The glutamine paradox in a neonate with propionic acidaemia and severe hyperammonaemia.
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Amino Acid Metabolism, Inborn Errors↗
Biomedical subjects
A Mazur
Publications and source records attributed to A Mazur.
Compartmental analysis of magnesium kinetics in Mg-sufficient and Mg-deficient rats.
In this study, we determined magnesium kinetic values in normal rats using stable-isotope techniques. Additionally, we calculated the mass of the exchangeable pools of Mg in Mg-deficient rats to determine whether it can be used as a marker of Mg status. Rats were fed either a control diet (1,000 mg Mg/kg) or a Mg-deficient diet (60 mg Mg/kg). After 2 weeks on the experimental diets, each rat received an intravenous injection of 26Mg. The plasma Mg disappearance curve over the next 7 days was used to measure the mass and fractional transport rate of 3 rapidly exchanging Mg metabolic pools. In control rats, the mass of pool 1 (1.37 mg) was half that of pool 2 (2.46 mg), and pool 3 (47.7 mg) accounted for greater than 90% of exchangeable Mg. In Mg-deficient rats, we observed a significant decrease in the size of the 3 exchangeable pools of Mg (0.36, 0.72, and 20.2 mg, respectively) relative to the control rats. Furthermore, the fractional transport rate of Mg from pool 1 to pool 3 in Mg-deficient rats was 3 times the rate in the control rats, and the rate of irreversible loss from pool 1 was lower in Mg-deficient rats. In summary, this study allows us to establish Mg kinetic data in Mg-sufficient and Mg-deficient rats. The present experiment supports the conclusion that the isotopic test identifies animals with severe Mg deficiency.
Animals↗
Long-term consumption of red wine does not modify intestinal absorption or status of zinc and copper in rats.
Red wines contain many components such as polyphenols and ethanol that may influence mineral absorption. We report on studies in a rat model that were designed to investigate the extent to which short- and long-term intake of red wine or ethanol may influence (67)Zn and (65)Cu absorption in rats. Rats (n = 96) were divided into three groups, a control group that received demineralized water, a group that received red wine diluted with water (v/v) and an ethanol group that received 6% ethanol. Half of each group was used for the short-term study; the others were used for the long-term study. After 3 d (short-term study) or 28 d (long-term study) of beverage consumption, the rats were gavaged with 2 mL of solution containing 2027 nmol (67)Zn and 902 nmol (65)Cu. Subsequently, 3-d urinary and fecal collections were performed and analyzed for total and isotopic Zn and Cu. In the long-term study, blood, tibia and liver were also sampled for mineral status assessment. Neither short- nor long-term intake of red wine altered (67)Zn or (65)Cu absorption. In contrast, long-term (but not short-term) ethanol consumption significantly increased both (67)Zn and (65)Cu absorption compared with the control and red wine groups. The long-term consumption of ethanol or red wine did not affect blood or tissue Zn or Cu levels. In conclusion, short- or long-term consumption of red wine did not have a negative effect on intestinal absorption or tissue levels of zinc and Cu in rats.
Animals↗
Exchangeable magnesium pool masses reflect the magnesium status of rats.
A sensitive and valid marker to assess magnesium (Mg) status in humans is not available. The kinetically determined exchangeable pool masses have been used for other minerals, such as zinc and selenium, as markers of whole-body mineral status. To evaluate the validity of this relationship for Mg, we measured the exchangeable pools of Mg in rats over a range of magnesium dietary intakes. Rats weighing approximately 170 g were fed a control diet (500 mg Mg/kg), a marginally Mg-deficient diet (200 mg/kg) or a severely Mg-deficient diet (60 mg Mg/kg) for 2 wk. Subsequently, rats were administered an intravenous injection of (25)Mg, and the plasma (25)Mg disappearance curve was followed for the next 7 d. The following two methods were employed to analyze the exchangeable pools of Mg: 1) formal compartmental modeling and 2) a simplified determination of the total mass of the rapidly exchangeable Mg pool (EMgP). The mass of the three exchangeable pools (two extracellular pools and one intracellular pool) determined by compartmental analysis decreased in proportion to dietary Mg intake. EMgP, the combined pools of Mg that exchange with the plasma Mg within 48 h, decreased significantly as dietary Mg was lowered. It was positively correlated with conventional markers of Mg status (total Mg in plasma, erythrocyte and tibia Mg levels). Compartmental analysis assesses Mg exchangeable pools more accurately, but determination of EMgP is simpler and faster. Our findings demonstrate that the exchangeable pools of Mg constitute a good marker of Mg status in rats.
