[Etio-pathogenetic mechanisms of recurrences of atrial fibrillation of toxic alcoholic origin]. / Etiopatogeneticheskie mekhanizmy retsidivirovaniia fibrilliatsii predserdii alkogol'no-toksicheskogo geneza.

The following conditions in patients with alcoholic cardiac involvement predispose to recurrences of atrial fibrillation: atrial dilatation, shortening of refractory period, slowing of atrial conduction, increased vulnerability to extra stimuli, appearance of fragmented electrical activity i.e. late atrial potentials on high resolution ECG, autonomic influences on the heart, hypokalemia and hypomagnesemia.

[Predictors of ventricular tachycardia in patients with mitral prolapse]. / Prediktory vozniknoveniia zheludochkovykh takhikardii u bol'nykh s prolapsom mitral'nogo klapana.

128 patients with primary mitral prolapse and 72 healthy controls were examined using noninvasive methods. The analysis of the findings revealed predictors of electric myocardial unstability: reduced variability of cardiac rhythm, diastolic left ventricular dysfunction, late ventricular potentials and growing dispersion of the Q-T interval. Detection of mitral regurgitation correlates with development of ventricular arrhythmia.

[Factors affecting onset of ventricular arrhythmias and sudden death in patients with dilated cardiomyopathy]. / K voprosu o faktorakh, vliiaiushchikh na vozniknovenie zheludochkovykh aritmii i vnezapnoi smerti u bol'nykh s diliatatsionnoi kardiomiopatiei.

The study of 46 patients suffering from dilated cardiomyopathy has shown that both ventricular tachycardias detected at 24-h ECG monitoring and late ventricular potentials are essential predictors of sudden arrhythmic death. These predictors depend neither on severity of left ventricular systolic and diastolic dysfunction nor on severity of cardiac decompensation.

Relationship between urinary calcium and calcium intake during calcitriol administration.

The hypercalciuria that occurs when 1,25 (OH)2D3 (calcitriol) is given to humans with normal renal function depends on dietary Ca absorption and may also relate, in part, to enhanced bone resorption. To evaluate the relationship between urinary and dietary Ca during treatment with calcitriol, 12 metabolic balance studies were performed in normal volunteers ingesting a diet containing 350 mg/day of Ca, to which Ca gluconate was added. After 10 days on either 350 mg/day or 1550 mg/day of Ca, calcitriol, 0.5 microgram every 12 hr, was given. Then diet Ca was changed in successive 5-day treatment periods from 350 to 650, 950 and 1550 mg/day (group A) or from 1550 to 950, 650 and 350 mg/day (group B). On the lowest diet Ca, urinary Ca was less than Ca intake during calcitriol treatment (group A, 220 +/- 50 mg/day; group B, 247 +/- 40). As diet Ca was changed during calcitriol treatment, urinary Ca correlated with diet Ca (r = 0.60) until diet Ca reached 950 mg/day. With calcitriol, serum iPTH fell by 18 to 25% (P less than 0.01) and urinary hydroxyproline fell by 11 to 19% (P less than 0.05 to 0.01). Baseline serum levels of 1,25(OH)2D were 47 +/- 8 and 34 +/- 5 pg/ml in group A and B, respectively, and the values increased to 51 +/- 12 and 45 +/- 7.4 pg/ml during treatment with calcitriol. Serum Ca from fasted subjects was not affected by calcitriol, but the mean postabsorptive serum Ca (moon) was increased by 0.35 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of age on bone mineral regulating hormones.

The objective of this study was to determine the effect of age on the blood levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive parathyroid hormone (iPTH) in normal, healthy males and females. A total of 855 normal subjects (361 males and 494 females) were studied. The results show that for healthy males, blood concentrations of 1,25(OH)2D remained essentially constant with increasing age up to age 65, and then the concentrations decreased significantly. For healthy females, 1,25(OH)2D increased up to age 65, and then decreased at a significant rate. Serum iPTH in males increased with advancing age, but the rate of increase was greater after age 65. In females a significant increase in iPTH concentrations did not occur until after age 65. Serum creatinine increased in both males and females with advancing age.

