pulse) in women. Further analyses indicated that sampling every 3.1 and 2.0 min for 24 h would be required to capture 90% of the LH pulses in men and women, respectively. Moreover, even with a 5-min sampling rate, the statistical counting errors of the LH pulse frequency estimates varied markedly with sampling duration; for example, in men sampled in 6-, 12-, and 24-hr sessions, the values were, respectively, 49%, 35%, and 24% of the observed pulse frequencies. Similar variations were found in women. Counting errors were 30-50% higher for conventional 20-min sampling rates than for 5-min sampling intervals. Measured interpulse intervals varied widely from 10-330 min (median, 60 min; n = 131 LH pulses) in men and from 10-340 min (median, 65 min; n = 125 LH pulses) in women. In addition, absolute LH pulse amplitudes varied from 1-28 mIU/ml (median, 4.1 mIU/ml) in men and from 1-24 mIU/ml (median, 3.6 mIU/ml) in women. These estimates were associated with a median number of points identified within each pulse of 6.0 in men and 4.0 in women. In summary, the present exhaustive sampling studies demonstrate for the first time stable estimates of physiological LH pulsations in normal men and women, and document broad ranges of normal LH pulse amplitudes and interpulse intervals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Magnesium and potassium. Inter-relationships in cardiac disorders.

Magnesium and potassium are the 2 major intracellular cations. The intracellular concentrations of these 2 ions appear to be closely correlated, but the existence of a relationship between the plasma concentrations of these ions has been controversial. A major function of potassium is to maintain the excitability of nerve and muscle tissue. Alterations in either the intracellular or extracellular potassium concentration affect membrane excitability by alterations in the resting membrane potential. The critical factor is not the actual potassium concentration in either compartment but rather the ratio of the intracellular to the extracellular concentration. The intracellular concentration of potassium is maintained against an electrochemical gradient by active transport involving an ionic pump mechanism. In this metabolically active ion-pump mechanism the inward transport of potassium is balanced by the outward transport of sodium; this active transport mechanism involves magnesium. The plasma concentration of potassium has been reported to be an important factor in the genesis of cardiac arrhythmias. The arrhythmogenic mechanisms of hypokalaemia, particularly in mild degrees, have not been clearly defined. However, evidence has begun to accumulate that magnesium deficiency may be a critical factor in the cardiac arrhythmias associated with hypokalaemia. Diuretic drugs are recognised as primary agents in the treatment of essential hypertension. In patients on antihypertensive treatment evidence has recently been reported that there is a link between the administration of diuretics and sudden death. In addition to their action on the renal tubular handling of sodium and water, diuretic drugs affect the renal tubular handling of other ions. A well-established complication of therapy with diuretic drugs is an increased urinary excretion of potassium resulting in hypokalaemia. Hypokalaemia and hypomagnesaemia can be induced by the same mechanisms and are often clinically correlated with one another. The reported incidence of hypomagnesaemia is greater than that of hypokalaemia; a significant correlation also appears to exist between the plasma concentrations of magnesium and potassium. A significant inter-relationship between the plasma concentrations of magnesium and potassium and the evidence for a critical role of magnesium in the genesis of cardiac arrhythmias would support the proposal that magnesium should be routinely measured in situations, such as diuretic therapy, that are potentially associated with hypokalaemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmias, Cardiac↗
PubMed1986

Absorption of aluminum from aceglutamide aluminum in healthy adult males.

The absorption of aluminum was studied in twelve healthy male volunteers over a period of fourteen days in a placebo-controlled, double blind study. All subjects were institutionalized during the study. Eight subjects (treated group) received ascending doses of aceglutamide aluminum (N-acetyl-L-glutamine aluminum complex) administered in multiple daily doses. The remaining four subjects (untreated group) received placebo. Systemic absorption and excretion of aluminum were evaluated by measuring aluminum concentrations in serum, urine and fecal samples. Aluminum concentrations were determined by electrothermal atomic absorption spectrometry. All serum aluminum concentrations were less than 16 micrograms/L for both groups. The mean urinary and fecal aluminum concentrations in the aluminum-treated group were significantly higher than in the untreated group during the study days the drug was administered. The total amount of aluminum (as aceglutamide aluminum) given to each treated subject during the 14 day study period as 3290 mg. The mean total fecal aluminum concentration was 3318 mg for the treated group and 269 mg for the untreated group during the study period. These findings are consistent with the view that some aluminum absorption from the gastrointestinal tract occurred following the administration of the drug. The absorbed aluminum appears to have been rapidly excreted in the urine and the feces.

