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Biomedical subjects

A Mazur

Publications and source records attributed to A Mazur.

At least 37 records · Page 2Linked to original sources
PubMed2002

Morphological and immune response alterations in the intestinal mucosa of the mouse after short periods on a low-magnesium diet.

The importance of Mg for the immune function is well recognized; however, there is no information available about the effect of Mg intake on the modulation of local immune response in the intestine. Thus, in the present study the hypothesis that short periods of Mg deprivation can affect intestinal mucosa and local immune response was tested. For this purpose, OF1 female mice were fed a semipurified diet (1000 mg Mg/kg diet). For 3 d before immunization and 1 d after, half of the animals were fed a Mg-deficient diet (30 mg Mg/kg diet), three immunizations per os were performed every 3 weeks with Escherichia coli producing the CS31A capsule-like protein (1010 or bacteria per animal). Mice were killed 10 d after the last immunization. The level of specific anti CS31A immunoglobulin (Ig) G and IgA in the serum and secretory IgA in the intestinal secretions and faeces were measured by ELISA. The results indicated that administration of a high dose of immunogen with a low-Mg diet led to lower specific IgA levels in the intestinal mucus and serum. Administration of a low dose of immunogen with a low-Mg diet led to lower IgA and IgG levels in the serum and secretory IgA coproantibodies. To assess alterations of intestinal mucosa caused by a low-Mg diet for a short period, histological and scanning electron microscopy analyses were performed on samples from mice (not submitted to the vaccination protocol) after 3 d on the Mg-deficient diet. These analyses showed several alterations, suggesting perturbations in the growth of the intestinal mucosa. These changes were accompanied by modifications in the expression of several genes involved in cell growth and stress response. From this present work, it may be concluded that short periods of Mg deprivation can affect the intestinal mucosa and local immune response of the intestine.

Animals↗
PubMed2002

Stress protein expression cDNA array study supports activation of neutrophils during acute magnesium deficiency in rats.

Recent studies underline the importance of the immunoinflammatory processes in the pathology of acute magnesium (Mg)-deficiency. The aim of this study was to assess the effect of acute experimental Mg-deficiency in the rat on neutrophil activity. Weaning male Wistar rats were fed either a Mg-deficient or a control diet for 8 days. In this experiment, we measured neutrophil respiratory burst by chemiluminescence; then, to examine the molecular events associated with acute Mg-deficiency, we applied cDNA array technology to define the transcription response in neutrophils of Mg-deficient rats in comparison with controls. In Mg-deficient rats, the characteristic inflammatory response was accompanied by a marked increase in the number of neutrophils. Moreover, as shown by chemiluminescence studies, basal neutrophil activity from Mg-deficient rats was significantly elevated when compared to neutrophils from control rats. Moreover, the chemiluminescence of neutrophils from Mg-deficient rats was significantly higher than that of control rats following phorbol myristate acetate or opsonized zymosan activation. Using cDNA array which includes 207 known rat genes of stress proteins, 102 genes were found to be expressed in neutrophils. Among expressed genes, 78 per cent of genes were found to be expressed more than twofold in neutrophils from Mg-deficient rats compared to control rats. Acute Mg-deficiency was characterized by an induction of genes encoding for proteins involved in apoptosis, heat shock proteins, protein belonging to the cytoskeleton, proteins implicated as stress response regulators and effectors and enzyme implicated in thromboxane synthesis. Then, this experimental strategy allowed to identify a series of genes implicated in the immunoinflammatory process of Mg-deficiency.

Animals↗
PubMed2002

High magnesium concentration in vitro decreases human leukocyte activation.

