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M Wolgast

Publications and source records attributed to M Wolgast.

At least 19 recordsLinked to original sources
PubMed2004

N-acetylaspartate levels of left frontal cortex are associated with verbal intelligence in women but not in men: a proton magnetic resonance spectroscopy study.

The left frontal cortex plays an important role in executive function and complex language processing inclusive of spoken language. The purpose of this work was to assess metabolite levels in the left and right prefrontal cortex and left anterior cingulum by proton magnetic resonance spectroscopy and relate results to verbal intelligence (Wechsler Adult Intelligence Scale revised) in a sample of college-educated healthy volunteers (dorsolateral prefrontal cortex [DLPFC]: n=52, 23 females, and left anterior cingulum: n=62, 22 females; age range: 20-75 years). In women only, N-acetylaspartate in the DLPFC and in the left anterior cingulate cortex was positively correlated with vocabulary scores. Our data support the hypothesis of existing gender differences regarding the involvement of the left frontal cortex in verbal processing as reflected in different correlations of specific metabolites with verbal scores.

Adult↗
PubMed2003

Perfusate composition influences nitric oxide homeostasis in rat juxtamedullary afferent arterioles.

AIM: Vascular diameters in isolated juxtamedullary nephron preparations perfused with cell-free solutions differ from those perfused with blood. In the present study, the effects of the albumin content of the perfusate on the afferent arteriolar diameter and endothelial nitric oxide were investigated in the isolated juxtamedullary nephron preparation perfused with Krebs-Ringer-bicarbonate buffer containing albumin in different concentrations. METHODS: The endothelium was loaded with DAF-FM DA, a nitric oxide-sensitive fluoroprobe. Perfusion was maintained either with 4% (control group), 10 or 20% albumin in the perfusate or with L-NAME (10-4 m) added to the perfusate. Fluorescent images were obtained and stored for evaluation of DAF-FM fluorescence and vascular diameters (in mid-afferent arterioles) immediately before perfusate change and every 15 min thereafter, for a 2-h period. RESULTS: Increasing the albumin concentration resulted in a decrease in fluorescence. The most rapid decline of fluorescence was obtained following L-NAME administration (relative fluorescence after 2 h: 4% albumin 92.4 +/- 5.3%; 10% albumin 79.5 +/- 4.2%; 20% albumin 66.2 +/- 2.6%; L-NAME 55.4 +/- 3.0%; mean +/- SD, n = 5). A dose-dependent constriction of the afferent arterioles was observed (normalized diameter: 4% albumin 99.8 +/- 3.0%; 10% albumin 80.3 +/- 3.3%; 20% albumin 74.3 +/- 3.2%; L-NAME 70.6 +/- 3.5%). CONCLUSION: We propose that albumin interferes with arteriolar nitric oxide homeostasis, probably by scavenging nitric oxide intra-luminally. In this respect, albumin acts similarly to red blood cells in the circulation. The magnitude of the scavenging determines the effectiveness of autoregulation in the perfused preglomerular vessels. The scavenging properties of the perfusing fluid are important in setting operating levels of endothelial nitric oxide.

Albumins↗
PubMed2003

Visualization of nitric oxide production and intracellular calcium in juxtamedullary afferent arteriolar endothelial cells.

AIM: Nitric oxide (NO) is an important signal transmitter with multiple haemodynamic functions in the kidney. Study of these is complicated by the difficulty in measuring NO directly or visualizing its production. Recently the synthesis of a group of new NO-sensitive fluorescent dyes, diaminofluoresceins (DAF), suitable for imaging applications has been reported. We attempted to use one DAF (DAF-2 DA) to investigate the relationship between endothelial calcium, NO production and afferent arteriolar reactivity. METHODS: We used the isolated, perfused juxtamedullary nephron preparation (JMN) and loaded the afferent arteriolar endothelium with Fura-2 AM and DAF-2 DA (4,5-diaminofluorescein-2-diacetyl). After in vitro calibration of the imaging system, we measured Fura-2 and DAF-2 fluorescence in single endothelial cells of afferent arterioles (AA) perfused at a pressure of 100 mmHg. RESULTS: Carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO) (10-3 m), a specific NO scavenger, decreased DAF-2 fluorescence in the endothelium by 16.1% and the mid-afferent arteriolar diameter by 10.2%, and increased endothelial calcium by 17.8%. Nomega-nitro-l-arginine methyl ester (l-NAME) (10-4 m) decreased fluorescence intensity of DAF-2 by 18.6%, increased cellular calcium level by 19.7% and constricted the vessels by 11.6%. Addition of carbachol (10-4 m) increased average DAF-2 fluorescence by 22.8% and endothelial calcium concentration by 28.9%, whereas the arteriolar diameter remained essentially unchanged. Carbachol failed to increase DAF-2 fluorescence when administered after l-NAME pre-treatment. CONCLUSION: We conclude that endothelial NO homeostasis is an important determinant of AA reactivity and suggest that DAF are suitable for real-time imaging of afferent arteriolar NO production in the isolated, perfused JMN and may be used in combination with calcium-sensitive fluorophores. We have found that NO reduction by carboxy-PTIO or l-NAME increases endothelial calcium, suggesting involvement of calcium signalling in an autocrine NO production feedback in the endothelium. This method should help to further clarify the role of endothelial NO in renal haemodynamics.