Adolescent↗
PubMed1986

Methods for the estimation of serum magnesium in clinical laboratories.

A variety of methods have been reported for the quantitative analysis of magnesium in serum and other biological fluids. The methods may be classified into the following groups: magnesium ammonium phosphate; 8-hydroxyquinoline; titan yellow; dihydroxyazobenzene using fluorimetry; Schwarzenbach ethylenediaminetetraacetic acid; atomic emission spectrophotometry; atomic absorption spectrophotometry; ion chromatography, and carboxanilide, calmagite and related dye methods. These methods are reviewed with specific emphasis on the limitations for their use in clinical laboratories.

Azo Compounds↗
PubMed1985

Serum and lymphocyte, aluminum and nickel in chronic renal failure.

In the past decade, aluminum has been recognized as a toxic metal in patients with chronic renal failure. It is, however, possible that other trace metals, such as nickel, may also have toxic actions in these patients. The plasma concentration of a metal, such as aluminum or nickel, may not provide a valid index of either tissue content or total body burden. In the study reported here, the aluminum and nickel content of lymphocytes was measured and compared with plasma concentrations in normal controls and patients with chronic renal failure. The findings suggest that lymphocytes may be of value as a nucleated 'tissue' for the assessment of trace metal status.

Adult↗
PubMed1985

Aluminium toxicity in chronic renal insufficiency.

Aluminium is a ubiquitous element in the environment and has been demonstrated to be toxic, especially in individuals with impaired renal function. Not much is known about the biochemistry of aluminium and the mechanisms of its toxic effects. Most of the interest in aluminium has been in the clinical setting of the haemodialysis unit. Here aluminium toxicity occurs due to contamination of dialysis solutions, and treatment of the patients with aluminium-containing phosphate binding gels. Aluminium has been shown to be the major contributor to the dialysis encephalopathy syndrome and an osteomalacic component of dialysis osteodystrophy. Other clinical disturbances associated with aluminium toxicity are a microcytic anaemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and haemodialysis. Aluminium is readily transferred from the dialysate to the patient's bloodstream during haemodialysis. Once transferred, the aluminium is tightly bound to non-dialysable plasma constituents. Very low concentrations of dialysate aluminium in the range of 10-15 micrograms/l are recommended to guard against toxic effects. Very few studies have been directed towards the separation of the various plasma species which bind aluminium. Gel filtration chromatography has been used to identify five major fractions, one of which is of low molecular weight and the others appear to be protein-aluminium complexes. Recommendations on aluminium monitoring have been published and provide 'safe' and toxic concentrations. Also, the frequency of monitoring has been addressed. Major problems exist with the analytical methods for measuring aluminium which result from inaccurate techniques and contamination difficulties. The most widely used analytical technique is electrothermal atomic absorption spectrometry which can provide reliable measurements in the hands of a careful analyst.

Aluminum↗
PubMed1985

Water content of aluminum, dialysis dementia, and osteomalacia.