In view of experimental data suggesting that pharmacological magnesium (Mg) therapy could be expected to temper hypersensitivity, the aim of the present study was to assess the effect of in vitro high Mg concentration (8 mmol/l vs. 0.8 mmol/l) on human leukocyte activation. The first experiment in nine healthy volunteers was performed on total leukocyte suspension containing 82 +/- 4 per cent of neutrophils. The results demonstrate the inhibitory effect of high Mg concentration as shown by the significant reduction of superoxide anion production following phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP) activation. Moreover, neutrophils activated with fMLP showed an increased respiratory burst when incubated in low Mg concentration (0.2 mmol/l) as compared to normal Mg concentration (0.8 mmol/l). Similarly, high concentration of Mg resulted in a significant reduction in superoxide anion production by eosinophils in response to PMA in five eosinophilic patients. In patients showing Hymenoptera venom hypersensitivity, high Mg concentration resulted in a significant reduction of sulphidoleukotrienes production by leukocytes in response to venom allergen (six patients) or in response to zymosan activated particules (fourteen patients). Taken together, the results suggests that Mg acts via a non specific mechanism and appears to be non specific to a particular cell type. As Mg counteracts calcium in many physiological and pathological processes, it is reasonable to hypothesise that extracellular Mg can diminish leukocyte activation by its calcium antagonism.

Anions↗
PubMed2002

Measurement of steroid levels in saliva in a population-based survey of lifestyle, medical conditions, marriage, sex life and hormone status in aging men: a feasibility study.

Some population-based studies on male aging measure testosterone and cortisol in saliva instead of serum, but very few measure estradiol and dehydroepiandrosterone sulfate (DHEA-S), suggesting further testing is needed for reliability and comparative validity. In addition, the effects of interview stress and circadian hormone secretion need to be checked. In a pilot study on the overall sexual capacity of aging men, 48 randomly selected, healthy, heterosexual, cohabiting men aged 50-80 years, from Mannheim, Germany, and 50 from the State College, Pennsylvania, USA, were administered a standardized interview covering medical biography, present and previous life and work, marriage and emotional status. Two saliva samples were collected from each subject for measurement of testosterone, cortisol, estradiol and DHEA-S levels before and after the interview, and each subject completed a confidential self-administered questionnaire on intercourse, masturbation, orgasm, fantasies, libido and arousal. Questionnaires, hormone measurement techniques and the survey protocol had been extensively pretested. Prior to the pilot study, the kits for measuring testosterone and DHEA-S in saliva were checked for comparative validity against established measuring techniques in serum in 31 cases for testosterone and in 24 different cases for DHEA-S. These 55 cases underwent clinical diagnosis and were not otherwise involved in this study. The cases had been referred to the Andrology Unit of the University Hospital, Marburg, for reasons unrelated to this study. Given the biological differences for both steroids between their presence in blood and in saliva, a perfect correspondence between the two values was not expected and was not observed. The correlations obtained, however, support the assumption that all statistical relationships between testosterone and DHEA-S values in serum and clinical, as well as behavioral, variables reported to date may be replicated for testosterone and DHEA-S values in saliva.

Aged↗
PubMed2001

Pause-dependent polymorphic ventricular tachycardia during long-term treatment with dofetilide: a placebo-controlled, implantable cardioverter-defibrillator-based evaluation.

OBJECTIVES: To compare the incidence of pause-dependent polymorphic ventricular tachycardia (PVT) in patients with implantable cardioverter-defibrillators (ICDs) randomly assigned to the QT-prolonging antiarrhythmic dofetilide or placebo. BACKGROUND: Drug-related torsade de pointes (TdP) is usually recognized within days of initiating therapy, but its incidence during long-term therapy is unknown. METHODS: We assessed the frequency of TdP and ICD electrograms compatible with TdP in a multicenter study that randomized ICD patients to placebo (n = 87) or dofetilide (n = 87). As reported elsewhere, the number of patients with a primary trial end point (ICD intervention for VT or ventricular fibrillation) was similar in the two groups. For this analysis, a qualifying event was TdP (on electrocardiogram) or an intracardiac electrogram showing pause-dependent PVT. RESULTS: A total of 620 electrograms obtained in 131 patients were analyzed blindly by prospectively defined criteria for episodes of pause-dependent polymorphic VT. These were identified in 15/87 (17%) patients receiving dofetilide and 5/87 (6%) patients on placebo (p < 0.05). Five of these episodes were early (<3 days), all of which were TdP on dofetilide. There were 15 late events, 10 on dofetilide and five on placebo (p = 0.29). The median time to a late event was 22 days (range 6 to 107 days) for dofetilide and 99 days (range 34 to 207 days) for placebo. CONCLUSIONS: Pause-dependent PVT was more common among patients receiving dofetilide, although total VT incidence was similar in the two groups. These data suggest that in ICD patients either long-term dofetilide therapy is associated with an increased risk of TdP or the drug alters VT morphology.