Pharmacokinetics and biologic effects of calcitriol in normal humans.

The dose response and pharmacokinetics of orally administered calcitriol were investigated in normal humans. In one protocol, six volunteers received calcitriol 0.25 micrograms twice a day, 0.5 micrograms daily, and 0.5 micrograms twice a day, in successive weeks. Peak plasma levels of 1,25(OH)2D occurred 4 to 8 hours after ingestion of a single dose of 0.5 micrograms, with a return to baseline within 24 hours. The 8:00 AM calcitriol plasma levels were raised only when the drug was given twice daily. Urinary calcium excretion (UCa) was significantly increased from 199 +/- 19 mg/24 hr during the control period to similar levels of 302 +/- 26 mg/24 hr after 0.25 microgram twice a day and 284 +/- 31 mg/24 hr after 0.50 microgram daily. With 0.50 microgram twice a day, UCa was 417 +/- 36 mg/24 hr, a value greater than after the lower doses (p less than 0.05). In another protocol, fourteen volunteers received calcitriol 0.25 microgram, 0.5 microgram, and 1.0 microgram twice a day each for 14 days with intervening control periods of 2 weeks. A dose-related response in urinary calcium/creatinine excretion occurred. Thus, UCa (milligrams calcium per milligram creatinine) increased with calcitriol from 0.13 +/- 0.014 mg to 0.15 +/- 0.018 mg with 0.25 microgram twice a day, from 0.13 +/- 0.010 mg to 0.22 +/- 0.022 mg with 0.5 microgram twice a day, and from 0.12 +/- 0.012 mg to 0.23 +/- 0.012 mg with 1 microgram twice a day (p less than 0.05 with 0.25 microgram, p less than 0.01 with 0.5 and 1 microgram twice a day).(ABSTRACT TRUNCATED AT 250 WORDS)

The in vivo gastrointestinal absorption in rats of the intact cyclo(L-leucylglycine) dipeptide.

Unanesthetized rats with catheterized portal veins were administered, intragastrically, a saline solution of the diketopiperazine cyclo(L-leucyl-[U-14C]glycine) (cyclo(L-Leu-[14C]Gly)) at a dose of 47.9 nmol. The appearance of this cyclic dipeptide in portal vein plasma was followed chromatographically using a microcolumn of Sephadex G-25 complexed with copper. Further identification was done by thin-layer chromatography. Net absorption was evaluated by the balance method. The intestinal site of maximal absorptive capacity for cyclo(L-Leu-[14C]Gly) was also investigated. The gastric emptying rate was 98% in 15 min. After intragastric administration, cyclo(L-Leu-[14C]Gly) was absorbed (peak at 2.5 min) into the portal vein. The balance method showed that the efficiency of absorption was 94% within the first 10 min and was completed after 20 min. This compound was absorbed intact and remained unmetabolized in the portal vein of the rat and seemed to be absorbed throughout the length of the small intestine. Shortly after administration (1- to 5-min period), the greatest absorption of the diketopiperazine occurred at the level of the duodenum; however, the absorption maximum appeared to move down the gut and after 10 min the highest uptake took place in the jejunum, but never seemed to reach the ileum to a significant degree. Only negligible amounts of the cyclic dipeptide were excreted with the feces. Cyclo(L-Leu-[14C]Gly) is thus an example of a low molecular weight peptide which is rapidly and completely absorbed, after its intragastric administration at low concentration and is enzymatically stable during the process of absorption. In vitro experiments determined that this peptide apparently traverses the intestinal wall passively and does not use the carrier-mediated mechanisms for linear peptides.

Some effects of deoxycholate administration on the metabolism of cholesterol in man.