In the presence of normal renal function, a high concentration of aluminum in drinking water has been implicated as a factor in the etiology of a neurological syndrome in one specific geographical area. The role of aluminum as a toxic agent in other neurological disorders, where renal function is normal, is controversial. Aluminum is absorbed from the gastrointestinal tract and is normally excreted by the kidneys in the urine. In patients with chronic renal failure, aluminum appears to be of proven toxicological importance. In these patients the accumulation of aluminum in tissues causes an encephalopathy (dialysis encephalopathy or dialysis dementia), a specific form of metabolic bone disease (osteomalacic dialysis osteodystrophy), and an anemia and also plays an etiological role in some of the other complications associated with end-stage chronic renal disease. A failure in the normal renal excretory mechanism accounts for the tissue accumulation in chronic renal failure. The majority of chronic renal failure patients who develop aluminum toxicity are on long-term treatment with either hemo- or peritoneal dialysis; some patients develop toxicity who are only on treatment with aluminum-containing phosphate-binding agents. Aluminum in the dialysate appears to be the major source of the metal in chronic renal failure patients who develop aluminum toxicity. The aluminum content of the dialysate depends primarily on the content of the water with which it is prepared; there may be some contribution from the chemicals used in the concentrate which is added to the water. Some domestic tap-water supplies contain aluminum in high concentration, either naturally or because aluminum has been added as a flocculant in the purification process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1985

Uremic toxins, and their effect on intermediary metabolism.

In the late stages of chronic renal damage the functional mass of the kidney is reduced and there is progression to renal insufficiency, usually called uremia, in which all aspects of renal function are affected. The complexity of the biochemical aspects of the syndrome of uremia is a manifestation of the wide variety and nature of the individual disorders that contribute to the pathogenesis of the final clinical syndrome. One major feature is the retention of metabolic end products and their effects, as toxins, on intermediary metabolism. The retained end products, working singly or in combination, probably affect metabolic pathways by some modification of enzymic reactions. They act at the cell membrane level. Although "middle molecules" have been incriminated as uremic toxins, recent attention has also focused on trace elements--especially aluminum, which has been implicated in the pathogenesis of two major disorders, osteomalacic dialysis osteodystrophy and dialysis encephalopathy.

Aluminum↗
PubMed1985

Evaluation of equilibrium gel filtration chromatography for the study of protein binding of aluminum in normal and uremic sera.

Normal and uremic serum samples were chromatographed on a gel filtration column and fractions were analyzed for protein and aluminum content. Whereas much of the aluminum in the serum samples eluted with protein, a significant fraction appeared to be associated with low molecular weight species. Analysis of column fractions for aluminum binding by a competitive binding assay indicated no aluminum-binding serum constituents in these later eluting fractions. Uremic serum appeared, however, to contain aluminum-binding constituents of a lower molecular weight than in normal serum.

Aluminum↗
PubMed1984

Quantitative study of aluminum binding to human serum albumin and transferrin by a chelex competitive binding assay.

Binding of aluminum to human serum albumin and transferrin was investigated using a competitive binding assay incorporating a cation exchange resin, chelex. Both albumin and transferrin were found to produce linear Scatchard plots of aluminum binding data over the aluminum and protein concentration ranges found in humans. Binding constants measured for albumin and transferrin were 1.96 and 0.515 microM, respectively.

Aluminum↗
PubMed1984

Electrothermal atomic absorption spectrometric determination of aluminum in serum with a new technique for protein precipitation.

We have studied the electrothermal atomic absorption measurement of aluminum in serum samples by direct analysis with standard additions and the use of a matrix modifier. We have also measured aluminum by analysis of the supernate after pretreatment of serum with concentrated nitric acid to precipitate proteins, and have compared the results obtained by these two techniques. Both appear to eliminate interferences arising from the serum matrix. We quantified the aluminum by utilizing a stabilized temperature (L'vov) platform. Within-run precision (CV) for the standard-additions method was 16.6% (means = 6.5 micrograms/L) and 6.0% (means = 86.8 micrograms/L) and for the protein precipitation method was 10.1% (means = 10.9 micrograms/L) and 4.2% (means = 88.5 micrograms/L). Linearity of the standard curve extended from 0 to 120 micrograms/L for the standard-additions method and from 0 to 100 micrograms/L for the protein precipitation method. Samples from 38 patients were analyzed by both techniques, and linear regression analysis yielded the equation y (protein precipitation) = 1.02 X (standard additions) + 2.04.

Aluminum↗