Animals↗
Correlation of predischarge electrocardiographic patterns with left ventricular function in patients with anterior wall myocardial infarction.
The aim of this prospective study was to assess the correlation between different predischarge electrocardiographic patterns and left ventricular function, evaluated by physical examination and echocardiography, in patients with first Q wave anterior acute myocardial infarction. A positive correlation was found between the electrocardiographic pattern and wall motion score assessed by echocardiography, reflecting a gradual worsening in left ventricular function among the different patterns. Patients with an isoelectric ST segment and negative T waves had a 73% decrease in the risk of clinical heart failure compared to those who continued to have ST elevation. Thus, a predischarge electrocardiogram can be used as a simple, noninvasive method for the risk stratification of patients with acute myocardial infarction.
Adult↗
Effects of acute and chronic coingestion of AlCl3 with citrate or polyphenolic acids on tissue retention and distribution of aluminum in rats.
Aluminum (Al) is toxic to certain biological systems and has been implicated as a neurotoxic agent in the pathogenesis of Alzheimer's disease. Intestinal absorption of Al is very low (0.1%), but many organic dietary components are potential chelators of Al and may enhance its absorption and tissue distribution. We examined the effects of acute and chronic coingestion of AlCl3 with different polyphenolic acids on Al retention and compared to citrate in rats. In experiment 1, animals fasted for 14 h were dosed orally with demineralized water, Al chloride, Al chloride plus sodium citrate, or Al chloride plus a polyphenol acid. Blood samples were taken before and 2 h after the gavage and animals were killed 6 h later. In experiment 2, the rats were adapted on a purified diet for 1 wk and received the following for 4 wk in their experimental diets: AlCl3, except group 1, plus citrate or a polyphenol acid, except groups 1 and 2. Animals were killed and blood and tissues were sampled. In experiment 1, citrate highly enhanced Al absorption and its tissue retention. Gallic and chlorogenic acids significantly increased tibia and kidney Al levels compared to the Al group. In experiment 2, Al levels in the urine were significantly increased in all the Al groups compared to the control group. Significantly higher Al levels in the tibia, kidney, and brain were observed in the citrate group and a significant increase in brain Al level was also noted in the chlorogenic acid group compared to AlCl3 group. This may suggest a possible relation structure-activity of polyphenol acids. However, further studies are necessary to better understand the influence of polyphenol acids on Al metabolism, in particular that of chlorogenic acid.
Aluminum↗
Response of diamine oxidase and other plasma copper biomarkers to various dietary copper intakes in the rat and evaluation of copper absorption with a stable isotope.
There is a lack of agreement on index of Cu status and reliable and sensitive biomarkers are still required. The purpose of this present work was to assess in rats the sensitivity of diamine oxidase (DAO) activity, a recently proposed biomarker, to modifications in dietary Cu intake in comparison with other plasma biomarkers of Cu status. We also evaluated the effect of Cu dietary level on Cu and Zn intestinal absorption. Results showed that plasma Cu and plasma caeruloplasmin were significantly decreased at day 8 compared with the control group (7.4 mg Cu/kg diet) while DAO activity was significantly decreased at day 12 of the deficient diet (0.61 mg Cu/kg diet). Cu supplementation (35 mg Cu/kg diet) had no effect on any of the studied biomarkers of Cu status. In Cu-deficient rats plasma Cu and DAO activities were normalized 4 d after return to the control diet while caeruloplasmin was normalized later, at day 11. Apparent absorption values (%) of total Cu or 65Cu isotope were significantly increased in the Cu-deficient rats compared with the other groups and similar in the control and the Cu-supplemented groups. The urinary excretion of total Cu or 65Cu isotope were increased in the Cu-supplemented group compared with the other two groups. Both apparent absorption and urinary excretion of total Zn or 67Zn isotope remained unchanged in the three experimental groups. In conclusion, DAO activity seemed to be less sensitive to Cu deficiency than plasma Cu or caeruloplasmin concentrations. The present study also showed a significant increase in Cu intestinal absorption with dietary Cu restriction but no decrease with Cu supplementation in the rat.
Absorption↗
[Implementation of a psychological support program for children with cancer in Poland. Preliminary report].
