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[Ascorbic, keto and hydroxy acid metabolism in the cell nuclei of certain tumors].

The authors report the results of studies on the content of ascorbic acid, pyruvic acid and the activity of malate dehydrogenase decarboxylizing (MDHD) in cell nuclei of uterine fibromyoma, glandular hyperplasia of the endometrium with epithelial proliferation, common ovarian cyst and solid cancer. It was shown that due to the glycolysis inhibited respiration an oxidated form of ascorbic acid is absent in every case, whereas the MDHD activity is not manifested. The amount of a reduced form of ascorbic and pyruvic acid in benign tumors is at the control level, but in malignant growth these indices are markedly increased.

Ascorbic Acid↗

[Fixed acids during the traditional cesarean section in cows].

The values of lactic acid, pyruvic acid and L/P index were studied in cows at the traditional Caesarean section. The values of the mentioned metabolites are presented in dependence on the intensity and length of parturient activity that are affected by the anesthesia applied during surgical procedures. An increase of the level of lactic acid was hindered by the anesthesia at the protracted parturient activity. An unequal drop of the level of lactic acid resulted from the interrupted intensive parturient activity and lowered labor of the organisms due to anesthesia during the surgical procedure. The levels of pyruvic acid increase after the anesthetic applied, but already during the surgical procedure a drop of their levels occurs that continues, with certain fluctuations, for 48 hours after the fetus extraction. The L/P index is relevant to the levels of fixed acids that reflect the labor of the organism at the protracted parturient activity and under an oxygen deficit. The increased L/P index after the application of the anesthetic decreases for three hours after the surgical procedure and later on, it maintains approximately the same level.

Animals↗

[Changes of lactic and pyramic acid levels and of the L/P index in cows and calves during parturition].

The levels of lactic acid, pyruvic acid and L/P index were studied during parturition in cows and calves. The results demonstrate various values of the metabolites studied in dependence on the length of parturient activity and on the way of finishing the parturition. The level of lactic acid increases with protracted parturient activity and that of puruvic acid decreases. Anesthesia applied at the traditional caesarean section hinders the course of fixed acids, which is reflected in the values of the L/P index. An excessive accumulation of fixed acids in mother's organism at the protracted parturition unfavorably influences the metabolism of fetus by means of the fetoplacental bed. Anesthesia does not affect the levels of the metabolites studied in calves. The values of the L/P index are in the same proportion as the levels of lactic and pyruvic acids are.

Animals↗

[Suspected pyruvate carboxylase deficiency in 4 children with Leigh disease].

Clinical observations and results of investigations of pyruvic acid metabolism are reported in 4 children in whom subacute necrotizing encephalomyelopathy of Leigh was diagnosed intravitally. Attention is called to the similarity of the clinical manifestations with its onset in the first year of life, deficient body weight and growth, progressing neurological disturbances (weakening of muscle power, tremor, ataxia, nystagmus), course with periods of exacerbations, tachypnoea, skin changes (hirsutism, telangiectasia, perspiration), death at the age of 2-3 years. The biochemical changes in all children included raised serum levels of lactic acid, pyruvic acid and alanine, and acid-base equilibrium disturbances with metabolic acidosis (relatively balanced respiratory alkalosis). The results of the test of intravenous loading with glucose and alanine carried out in all children indicated indirectly reduced activity of pyruvate carboxylase. In one child histological examination of the brain carried out postmortem confirmed the diagnosis of Leigh's disease.

Brain Diseases, Metabolic↗

[Clinical trial of coenzyme A in hepatopathies].

Coenzyme A (900 L.U. i.v.) was administered for 20 days in 18 cases of viral hepatitis, 2 of chronic ethylic hepatosis, and 5 of ascitic portal cirrhosis. Blood lactic acid, pyruvic acid, serum transaminase and beta/alpha lipoprotein ratio were determined. BSF and colloidal serolability tests were also carried out. The benefits of coenzyme A treatment were particularly indicated by the significant changes noted in lactic and pyruvic acid values.

Adolescent↗

Study of factors affecting binding of zinc with albumin at physiological zinc concentrations.

Albumin has very high affinity for many organic and inorganic compounds that may influence albumin bound Zn (ABZn). To get insight of these molecular interactions, the effect of riboflavin, nicotinic acid, thiamine, folic acid, pyruvic acid and glucose on ABZn were studied. The ABZn was separated from the unbound zinc using equilibrium dialysis and estimated using atomic absorption spectrometer. At therapeutic zinc concentrations, folic acid and thiamine significantly enhanced the ABZn (p < 0.010), while nicotinic acid inhibited zinc binding to albumin. Folic acid was found to enhance the ABZn also at lower zinc concentrations representing physiological levels of plasma zinc (138-150 micromoles) (p < 0.05).

