Biomedical subjects

Jürgen Vormann

Publications and source records attributed to Jürgen Vormann.

6 recordsLinked to original sources

PubMed2007

Diminished ciprofloxacin-induced chondrotoxicity by supplementation with magnesium and vitamin E in immature rats.

Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has been demonstrated previously. Identical damages can be induced in immature rats by feeding them a magnesium-deficient diet. The objective of the present study was to investigate whether, in reverse, oral supplementation with magnesium, vitamin E, or both can diminish the typical quinolone-induced arthropathy in juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats were each fed either normal feed (group A), a vitamin E-enriched diet (group B), a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats were sacrificed and cartilage samples from knee joints were examined under a light microscope for the presence of typical quinolone-induced joint cartilage lesions. In addition, magnesium, calcium, and vitamin E concentrations in cartilage and plasma were determined. In the samples from rats fed a normal diet (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups fed an enriched diet, the incidence of specific lesions (n) was significantly lower: group B, n = 10 (41% reduction compared to the incidence for group A; P < 0.05); group C, n = 6 (65% reduction; P < 0.01); and group D, n = 3 (82% reduction; P < 0.01). In comparison to the standard diet, diets with magnesium and vitamin E supplementation resulted in significantly higher magnesium and vitamin E concentrations in plasma and articular cartilage. Supplementation with magnesium and vitamin E alone or in combination may relevantly diminish joint cartilage lesions induced by quinolones in immature rats, with an additive effect of combined supplementation. The data further support the proposed pathomechanism of quinolone-induced arthropathy and the crucial role of magnesium in immature joint cartilage.

Animals↗

PubMed2006

Acid-base status affects renal magnesium losses in healthy, elderly persons.

Magnesium and calcium deficiency in humans is related to a number of pathological phenomena such as arrhythmia, osteoporosis, migraine, and fatal myocardial infarction. Clinically established metabolic acidosis induces renal losses of calcium. In normal subjects, even moderate increases in net endogenous acid production (NEAP) impair renal calcium reabsorption but no information is available whether this also influences renal magnesium handling. The aim of the study was to examine the relation between NEAP and renal magnesium excretion in healthy, free-living, elderly subjects. The subjects (age 64 +/- 4.7 y, n = 85) were randomly selected from the population register in Gothenburg (Sweden). Magnesium, calcium, and potassium were measured in 24-h urine samples and NEAP was quantified as renal net acid excretion (NAE). NAE was positively correlated with excretions of magnesium (R(2) = 0.27, P < 0.0001) and calcium (R(2) = 0.30, P < 0.0001) but not potassium. When 24-h urinary magnesium excretion was adjusted for 24-h urinary potassium excretion, a biomarker for dietary potassium intake, the association between magnesium excretion and NAE remained significant (R(2) = 0.21, P < 0.0001). The significant association between potassium-adjusted magnesiuria and NAE suggests that the acid-base status affects renal magnesium losses, irrespectively of magnesium intake. Magnesium deficiency could thus, apart from an insufficient intake, partly be caused by the acid load in the body.

Acid-Base Imbalance↗

PubMed2005

Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells.

Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects. However, the molecular mechanisms to explain pleiotrophic effects of CoQ10 are not clear yet and it is likely that CoQ10 targets the expression of multiple genes. We therefore utilized gene expression profiling based on human oligonucleotide sequences to examine the expression in the human intestinal cell line CaCo-2 in relation to CoQ10 treatment. CoQ10 caused an increased expression of 694 genes at threshold-factor of 2.0 or more. Only one gene was down-regulated 1.5-2-fold. Real-time RT-PCR confirmed the differential expression for seven selected target genes. The identified genes encode proteins involved in cell signalling (n = 79), intermediary metabolism (n = 58), transport (n = 47), transcription control (n = 32), disease mutation (n = 24), phosphorylation (n = 19), embryonal development (n = 13) and binding (n = 9). In conclusion, these findings indicate a prominent role of CoQ10 as a potent gene regulator. The presently identified comprehensive list of genes regulated by CoQ10 may be used for further studies to identify the molecular mechanism of CoQ10 on gene expression.