Intensive chemotherapy programme in children with cancer may result in psychological mal adjustment. Treatment facilities as well as psychological support are of great importance to minimize these side effects. In 1998 the programme of psychological support was introduced in 7 Polish paediatric haematology / oncology centres. Psychological adjustment of patients treated in each centre was examined 5 yrs after the termination of therapy. At the same time children with new diagnosis of cancer were monitored psychologically along with the psychological support programme. Psychological status of each patient was examined with the following tests: Cattell's questionnaires (CPQ, HSPQ), Manifest Anxiety Scale, Spielberger's inventories (STAI, STAIC), Wechsler Intelligence Scale. The programme of psychological support was based on guidelines of SIOP Psychosocial Committee and included such elements as informing about diagnosis and treatment, explaining any doubt, maintaining an open communication, educational care in the periods of treatment, encouraging to activity even during periods of discomfort. The analysis showed that most of the participating centres could only provide some elements of the support programme. The main problem was to convince medical staff to inform children on diagnosis and treatment plans. Preliminary results of the study indicate that full psychological support for children with cancer and their families from the beginning of therapy can result in improvement in psychological adjustment. During the ensuing period, patients and their parents appreciate the possibilities to contact a psychologist.
Adaptation, Psychological↗
Systemic administration of calmodulin antagonist W-7 or protein kinase A inhibitor H-8 prevents torsade de pointes in rabbits.
BACKGROUND: The ventricular arrhythmia torsade de pointes (TdP) occurs after QT interval prolongation and is associated with sudden cardiac death. The afterdepolarizations that initiate TdP are facilitated by protein kinase A and the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase). METHODS AND RESULTS: In this study, we evaluated the feasibility of suppression of TdP through systemic therapy with kinase inhibitory agents in an established animal model. Under control conditions, TdP was inducible in 6 of 8 rabbits. CaM kinase blockade with the calmodulin antagonist W-7 reduced TdP in a dose-dependent fashion (4 of 7 inducible at 25 micromol/kg and 1 of 7 inducible at 50 micromol/kg). Increased intracellular Ca(2+) has been implicated in the genesis of afterdepolarizations, but pretreatment with high-dose W-7 did not prevent TdP in response to the L-type Ca(2+) channel agonist BAY K 8644 (300 nmol/kg), suggesting that CaM kinase-independent activation of L-type Ca(2+) current was not affected by W-7. Compared with control animals, W-7 reduced TdP inducibility without shortening the QT interval, increasing heart rate, or reducing the blood pressure. The protein kinase A antagonist H-8 also caused a dose-dependent reduction in TdP inducibility (5 of 6 at 1 micromol/kg, 4 of 6 at 5 micromol/kg, and 0 of 6 at 10 micromol/kg), but unlike W-7, H-8 did so by shortening the QT interval. CONCLUSIONS: These findings show that the acute systemic application of W-7 and H-8 is hemodynamically tolerated and indicate that kinase inhibition may be a viable antiarrhythmic strategy.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Lipid peroxidation and antioxidant status in experimental diabetes.
Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate the oxidative stress related parameters in streptozotocin-induced diabetes in rats using different complementary approaches: susceptibility to in vitro oxidation (lipid peroxidation induction in liver homogenate, red blood cells hemolysis), blood antioxidant status (total antioxidant capacity by two approaches), and plasma isoprostane measurement, a new marker of lipid peroxidation in vivo. We have shown that induced liver thiobarbituric acid reactive substances increased after 4 weeks of diabetes, in spite of increased liver vitamin E content. Red blood cells hemolysis was significantly delayed after 4 weeks of diabetes. Plasma antioxidant capacity (AOC) tended to increase after 4 weeks of diabetes and was correlated with plasma vitamin E levels. Total antioxidant activity (TAA) significantly decreased after 1 week and a significant correlation was observed with plasma albumin levels. Plasma isoprostane (8-epiprostaglandinF2alpha) concentrations were not modified significantly 1 week or 4 weeks after the induction of diabetes. Levels of vitamin E in the diet and changes in its distribution among the body seems to play an important role in the development of oxidative stress during diabetes and its consequences.
Animals↗
Enhanced tumor necrosis factor-alpha production following endotoxin challenge in rats is an early event during magnesium deficiency.