Analysis of Variance↗

Nutritional efficiency of succinic acid and glutamic acid dimethyl esters in colon carcinoma cells.

The dimethyl esters of succinic acid (SAD) and glutamic acid (GME) were found to be efficiently metabolized in colon carcinoma cells of the Caco-2 line. The rate of [1,4-14C]SAD and [2,3-14C]SAD conversion to radioactive acidic metabolites, CO2, amino acids, pyruvic acid, and lactic acid suggested that the catabolism of the ester-derived succinic acid occurred mainly through the sequence of reactions catalyzed by succinate dehydrogenase, fumarase, and the malic enzyme. This coincided with a marked sparing action of SAD on the utilization of D-[2-(3)H]glucose and D-[5-(3)H]glucose and generation of 14C-labeled acid metabolites, CO2, and lactic acid from D-[U-14C]glucose by the enterocytes. Likewise, the conversion of [U-14C]GME to 14C-labeled amino acids, its oxidation compared with that of [1-(14)C]GME, and the production of NH4+ in the absence or presence of GME indicated efficient catabolism of the latter ester. Like SAD, GME decreased the utilization of D-[5-(3)H]glucose and generation of 14C-labeled acidic metabolites, pyruvate, and CO2 from D-[6-(14)C]glucose, while increasing the generation of 14C-labeled amino acids from the labeled hexose. The oxidation of D-[6-(14)C]glucose was even more severely inhibited by GME. In normal rat intestinal cells, SAM, SAD, and GME also exerted a marked sparing action on D-[U-14C]glucose oxidation. The present findings suggest, therefore, that these esters could possibly be used to sustain ATP generation in intestinal cells.

Adenosine Triphosphate↗

Systemic effects and skin injury after experimental dermal exposure to monochloroacetic acid.

There have been many fatal occupational accidents of skin exposure to monochloroacetic acid (MCA). However, there have been no reports of dermatological findings and the lethal consequences have not yet been demonstrated. Therefore, harmful local and systemic effects were investigated after dermal exposure to MCA. A 0.5 mL aliquot of MCA solution (40% w/w) was applied to the abdominal skin of ten 10-week-old male SD rats under anesthesia. The exposure area (25 x 25 mm2) was 1.6% of the total surface area. The dose of MCA per area was 34.1 mg/cm2. Saline was similarly administered to 10 control rats. Histopathological findings after 10 min were observed by light microscopy. Blood samples were collected by exsanguinations from the carotid arteries after 4 h. Skin samples were collected 10 min after the initial exposure. Histological findings showed severe degeneration of collagen bundles in the epidermis and subcutaneous tissues. P(CO2), HCO(3)-, TCO2, BE and glucose levels were decreased in the MCA group. AST, m-AST, ALT, BUN, Cr, NH3, lactic acid, pyruvic acid, RBC, Hb, Hct, total protein and albumin were increased in the MCA group. The burn was determined to be a third-degree burn on the basis of the histopathological findings. The severe toxicity was probably a consequence of the rapid permeability. Biochemical parameters were a consequence of hepatocellular injuries, renal dysfunction, dysglyconeogenesis and dysfunction of ammonia metabolism. MCA reportedly enters the TCA cycle and inhibits aconitase. MCA metabolites also inhibit pyruvate carboxylase in the gluconeogenesis pathway. Therefore, the important serum biochemical abnormalities such as hypoglycemia and lactic acidosis should be monitored to find the acute systemic disorders.

Accidents, Occupational↗

Increased serum concentrations of lactic, pyruvic and uric acid and bilibubin after postoperative xylitol infusion.

Xylitol has been suggested as a more advantageous calory source for intravenous administration than glucose in certain clinical situation, but the general suitability of intravenous xylitol infusion has not been confirmed. Thirty-middle-aged women were infused with 100 g of xylitol as postoperative fluid therapy after gynaecological laparotomy and general anaesthesia. Another 10 women received 50 g of glucose in a similar manner and served as a reference group. Infusion of xylitol both at the rate of 0.25 g/kg/h (1000 ml 10% xylitol in approx. 8 h) and 0.5 g/kg/h (1000 ml 10% xylitol in approx. 4 h) caused a distinct increase in the serum concentrations of lactic acid, pyruvic acid, and uric acid; such an increase was not seen with glucose infusion. The faster infusion of xylitol also distinctly increased serum bilirubin concentrations. Because of the possibility of lactic acidosis and urate deposits in kidneys, infusion of 100 g or more of xylitol at a rate of 0.25 g/kg/h or faster is not safe for postoperative fluid therapy in routine clinical work.

Anesthesia, General↗

FACTORS THAT INFLUENCE TOXIGENICITY OF PSEUDOMONAS AERUGINOSA.

