Plasma homocysteine, a well-recognized risk factor for cardiovascular disease, is elevated in uremic patients on hemodialysis. The authors have recently demonstrated that one consequence is the ...reduction in red cell membrane protein methylation levels, caused by a rise of intracellular adenosylhomocysteine, a potent inhibitor of methyltransferases. Protein methylation is involved in a repair mechanism of damaged membrane proteins, and an impairment in methylation leads to the accumulation of altered proteins. Therapy with folates, cofactors in the transformation of homocysteine to methionine, is effective in lowering plasma homocysteine. This article details a study on the metabolic effects of oral methyltetrahydrofolate, the active form of folic acid, on 14 uremic hemodialysis patients. Two months of therapy led to a significant reduction of plasma homocysteine levels, with a proportional response to pre-folate levels. In five of 13 patients with homocysteine levels above 20 microM, plasma homocysteine level was reduced to less than 15 microM. After treatment, levels of adenosylmethionine, the methyl donor in transmethylations, had significantly increased; levels of adenosylhomocysteine had increased to a smaller extent. Therefore, the ratio between the two compounds, an excellent indicator of the presence and the degree of methylation inhibition, was significantly ameliorated. Methionine plasma levels increased after treatment in all patients and were correlated with posttreatment adenosylmethionine levels. It was concluded that treatment with methyltetrahydrofolate brings the plasma homocysteine concentration back to an "acceptable" level, and the metabolic consequences are in the direction of an increase in the normal flow of transmethylations, as monitored by an increase in the adenosylmethionine/adenosylhomocysteine ratio.
Salt has influenced human nutrition, health, politics, taxation, economy, freight, transport, and commerce throughout the ages. All human activities have been influenced by salt including economy, ...religious beliefs and practices, art, literature, psychoanalysis, superstitions, and exorcism. Salt is recognized as a symbol for friendship, hospitality, chastity, alliance, table fellowship, fidelity, fertility, blessing, curse and endurance, etc. The Bible is the first book of salt and contains no fewer than 24 references to this substance. In the Gospels the parable of salt is a central one. Many many church fathers have written on salt a substance, which up to 1969 was a relevant element in the rite of Baptism. This paper reviews the importance of common salt for human life, and by drawing from various scientific and literary sources makes a special discussion of its various symbolisms.
Mechanism of erythrocyte accumulation of methylation inhibitor S-adenosylhomocysteine in uremia. We have recently demonstrated that methyl esterification of erythrocyte membrane proteins, a reaction ...involved in recognition and repair of specifically damaged proteins, is impaired in uremia. This is accompanied by a significant increase in intracellular S-adenosylhomocysteine (AdoHcy), a potent inhibitor of methyltransferases. AdoHcy accumulation is normally prevented by its enzymatic hydrolysis to homocysteine (Hey) and adenosine, a reversible reaction catalyzed by AdoHcy hydrolase. To assess the contribution that Hey offers in the elevation of AdoHcy, we measured plasma and red blood cell Hey, AdoHcy, adenosine, and S-adenosylmethionine (AdoMet) intracellular concentrations, as well as RBC AdoHcy hydrolase specific activity, in standard hemodialysis patients and normal subjects. Plasma and red blood cell Hey levels are significantly higher in the dialysis group, and are positively correlated to AdoHcy levels. Adenosine and AdoMet levels, and AdoHcy hydrolase specific activity are not significantly different between the two groups. The enzymatic formation of labeled AdoHcy from Hey and tracer adenosine appears to be significantly increased, in vitro, in erythrocytes from both control and uremic patients, when 50 µM Hey (concentration comparable to plasma levels actually found in vivo in uremic patients) is added to the incubation medium. When erythrocytes from uremic patients are incubated in vitro in absence of Hey, a significant reduction of intracellular AdoHcy is observed with time compared to identical samples incubated in presence of 50 µM Hey, with a T1/2 of approximately 270 minutes. The results allow us to conclude that plasma and red cell Hey levels actually found in uremia can be effectively responsible for the intracellular accumulation of the toxic compound AdoHcy.
The enzyme protein carboxyl methyltransferase type II has been recently shown to play a crucial role in the repair of damaged proteins. S-adenosylmethionine (AdoMet) is the methyl donor of the ...reaction, and its demethylated product, S-adenosylhomocysteine (AdoHcy), is the natural inhibitor of this reaction, as well as of most AdoMet-dependent methylations. We examined erythrocyte membrane protein methyl esterification in chronic renal failure (CRF) patients on conservative treatment or hemodialyzed to detect possible alterations of the methylation pattern, in a condition where a state of disrupted red blood cell function is present. We observed a significant reduction in membrane protein methyl esterification in both groups, compared to control. The decrease was particularly evident for cytoskeletal component ankyrin, which is known to be involved in membrane stability and integrity. Moreover, we observed a severalfold rise in AdoHcy levels, while AdoMet concentration was comparable to that detected in the control, resulting in a lower AdoMet/AdoHcy ratio (P < 0.001). Our findings show an impairment of this posttranslational modification of proteins, associated with high AdoHcy intracellular concentration in CRF. The data are consistent with the notion that, in CRF, structural damages accumulate in erythrocyte membrane proteins, and are not adequately repaired.
