Biomedical subjects
H Pagel
Publications and source records attributed to H Pagel.
O2-supply to the kidneys and the production of erythropoietin.
The concentration of erythropoietin (Ep) in blood increases little following a reduction of the renal blood flow (rbf). In the present study we examined whether a reduction of rbf in rats induces a lowering of the renal venous PO2. In addition, the combined effects of reduced rbf and hypobaric hypoxia on the production of Ep were studied. To lower rbf, silver clips with stepwisely reduced inner diameters were applied on both renal arteries. The PO2 of renal venous blood decreased gradually to values below 10 mm Hg, when rbf was reduced from 80 to 10% of normal. Under these conditions plasma Ep increased only moderately from 20 +/- 6 to 69 +/- 24 mU/ml within 18-20 h. However, plasma Ep of rats exposed to hypobaric hypoxia (stimulated altitude of 6000 m for 18-20 h) was 431 +/- 68 mU/ml, when rbf was 100-80% of normal, compared to 931 +/- 91 mU/ml, when rbf was reduced to 40-10%. Thus, a reduction of the blood flow to the kidney appears to be no major stimulus for the production of Ep, even when the PO2 in the kidney becomes very low. However, plasma levels of Ep increase markedly, when the whole body O2 offer is lowered. These results support the view that Ep production is not only dependent on the PO2 in the kidney but also under the control of extrarenal O2 sensitive mechanisms. For example, the hypothalamic-hypophyseal system is thought to influence the production of Ep.
Erythropoietin and blood pressure.
Explore the source record for details and available documents.
A comparison of the effects of renal artery constriction and anemia on the production of erythropoietin.
It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoietin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.
Pharmacokinetics of aldosterone in patients with Addison's disease: effect of rifampicin treatment on glucocorticoid and mineralocorticoid metabolism.
Treatment of tuberculosis with rifampicin in patients with pre-existing adrenal failure has been reported to induce adrenal crisis due to alteration of cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half-life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6-beta-hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P450 dependent enzymes. Infusion of aldosterone at a constant rate of 0.17 mg/h over 4.5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean +/- SD, 1649 +/- 144 vs 1586 +/- 80 pg/ml, respectively). The disappearance curve of IR-aldosterone from plasma was biexponential. No change could be observed in the plasma half-lives (alpha-phase 29 +/- 1.9 min vs 30 +/- 1.5 min, beta-phase 129 +/- 3.2 min vs 126 +/- 4.3 min), the MCR (1.47 +/- 0.1 l/h/kg vs 1.46 +/- 0.1 l/h/kg), and the volume of distribution (9.9 +/- 1.9 vs 10.2 +/- 0.3 l). The antipyrine half-life decreased significantly from 12.2 +/- 2.6 h to 7.6 +/- 0.9 h (P less than 0.05) with a rise in antipyrine clearance from 0.38 +/- 0.07 to 0.80 +/- 0.23 ml/min/kg (P less than 0.05) and no change in the volume of distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
[Studies on the effects of atrazine and simazine on the N-binding bacteria Azotobacter and Beijerinckia in the ferralitic soils of Cuba].
In two Cuban locations (Santiago de las Vegas and Jovellanos) the effect was investigated of increasing atrazin and simazin applications (0, 4, 8, 16 kg/ha) to the number of Azotobacter and Beijerinckia colonies in weakly ferrallitic soils 7 and 15 days after their application during the rainy and dry seasons. The results were as follows: 1. The number of the Beijerinckia colonies is higher in all variants than that of Azotobacter. 2. Beijerinckia and Azotobacter are stimulated up to 7 days, partly also up to 15 days, after application of the triazins. Atrazin exhibits a stronger and more lasting effect than simazin, and Azotobacter are influenced more strongly than Beijerinckia. 3. This stimulation can be adduced with a high degree of probability to the inhibition of organisms which have an antagonistic effect on N-binding bacteria.
Comparative investigations into the content of available molybdenum in important soils of the arid and humid tropics.