Liu, Pinghui V. (University of Louisville, Louisville, Ky.). Factors that influence toxigenicity of Pseudomonas aeruginosa. J. Bacteriol. 88:1421-1427. 1964.-Hemolysin, lecithinase, and protease of Pseudomonas aeruginosa were produced with cellophane-covered plates and completely synthetic agar of simple composition containing alpha-alanine, aspartic acid, glutamic acid, glucose, and salts. The most critical factor in the production of these extracellular toxins appeared to be the concentration of phosphate, which had to be in the range of 0.003% for the lecithinase, 0.005 to 0.01% for the hemolysin, and 0.01 to 0.2% for the protease. alpha-Alanine and glutamic acid favored the production of the hemolysin and lecithinase, and aspartic acid supported the production of protease. The role of glucose in the production of these extracellular toxins appeared to be more important than just an energy source. It is likely that products of anaerobic metabolism of glucose are needed in the production of these toxins. In the absence of glucose, the production of protease was enhanced by lactic acid, pyruvic acid, or alpha-ketoglutaric acid. Possible implications of these findings in the pathogenesis of P. aeruginosa are discussed.

Alanine↗

[Mitochondrial encephalomyopathy (focal cytochrome c oxidase deficiency) with transient episodes of muscle weakness and elevation of serum creatine kinase activity].

A 17-year-old boy who had mitochondrial encephalomyopathy with focal deficiency of cytochrome c oxidase (CCO) activity is described. He experienced 3 episodes of muscle weakness, fatigability, nausea, vomiting and concomitant increase of serum creatine kinase activity, at the age of 13, 15 and 17 years. During interval there was no muscle weakness and the serum creatine kinase activity was within normal range. Increased levels of lactic acid and pyruvic acid were observed in the blood and cerebrospinal fluid. After an aerobic exercise test, lactic acid and pyruvic acid in the blood increased to an abnormally high level, and the arterial blood became acidic (pH 7.297). On EEG, occasional intermittent irregular theta activities were observed in the anterior region, but there were no abnormalities on CT and MRI in the central nervous system. In the biopsied muscle, ragged-red fibers comprised 20% on modified Gomori-trichrome staining and a number of fibers with no CCO activity were scattered throughout. The CCO activity in the mitochondria isolated from the biopsied muscle was reduced to 49.2 nmol/min/mg protein (normal range 144.7-355.8), while other mitochondrial enzyme activities in the electron transport system were normal. From these data, the patient was considered to have a unique form of mitochondrial encephalomyopathy. By the administration of a large amount of coenzyme Q10, episodes of muscle weakness and nausea, and an increase of lactic acid and pyruvic acid in the blood after aerobic exercise test were no longer observed.

Adolescent↗

Growth of obligate autotrophic bacteria on glucose in a continuous flow-through apparatus.

Nitrosomonas europaea, Nitrobacter agilis, Thiobacillus denitrificans, T. neapolitanus, and T. thioparus (all obligate autotrophic bacteria) have been grown in dialysis culture, on glucose salts media, in the absence of their specific inorganic energy source. Metabolic products for N. agilis grown on nitrite salts medium were identified as keto acids. Pyruvic acid inhibited this organism at 5 x 10(-5)m. Keto acids were not inhibitory for the thiobacilli grown on thiosulfate medium. However, when T. denitrificans was grown on glucose with dialysis, addition of 5 x 10(-4)m pyruvate inhibited growth. Thus, it appears pyruvate may be inhibitory for other autotrophs, as has been reported for T. thiooxidans.

Ammonia↗

Penitrem A intoxication of calves: blood chemical and pathologic changes.

An isolate of Penicillium puberulum, obtained from moldy silage, was found to produce a tremorgenic mycotoxin, penitrem A. Dried ground mycelium of this isolate was administered orally to calves either in increasing daily doses or in a single dose that equalled the amount given over a 3-day period in the increasing daily-dose schedule. Signs of intoxication included tremor, ataxia, muscular rigidity, and convulsive episodes. Marked increases in plasma concentrations of lactic acid, pyruvic acid, glucose, and creatine phosphokinase activity were found coincident with the development of severe tremor. The only gross or microscopic change observed in tissues of intoxicated animals was an accumulation of fat in the liver. Changes in the various plasma constituents were interpreted as a secondary effect of the intoxication.

Administration, Oral↗

[Effect of combinations of apressin, obsidan, diprazin, adenosine, NAD and nicotinamide on the resistance of rats to hypoxia and on carbohydrate metabolic indices].

As evidenced from experiments on rats, a combined application of apressin with obsidan and diprazine, and also of adenozine with nicotine-amidadenine-dinucleotide (NAD), as well as of adeozine with nicotine amide potentiates the protective effect of these substances in hypobaric hypoxia, increases the resistance of the animals to cerebral ischemia, brings down the excess lactate level and raises the redoz potential of the system lactic-acid-pyruvic acid in the brain of rats exposed to the effects of rarefied atmosphere.