Relation of urinary albumin excretion to coronary heart disease and low renal function: Role of blood pressure.
Previous studies report that urinary albumin excretion is associated with coronary ...heart disease (CHD). The present epidemiologic study investigated if (1) blood pressure status affects the association of urinary albumin excretion with CHD; and (2) urinary albumin excretion is associated with low renal function also.
The cross-sectional association was analyzed of overnight urinary albumin excretion with prevalence of CHD (myocardial infarction and/or ischemia as defined by standard electrocardiogram) and low renal function (overnight creatinine clearance <60mL/min) in a population sample of 1632 men and women with ages 45 to 64years. Hypertension, hypercholesterolemia, smoking habit, and diabetes mellitus were included in analyses.
CHD prevalence was in the whole sample 8.2% (N = 134), in the hypertensive subgroup 11.9% (N = 79), and in the nonhypertensive subgroup 5.7% (N = 55). For the association between urinary albumin excretion (logarithm-transformed due to skewed distribution) and CHD, the multivariate logistic coefficient with 95% CI was significant in the whole sample (+0.79, 95% CI =+0.32/+1.26, P < 0.001) and in the hypertensive subgroup (+0.97, 95% CI =+0.70/+1.24, P < 0.001), not in the nonhypertensive subgroup (-0.06, 95% CI =-0.80/+0.68, P = 0.997). Prevalence of low creatinine clearance was in the whole sample 4.0% (N = 66), in the hypertensive subgroup 4.8% (N = 32), and in the nonhypertensive subgroup 3.5% (N = 34). The logistic coefficient between urinary albumin excretion and low creatinine clearance was borderline significant in the whole sample (+0.56, 95% CI =-0.02/+1.14, P = 0.090), significant in the hypertensive subgroup (+0.73, 95% CI =+0.04/+1.42, P = 0.044), not significant in the nonhypertensive subgroup (-0.07, 95% CI =-1.25/+1.10, P = 0.913).
Results support the use of urinary albumin excretion as marker of CHD and slightly reduced renal function in hypertensives.
To investigate indices of calcium (Ca) homeostasis in celiac disease (CD).
Urinary Ca excretion rate, intestinal absorption of strontium (Sr) (used as index of intestinal Ca absorption), and other ...variables related to these end points were measured in newly diagnosed, untreated adult patients (n = 32) with overt and subclinical CD and compared with those of healthy controls (n = 27). Subclinical CD was defined by the absence of diarrhea (> or = 3 bowel movements/24 h), steatorrhea (fecal fat excretion > 6 g/24 h), and low body mass index (weight/height, kg/m2 < 21).
Compared with controls, untreated celiac patients had 2 x lower Ca excretion (p < 0.0001) in 24-h and overnight urine (fed condition) but normal Ca excretion in urine samples collected under fasting (2-h) condition; the increase in urinary Ca excretion from fast to fed condition was 4 x lower in untreated celiac patients (p < 0.0001). Patients with overt and subclinical CD did not have significantly different urinary Ca excretion rates. Sr absorption rate was 45% lower in untreated patients than controls (p < 0.0001). Patients with overt and subclinical CD did not have significantly different Sr absorption rates. Sr absorption rate (r = 0.576, p < 0.0001) related to the increase in urinary Ca excretion from fast to fed condition. In celiac patients, 24-h urinary Ca excretion increased by 52% (p < 0.0001) over baseline after 6 months of gluten-free diet, and urinary Ca excretion under fasting condition did not significantly change.
Overt and subclinical CD is associated with low urinary Ca excretion under fed condition, which relates to low intestinal absorption.
A pupil and then the successor of Vesalius to the Chair of Anatomy and Surgery at the University of Padua, Matteo Realdo Colombo (1516-1559) was equally consumed by the flame of scientific inquiry ...and recognition. His sole contribution to the literature, De Re Anatomica, was published after his death in 1559. In it, he correctly describes the position of the right kidney as lower than that of the left and provides the best description of the pulmonary circulation before that of William Harvey, who in his text duly acknowledged Colombo's contributions. In the concluding chapter, he establishes the beginnings of morbid anatomy in describing diseased organs. De Re Anatomica was widely used as a textbook of anatomy, being translated into English in 1578 and German in 1609. He came to be sufficiently well known to become physician to the Vatican. One of his best known patients was Michelangelo, with whom he vainly tried to collaborate in illustrating De Re Anatomica. A regrettable eventuality, which could have reversed the fortunes of Vesalius and Colombo in the annals of the history of medicine.
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