Anti-Arrhythmia Agents↗
PubMed2001

Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency.

Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats.

1. Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. 2. Hyperalgesic Mg-deficient rats were administered intrathecally (10 microl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. 3. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 micromol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 micromol x kg(-1), i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. 4. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.

2-Amino-5-phosphonovalerate↗
PubMed2001

Functional similarity between electrograms recorded from an implantable cardioverter defibrillator emulator and the surface electrocardiogram.

Clinical use of stored electrogram (EGM) configurations currently used in ICDs is limited. The hypothesis that EGMs recorded from electrodes on the ICD surface may improve diagnostic capabilities of the device was tested in the present study. The Buttons on Active Can Emulator (BACE), an ICD-sized device containing four button electrodes, was temporarily placed into a subcutaneous or submuscular left pectoral pocket in 16 patients during ICD implantation. Simultaneous recordings were obtained from the ECG lead II, bipolar EGMs using BACE electrodes, and a bipolar atrial EGM during sinus rhythm (SR), ventricular pacing (VP) at cycle lengths of 500 and 400 ms, and VT. Visible P waves were present in all patients during SR (n = 15), in 5 (33%) of 15 patients during VP, and none of the patients during VT (n = 4) using BACE EGMs and lead II. P and QRS amplitudes and the P:QRS ratio during SR in BACE EGMs were significantly lower than those in lead II. BACE EGMs showed prominent changes in QRS morphology and duration during VP and VT compared to SR, and the magnitude of QRS prolongation during VP was similar to that in lead II. Measurements of PR, QRS, and QT duration during SR showed good agreement between BACE EGMs and lead II. In conclusion, EGMs recorded from electrodes embedded on the ICD housing may potentially improve visual discrimination between supraventricular and ventricular arrhythmias. They also may be useful as a surrogate of the ECG for analysis and monitoring of different components of P-QRS-T complex.

Defibrillators, Implantable↗
PubMed2001

Biases about man-made cancer among researchers.

Can sociological variables significantly predict researchers' positions on a scientific issue? Carcinogenesis offers a good test case because it is not definitively established how important man-made substances are as contributors to human cancer. American cancer researchers divide on this issue, some broadly emphasizing the importance of man-made carcinogens, others consistently minimizing their importance relative to natural carcinogens. We find that cancer researchers who are male, are affiliated with a medical school, and have more publications, are more likely than their colleagues to minimize the importance of man-made carcinogens.

Disease↗
PubMed2001

Isolation and sequencing of Rhizobium leguminosarum Bv. Trifolii PssN, PssO and PssP genes encoding the proteins involved in polymerization and translocation of exopolysaccharide.

Rhizobium leguminosarum bv. trifolii produces an acidic exopolysaccharide (EPS) that plays an important role in symbiotic interaction with clover plants. The sequence of 6.0-kb DNA fragment located upstream of the previously described prsDEorf3 and pssCDE genes involved in exopolysaccharide biosynthesis revealed three new genes designated pssN, pssO and pssP. The predicted protein product of pssP gene shares a significant homology to members of the membrane-periplasmic auxiliary (MPA1) family, that are involved in polymerization of the repeating subunits of EPS. The putative pssN protein product is highly homologous to the family of the outer membrane auxiliary (OMA) proteins engaged in translocation of polysaccharides in bacteria. The PssO did not reveal homology to the known bacterial proteins, but showed characteristic features of outer membrane proteins, and with PssN and PssP, it might be a part of the system involved in polymerization and translocation of EPS across the bacterial membranes.