The determination of the content of available molybdenum in 196 soil samples from different geographical (Yemen, Sudan, Tanzania, Ghana, Cuba, and Sri Lanka) and climatic (annual precipitation 30-3000 mm) regions gave these results: 1. Arid and subarid soils of dry regions as well as rendzina-type soils contained the highest amount of available molybdenum (0.216 ppm respectively). The lowest content was determined in the ferrallitic soils of the humid tropics (0.045 ppm). These differences are mainly attributed to high pH values and CaCO3 content in aridisols and rendzina-type soils and to a strongly acid soil reaction in ferrallitic soils. 2. The content of available molybdenum was significantly positively correlated with the pH, percentage base saturation, CEC and exchangeable Ca; it was negatively correlated with the clay content. 3. Deficiency of molybdenum is hardly to be expected in arid and subarid soils (24 per cent of all samples deficient). The proportion of samples with a low Mo content and the probability of Mo deficiency increases in this order: vertisols (40%) leads to fersiallitic soils (64%) leads to ferallitic soils (89%).
Virulence factors of Escherichia coli contribute to acute renal failure.
BACKGROUND: The development of acute renal failure (ARF) significantly enhances the mortality of patients with Gram-negative septic shock. The role of specific bacterial virulence factors different from lipopolysaccharides (LPS) in the deterioration of renal function in septic shock remains to be determined. METHODS: An Escherichia coli wild-type strain (536/21 WT, O6:K15:H31) was isolated from a patient suffering from a urinary tract infection. The strain expresses various virulence factors (e.g. hemolysin, fimbriae) genetically encoded by pathogenicity islands. The spontaneous deletion mutant 536/21 Del lacks the expression of these virulence factors. Isolated rat kidneys were perfused with a suspension (5 x 10(4)/ml) of the respective strain or control perfusion medium and the renal functional parameters were analyzed. Intrarenal deposition of E. coli was detected by immunohistology and Gram staining. RESULTS: The perfusion of the isolated perfused rat kidney with a uropathogenic E. coli wild-type strain (536/21 WT) caused an acute deterioration of renal function which was not observed in kidneys exposed to a deletion mutant of E. coli 536/21 lacking the expression of virulence factors. The glomerular filtration rate and the urine flow rate significantly decreased only in kidneys perfused with the E. coli wild-type strain, while there was no change versus controls in kidneys perfused with the deletion mutant. CONCLUSIONS: Distinctive bacterial virulence factors different from LPS such as hemolysin and the presence of different fimbriae may contribute to the development of ARF in sepsis induced by E. coli. Anti-LPS strategies may not be sufficient to reduce the risk of ARF in Gram-negative septic shock.
On the glomerular mechanism of the renal protein excretion. Studies in the isolated perfused rat kidney.
The glomerular permeability of the isolated perfused kidney is manifold higher than in vivo, although structural changes at the glomerular filtration barrier are not described. It has been proposed that in vivo high molecular weight plasma proteins are concentrated at the glomerular endothelium forming an additional filtration barrier ('concentration polarization'). To test this hypothesis, isolated rat kidneys were perfused with substrate-enriched Krebs-Henseleit solutions containing albumin (50 g/l) or albumin/globulin (40/10 g/l), or with plasma. The pO2 was 675 mm Hg. Furthermore, experiments were carried out with the addition of erythrocytes with and without a reduced O2 supply (pO2 35 mm Hg). Independent of the composition of the perfusate a continuously increasing glomerular permeability was observed immediately after perfusion was started. After about 10 min, a steady state value for the glomerular permeability was reached. The addition of globulin to the perfusate or perfusion with plasma did not prevent the initial increase of the permeability. However, after addition of 5% erythrocytes to the perfusate the increase of permeability was much less pronounced. Neither the reduction of the O2 supply nor the addition of erythrocytes to a higher concentration than 5% had any further effect on the glomerular permeability. These data show that concentration polarization of high molecular weight proteins does not take place at the endothelium of the glomerulus. Independent of their ability to carry O2 erythrocytes play an important role in the glomerular filtration process.