Adenosine↗

Respiratory function of blood of the avians.

Individual blood samples were collected from wing veins of eight adult pigeons, two adult chickens and four adult geese and were analyzed for oxygen dissociation curves by hemo-scan, an instrument measuring PO2 and O2 saturation simultaneously. The findings agree with the common belief that avian blood in general has a low affinity for oxygen. Blood pH, PCO2, concentration of 2,3-DPG, lactic acid, pyruvic acid, red blood cell, hemoglobin and hematocrit were also determined, the related parameters have been calculated. Normal values of those variables were reported and the possible effects of some of those parameters on oxygen affinity are postulated.

Animals↗

[Circadian variations of the effects of ethanol and of blood ethanol values in the healthy adult man. Chronopharmacological study].

Six healthy young men (22 to 26 years) who had fasted for 12 hours volunteered for this study (subject synchronization: diurnal activity from 07(00) to midnight and nocturnal rest). A set dose of ethanol (0.67 g/kg body weight) was ingested at the fixed (and random) hours of 07(00), 11(00), 19(00) and 23(00), with a week between tests. A set of physiological variables: psychological tests (selft-rating of mood, of physical vigor and of ebriety, tempo, random number addition test); physical variables (heart rate, systolic and diastolic blood pressure, peak expiratory flow, oral temperature and grip strength); blood variables (plasma ethanol, cortisol, lactic acid, pyruvic acid, glucose and erythrocyte K+) and urinary variables (volume, epinephrine, nor-epinephrine and 5-HIAA) were documented at least at 4 hourly intervals and set times. The cosinor method was used for chronobiological statistical analyses. The parameters characterizing the ethanol pharmacokinetics (chronopharmacokinetics) demonstrated a circadian rhythm (p less than 0.05): e. g. the peak height of ethanolemia is greater when ethanol is ingested at 07(00) than at other times. Also a circadian rhythm in biosystems susceptibility can be demonstrated (p less than 0.05) (chronesthesy) with a peak time not necessarily corresponding either to that of ethanolemia or to that of other variables. The overall circadian changes in ethanol effects (chronergy) can be viewed as a combination of both ethanol chronesthesy and chronokinetics.

Adult↗

The effect of dietary autoxidized oils on immunocompetent cells in mice.

Effects of dietary autoxidized oil on immunocompetent cells, such as splenocytes and thymocytes, were studied in mice. When the autoxidized methyl linoleate was administered orally to male C57BL/6 mice in a single dose, the DNA synthesis of thymocytes was remarkably depressed 1 day after the treatment, and then the mitogenic response to concanavalin A of splenocytes was increased 3 days after the dose. With long-term (90 days) feeding of slightly autoxidized soybean oil (with a peroxide value of 150 mequiv/kg) in mice, the DNA synthesis of thymocytes was depressed and the mitogenic response to concanavalin A of splenocytes was increased. No effect was observed on plasma glutamic acid-oxaloacetic acid transaminase and glutamic acid-pyruvic acid transaminase levels, nor on liver thiobarbituric acid reactants due to the dose of autoxidized soybean oil. These findings indicate that oral intake of autoxidized oil affects immunocompetent cells and causes depression of the DNA synthesis of thymocytes in mice.

Animals↗

Mechanism of valproic acid uptake by isolated rat brain microvessels.

In an effort to characterize putative transport systems of valproic acid (VPA) at the blood-brain barrier, the effects of various substrates and inhibitors of known anion transporters on the equilibrium vessel-to-medium concentration (vessel/medium) ratio of VPA were investigated using isolated rat brain microvessels. The equilibrium vessel/medium ratio of VPA was decreased by the presence of high millimolar concentration of unlabeled VPA, indicating that a saturable transport system was involved in VPA transport from medium to microvessels. Short-chain monocarboxylates such as propionic acid, pyruvic acid, and L-lactic acid did not alter the vessel/medium ratio, whereas medium-chain fatty acids and unsaturated metabolites of VPA significantly inhibited the net transport of VPA. Dicarboxylates, tricarboxylate, and p-aminohippuric acid did not affect VPA accumulation in the brain microvessels. Several anionic drugs including salicylic acid, penicillin G, cefazolin, and probenecid significantly reduced the vessel/medium ratio of VPA. In addition, disulfonate inhibitors of inorganic anion exchangers, SH-group modifying reagent, and metabolic inhibitor showed remarkable inhibitory effects on the net transport of VPA between brain microvessels and medium. These results suggest that VPA may be actively transported through the antiluminal membrane via a carrier-mediated system shared by other anionic drugs.

Animals↗