Hypercholesterolemic subjects in a metabolic ward were kept under uniform dietary conditions until constant levels of serum cholesterol were observed. Oral dosage with deoxycholate (1.5 to 3 g daily for a period of 4 to 10 weeks) resulted in a marked reduction of serum cholesterol concentration. Studies with 14C-labeled cholesterol demonstrated that deoxycholate administration decreased absorption of cholesterol from the human intestinal tract. In these subjects, the turnover rate of serum cholesterol was more rapid during therapy with deoxycholate than during control periods. Deoxycholate appeared to influence the intestinal flora as assessed indirectly by analysis of the types of neutral sterols eliminated with the feces. Decreased synthesis of cholesterol during deoxycholate administration uas demonstrated in a study with 14C-mevalonate. It is concluded that deoxycholic acid can have an important role in the regulation of cholesterol metabolism in humans.

Availability of adipose tissue tocopherol in the guinea pig.

Young guinea pigs were fed a purified diet containing vitamin E for 3 weeks and then fed the diet without vitamin E for 8 weeks. Levels of vitamin E in plasma and liver decreased to low values within a week. Depletion rates for heart and muscle were much slower, whereas the rate of loss from fat was negligible. In experiments with more mature guinea pigs and a depletion period of 4 months, the depletion rate of tocopherol from fat was also barely detectable. Both yound and mature guinea pigs developed myopathy after 8 weeks of depletion. Apparently, tocopherol in adipose tissue is not sufficiently available to maintain plasma tocopherol levels or to prevent signs of vitamin E deficiency. Even during fasting, adipose tissue tocopherol was not mobilized readily. During a 4 day fast, adipose tissue mass diminished considerably, but there was no appreciable loss of tocopherol.

Increased glucagon secretion in protein-fed rats: lack of relationship to plasma amino acids.

This investigation was designed to test the hypothesis that protein feeding stimulated glucagon secretion because amino acids liberated during protein digestion function as glucagon secretagogues. Rats were fed high-protein (HP) or control diets for 9--10 days and blood taken from the aorta or portal vein (PV) at 0800, 1300, 1700, 1900, 2100, and 2300 for determination of amino acids, glucose, insulin, and glucagon. Glucose, insulin, and glucagon of control rats showed little change. In HP rats, PV glucose rose during fasting (0800-1700) and declined during feeding (1700-0800), changes that reflected alterations of glucagon and insulin secretion. PV glucagon in HP rats that was elevated 2--4 times rose during fasting, whereas PV and arterial amino acids declined. HP feeding caused enhanced glucagon release that was associated with increased amino acids in PV and arterial plasma, especially the branched-chain group. Although these findings suggest that protein feeding promotes glucagon release because branched-chain amino acids are elevated, these amino acids are known to have little effect on alpha cell function. Thus, we conclude that protein feeding influences glucagon secretion through some mechanism other than increased blood amino acid levels.

Binding of vitamin B12--rat transcobalamin II and free vitamin B12 to plasma membranes isolated from rat liver.

When dialysed rat serum which contains a single, low molecular weight binder for vitamin B12, rat transcobalamin II (rat TC-II), was labelled in vitro with 57Co-vitamin B12 and then incubated at 30 degrees C (pH 7-5) with vesicles of highly purified plasma membranes separated from microsomal fractions of rat liver by density gradient centrifugation, the 57Co-vitamin B12-rat TC-II complex bound to high affinity sites on the vesicles via a specific (binding after correction for 'non-specific' binding in the presence of a large excess of the non-radioactive complex), saturable, and reversible interaction. The apparent affinity constant for the binding reaction was 5-5 X 10(9) M-1. Using the same incubation conditions, free vitamin B12 also bound to the vesicles of plasma membranes via a specific, saturable, but apparently irreversible interaction. Preincubation of the membranes with free vitamin B12 did not interfere with the subsequent binding of the vitamin B12-rat TC-II complex to the membranes; however, preincubation with the vitamin B12-rat TC-II complex did interfere, to some extent, with the subsequent binding of free vitamin B12. Dialysed rat serum, perhaps the free rat TC-II in the dialysed serum, also inhibited the binding of the vitamin B12-rat TC-II complex to the plasma membranes. The relationship of the binding sites identified in this report to the absorption of vitamin B12 by rat liver, and thus their physiological significance remains unknown until further work is done, perhaps using intact hepatocytes.