Magnesium (Mg) plays an essential role in fundamental cellular reactions and the importance of the immuno-inflammatory processes in the pathology of Mg deficiency has been recently reconsidered. The purpose of the present study was to assess the effect of different stages of Mg deficiency on endotoxin response and tumor necrosis factor-alpha (TNF alpha) production. Weaning male Wistar rats were pair fed either a Mg-deficient or a control diet. At day 7, lipopolysaccharide (LPS) induced no lethal effects in control rats but resulted in 70% mortality in Mg-deficient rats within 3 h. The vulnerability of Mg-deficient rats to LPS was associated with higher TNF alpha plasma values. Mg-deficient animals that received magnesium supplementation before endotoxin challenge had significantly increased survival. At day 2, control and Mg-deficient rats were also subjected to endotoxin challenge with or without magnesium pre-treatment. A significant increase in TNF alpha plasma level was observed in Mg-deficient rats compared to rats fed the control diet. Mg-deficient rats that received magnesium replacement therapy before endotoxin challenge had significantly lower TNF alpha plasma values than those receiving saline before endotoxin. Thus, the results of this experiment suggest that the activated or primed state of immune cells is an early event occurring in Mg deficiency.
Animals↗
Selenium-independent epididymis-restricted glutathione peroxidase 5 protein (GPX5) can back up failing Se-dependent GPXs in mice subjected to selenium deficiency.
We have previously characterized and cloned a secreted sperm-bound selenium-independent glutathione peroxidase protein (GPX5), the expression of which was found to be restricted to the mouse caput epididymidis. Because of the lack of selenium (Se) in the active site of this enzyme, unlike the other animal GPXs characterized to date, it was suspected that GPX5 does not function in the epididymis as a true glutathione peroxidase in vivo. In the present report, following dietary selenium deprivation which is known to reduce antioxidant defenses and favor oxidative stress in relation with depressed Se-dependent GPX activities, we show that the epididymis is still efficiently protected against increasing peroxidative conditions. In this model, the caput epididymides of selenium-deficient animals showed a limited production of lipid peroxides, a total GPX activity which was not dramatically affected by the shortage in selenium availability and an increase in GPX5 mRNA and protein levels. Altogether, these data strongly suggest that the selenium-independent GPX5 could function as a back-up system for Se-dependent GPXs.
Animals↗
Relation between QT dispersion and slow intraventricular conduction in patients with acute anterior wall myocardial infarction.
BACKGROUND: QT dispersion has been proposed as a simple, noninvasive measure for identifying patients at risk of postinfarction arrhythmia. It is assumed to reflect nonuniform ventricular repolarization, which, in turn, may result from regional differences in repolarization time as well as from localized activation delay. The aim of this study was to examine the relation between QT dispersion and intraventricular conduction abnormalities in patients with acute anterior wall myocardial infarction. METHODS AND RESULTS: Standard 12-lead electrocardiographic and 12-lead signal-averaged electrocardiographic recordings were performed in 25 patients with a first Q-wave anterior wall myocardial infarction. Measures calculated by using the 6 precordial (V1 through V6) leads for QT dispersion were (1) difference between maximum and minimum QT and QTc intervals and (2) standard deviation of QT and QTc intervals. Measures calculated from the signal-averaged electrocardiogram were (1) maximum filtered QRS duration; (2) mean; and (3) standard deviation of filtered QRS duration. No relation was found between any measure of filtered QRS duration and that of QT dispersion by using linear correlation analysis. Similarly, no significant association was demonstrated between the filtered QRS duration and corresponding QT interval measurements (total 131 leads). CONCLUSIONS: The lack of correlation between signal-averaged electrocardiogram indexes of slow intraventricular conduction and electrocardiogram variables of QT dispersion suggests an independent predictive value for the 2 methods in identifying patients at risk of postinfarction arrhythmia. This suggestion is further supported by the finding that altered activation sequence is an unlikely mechanism of QT dispersion in patients with acute myocardial infarction, as indicated by the lack of association between the filtered QRS duration and corresponding QT interval measurements.
Arrhythmias, Cardiac↗
Inhibitory effect of procyanidin-rich extracts on LDL oxidation in vitro.
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Animals↗
Urine and plasma galactitol in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia.