Antioxidants↗

PubMed2002

Synergistic effect of ofloxacin and magnesium deficiency on joint cartilage in immature rats.

Single high oral doses of fluoroquinolones (e.g., 1,200 mg of ofloxacin/kg of body weight) are chondrotoxic in juvenile rats. Characteristic cartilage lesions are detectable as early as 12 h after treatment. Since this dosing regimen does not reflect the therapeutic situation, we studied the effects of a 5- or 7-day treatment with ofloxacin at lower oral doses (10, 30, and 100 mg/kg twice a day [b.i.d.]) on joint cartilage in 4-week-old rats. We additionally investigated whether the effects of ofloxacin under these conditions are enhanced in animals kept on a magnesium-deficient diet during treatment. Knee joints were examined histologically. The concentrations of ofloxacin and magnesium were determined in plasma and cartilage. The lowest ofloxacin dose at which cartilage lesions occurred in animals on a standard diet was 100 mg/kg b.i.d. for 5 days. Peak plasma ofloxacin levels were approximately 10 mg/liter in these rats and thus were in the same range as the levels in the plasma of humans during therapy with high doses of ofloxacin. Treatment with 30 mg of ofloxacin/kg b.i.d. for 7 days caused no cartilage lesions in rats on a standard diet, but lesions did occur in 10 of 12 rats that were simultaneously fed a magnesium-deficient diet. Magnesium concentrations in bone, plasma, and cartilage from animals on an Mg(2+)-deficient diet were significantly lower than those in the controls. The concentration in plasma from animals on an Mg(2+)-deficient diet was 0.27 +/- 0.03 mmol/liter, whereas it was 0.88 +/- 0.08 mmol/liter in plasma from rats on a standard diet (means +/- standard deviations). Ofloxacin treatment did not change the total magnesium concentrations in tissues, as determined with ashed samples. The incidence of ofloxacin-induced lesions was higher in the magnesium-deficient animals, suggesting a synergistic effect. These results must be taken into account for a benefit-risk evaluation if ofloxacin is considered for use in the pediatric population.

Animals↗

PubMedDate not supplied

Magnesium: nutrition and metabolism.

Magnesium is an essential mineral that is needed for a broad variety of physiological functions. The usual daily magnesium uptake with a western diet is sufficient to avoid deficiency but seems not to be high enough to establish high normal serum magnesium concentrations that are protective against various diseases. Changes in magnesium homeostasis mainly concern the extracellular space, as the intracellular magnesium concentration is well regulated and conserved. The extracellular magnesium concentration is primarily regulated by the kidney, the mechanisms of this regulation have been elucidated recently. Due to the growing knowledge about the regulation of extra- and intracellular magnesium concentrations and the effects of changed extracellular magnesium levels the use of magnesium in therapy gains more widespread attention.

Animals↗

PubMedDate not supplied

Magnesium and hearing.

The last several decades have revealed clinical and experimental data regarding the importance of magnesium (Mg) in hearing. Increased susceptibility to noise damage, ototoxicity, and auditory hyperexcitability are linked to states of Mg deficiency. Evidence for these processes has come slowly and direct effects have remained elusive because plasma Mg levels do not always correlate with its deficiency. Despite the major progress in the understanding of cochlear mechanical and auditory nerve function, the neurochemical and pharmacologic role of Mg is not clear. The putative mechanism suggests that Mg deficiency may contribute to a metabolic cellular cascade of events. Mg deficiency leads to an increased permeability of the calcium channel in the hair cells with a consequent over influx of calcium, an increased release of glutamate via exocytosis, and over stimulation of NMDA receptors on the auditory nerve. This paper provides a current overview of relevant Mg metabolism and deficiency and its influence on hearing.

Calcium Channels, L-Type↗