Amino Acid Sequence↗
PubMed2001

Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.

Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.

4-Quinolones↗
PubMed2000

Inflammatory response following acute magnesium deficiency in the rat.

The importance of inflammatory processes in the pathology of Mg deficiency has been recently reconsidered but the sequence of events leading to the inflammatory response remains unclear. Thus, the purpose of the present study was to characterize more precisely the acute phase response following Mg deficiency in the rat. Weaning male Wistar rats were pair-fed either a Mg-deficient or a control diet for either 4 or 8 days. The characteristic allergy-like crisis of Mg-deficient rats was accompanied by a blood leukocyte response and changes in leukocytes subpopulations. A significant increase in interleukin-6 (IL-6) plasma level was observed in Mg-deficient rats compared to rats fed a control diet. The inflammatory process was accompanied by an increase in plasma levels of acute phase proteins. The concentrations of alpha2-macroglobulin and alpha1-acid glycoprotein in the plasma of Mg-deficient rats were higher than in control rats. This was accompanied in the liver by an increase in the level of mRNA coding for these proteins. Moreover, Mg-deficient rats showed a significant increase in plasma fibrinogen and a significant decrease in albumin concentrations. Macrophages found in greater number in the peritoneal cavity of Mg-deficient rats were activated endogenously and appeared to be primed for superoxide production following phorbol myristate acetate stimulation. A high plasma level of IL-6 could be detected as early as day 4 for the Mg-deficient diet. Substance P does not appear to be the initiator of inflammation since IL-6 increase was observed without plasma elevation of this neuropeptide. The fact that the inflammatory response was an early consequence of Mg deficiency suggests that reduced extracellular Mg might be responsible for the activated state of immune cells.

Acute-Phase Proteins↗
PubMed2000

The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers.

A multicenter European study (FoodCue) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo. The present work describes the effect of Cu supplementation on (2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people. Double-blinded copper supplementation was achieved in 26 healthy volunteers (50-70 years) with pills containing 3 mg CuSO(4), 3 mg Cu glycine chelate (CuG) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout (WO) on placebo. The results show significant increases in time necessary to achieve 50% hemolysis (LT(50)) after 3CuSO(4) and 6CuG compared with values after WO periods. Cu supplementation did not increase the levels of (Cu,Zn)SOD activity in red blood cells. Resistance to hemolysis was significantly and positively correlated (r =.30, p <.01) with alpha- and beta-carotene content in the plasma. Together, these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation. The decreased oxidizability of red blood cells did not result from increased (Cu,Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content.

Aged↗
PubMed2000

Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members.

Extracellular lipolytic activity enabled the human pathogen Candida albicans to grow on lipids as the sole source of carbon. Nine new members of a lipase gene family (LIP2-LIP10) with high similarities to the recently cloned lipase gene LIP1 were cloned and characterised. The ORFs of all ten lipase genes are between 1281 and 1416 bp long and encode highly similar proteins with up to 80% identical amino acid sequences. Each deduced lipase sequence has conserved lipase motifs, four conserved cysteine residues, conserved putative N-glycosylation sites and similar hydrophobicity profiles. All LIP genes, except LIP7, also encode an N-terminal signal sequence. LIP3-LIP6 were expressed in all media and at all time points of growth tested as shown by Northern blot and RT-PCR analyses. LIP1, LIP3, LIP4, LIP5, LIP6 and LIP8 were expressed in medium with Tween 40 as a sole source of carbon. However, the same genes were also expressed in media without lipids. Two other genes, LIP2 and LIP9, were only expressed in media lacking lipids. Transcripts of most lipase genes were detected during the yeast-to-hyphal transition. Furthermore, LIP5, LIP6, LIP8 and LIP9 were found to be expressed during experimental infection of mice. These data indicate lipid-independent, highly flexible in vitro and in vivo expression of a large number of LIP genes, possibly reflecting broad lipolytic activity, which may contribute to the persistence and virulence of C. albicans in human tissue.

Amino Acid Sequence↗
PubMed2000

Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation.

Adult↗