Urinary excretion of galactitol was determined in 95 normals (N/N), 67 galactosemic (G/G), and 39 compound heterozygotes for the Duarte and galactosemia genotype (D/G). Galactitol excretion is age-dependent in both normal individuals and patients with classic galactosemia on lactose-restricted diets. In galactosemic patients who are homozygous for the Q188R mutation, urinary galactitol levels were fivefold to 10-fold higher than those of normal subjects of comparable age. All but a few patients with classic galactosemia with the Q188R mutation and another mutant G allele had urinary excretion comparable to the Q188R homozygous patients. African-American galactosemic patients with the S135L mutation of the galactose-1-phosphate uridyltransferase (GALT) gene also excreted abnormal quantities of galactitol. Most subjects with a Duarte allele and a G allele excrete normal amounts of the sugar alcohol. There is a correlation between galactitol excretion and red blood cell (RBC) galactose-1-phosphate (gal-1-P). Plasma galactitol was also elevated in galactosemic patients (3.4 to 23.2 micromol/L; undetectable in normal individuals). In contrast to the decrease in urinary galactitol with age, plasma levels remain in a narrow concentration range with no significant difference with age. Urine and plasma galactitol distinguish galactosemic patients from normals. In addition, urinary galactitol excretion may be an important parameter for the assessment of steady-state galactose metabolism in galactosemia.
Adolescent↗
Plasma levels of 8-epiPGF2alpha, an in vivo marker of oxidative stress, are not affected by aging or Alzheimer's disease.
Free radicals are likely involved in the aging process and there is a growing body of evidence that free radical damage to cellular function is associated with a number of age-related diseases such as atherosclerosis, cancer, and neurologic disorders. The present study was designed to evaluate in a healthy population the evolution with age of 8-epiPGF2alpha plasma levels, a recently proposed marker of in vivo lipid peroxidation. Moreover we investigated this marker of oxidative stress in patients with Alzheimer's disease (AD), an age-related neurodegenerative disorder in the development of which free radicals have been involved. Our results show that in the healthy population studied, despite decreased antioxidant defenses with increasing age as monitored by antioxidant capacity measurement, plasma 8-epiPGF2alpha levels were not correlated with age. Moreover, we have demonstrated that AD patients presented no modification of plasma 8-epiPGF2alpha level and no major alteration of the antioxidant status. In conclusion, the measurement of plasma 8-epiPGF2alpha did not allow us to detect alterations in oxidative stress with aging or in AD.
Adult↗
[The study of seasonal variability in the rehabilitation of bronchial asthma].
The aim of the study was to ascertain whether the seasons of the year influence the course of mild or moderate bronchial asthma, and to assess the effectiveness of respiratory kinesitherapy. In outpatients one month cycles of respiratory kinesitherapy were performed (twice a week for 45 min.) and were still repeated three times in the next seasons of the year. Spirometric and psychological examinations and also the self-evaluation of dyspnea were performed before and after each cycle. Additionally PEF was self-measured by the patients every day. It has been shown that seasons of the year influence neither the values of spirometric parameters of lung ventilation, the circadian rhythm of PEF, nor the effectiveness of respiratory kinesitherapy. However, the repeated cycles of effective breathing favourably influenced the psychic condition and reduced the subjective feeling of dyspnea, as well as improved the quality of asthmatics' life.
Adolescent↗
Accelerated thymus involution in magnesium-deficient rats is related to enhanced apoptosis and sensitivity to oxidative stress.
Experimental Mg deficiency leads to alterations in the immune response. Reduction of thymus weight and histological changes were previously observed in Mg-deficient rats after several weeks on a deficient diet, suggesting that functions of this immune organ may be affected by Mg deficiency. More recently, changes in the immune system during early Mg deficiency were shown. Thus, in the present study we examined modifications in the thymus during the early stages of Mg deficiency in weanling rats. From our results, it appears that Mg deficiency accelerates thymus involution. The assessment of apoptosis (enumeration of apoptotic cells on the basis of morphological criteria and intranucleosomal degradation of genomic DNA) showed greater values in thymuses from Mg-deficient rats as compared with controls. This was observed very early, since a significant difference was shown on the second day of deficiency, before reduced weight of thymus, which was recorded in the later period. These results indicate the relationship of accelerated thymus involution with an active process of cell death. Mg deficiency led to histological changes in the thymus. In the early stage of deficiency (second day) the presence of inflammatory cells was shown, suggesting that the inflammatory process was already occurring in the tissue studied. Later (eighth day) an increased proportion of epithelial reticular cells in the cortex was shown, indicating a remodelling process occurring in this period. Enhanced susceptibility to peroxidation also occurred very early during Mg deficiency. It may be hypothesized that disturbances in Mg status of short duration could have cellular effects with various deleterious consequences.
Animals↗