Animals↗
PubMed2001

Failure of loop diuretics to improve the long term outcome of ischaemic damage in rat kidneys.

The effects of furosemide administered at the onset of postischaemic renal failure were investigated in Sprague-Dawley rats one month after exposing the left kidney to 45 min of renal ischemia. In the experimental group, 13 mg furosemide was given intravenously both before and a few minutes after induction of the ischaemia and then, by an osmotic pump, in a daily dose of 2-3 mg for the following 7 days. The animals of the control group were treated similarly but with saline alone. After one month, the glomerular filtration rate (GFR) in the damaged left kidneys of the furosemide-treated rats was 0.5+/-0.08 ml/min, which was not significantly different from that in the untreated control rats, of 0.8+/-0.14 ml/min. As expected, the right intact kidneys responded with an increase in GFR to about 2 ml/min. Further effects that were similar in the damaged kidneys of the furosemide-treated and untreated animals were a decrease in potassium secretion and in the urine concentration ability; the urine osmolality in the diseased left kidneys was thus 1000-1500 mOsm/kg, as against over 2000 mOsm/kg in the right, intact kidneys. The function of the individual nephrons in terms of such variables as single nephron filtration rate, fractional fluid reabsorption and tubular and vascular hydrostatic pressures remained unaltered, however. Hence, the severe reduction in whole kidney GFR appeared to be due to a loss of nephrons rather than to an equal decrease in each individual nephron. It is also clear that furosemide did not improve the long-term outcome of acute postischaemic renal failure.

Acute Kidney Injury↗
PubMed1998

Influence of the sympathetic nervous system on renal function during hypothermia.

Hypothermia increases preglomerular vasoconstriction leading to decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Since plasma catecholamine concentrations are increased during hypothermia, the present study was performed to determine the role of the renal sympathetic nervous system in the cold-induced renal vasoconstriction. In Inactin anaesthetized rats, hypothermia at 28 degrees C decreased GFR by 50% but failed to alter efferent renal sympathetic nerve activity (ERSNA). Since hypothermia causes shivering which could have influenced the ERSNA recording, Inactin anaesthetized rats were treated with pethidine or rats were anaesthetized with pentobarbital sodium or Saffan to eliminate cold-induced shivering. In these non-shivering rats, hypothermia produced a reversible decrease in ERSNA in association with a fall in GFR that was of a similar magnitude as in shivering rats. Further studies in Inactin anaesthetized rats showed that the fall in GFR was unaltered by renal denervation, bilateral adrenalectomy or intrarenal administration of the alpha 1-adrenoceptor antagonist prazosin. We conclude that cold-induced renal vasoconstriction is not due to an increase in ERSNA or adrenaline/noradrenaline-mediated activation of renal alpha 1-adrenoceptors.

Adrenalectomy↗
PubMed1998

The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat.

The aim of this study was to investigate whether the increased diuresis in consequence of hypothermia is due to a depression of the hypothalamic release of antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and the effect of intravenous (i.v.) administration of 65 ng kg-1 desmopressin (selective V2-receptor agonist) were determined in the anaesthetized rat. In spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P < 0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma antidiuretic hormone decreased from 7.5 +/- 1.1 to 3.8 +/- 0.4 pg mL-1 (P = 0.01). After injection of desmopressin urine flow was completely restored, whereas urine osmolality and sodium excretion were only partially normalized. Since tubular conservation of water and fractional water reabsorption decreased during hypothermia, the diuresis must have resulted from an augmented loss of water. This is further supported by the fact that osmolal excretion was not influenced either by hypothermia or by desmopressin. It is concluded that the diuresis in consequence to hypothermia is due both to a decrease in the release of ADH and to a reduction of renal medullary hypertonicity.

Anesthesia↗
PubMed1996

Characteristics of the glomerular capillary membrane of the rat kidney as a hydrated gel. I. Hypothetical structure.

It is suggested that the glomerular capillary membrane constitutes a flexible gel, where negative charges fixed to the matrix of the membrane account for the maintenance of its integrity. In this model, the hydrostatic pressure throughout the membrane is assumed to equal the glomerular capillary pressure. Pglom. of 56.7 mmHg. On the plasma side of the membrane, the charge-induced electro-osmotic pressure therefore has to balance the colloid osmotic pressure of glomerular plasma, and on its Bowman's space side, it has to balance the pressure drop. Pglom-PBow, across this interphase. Using micropuncture technique, the glomerular plasma colloid osmotic pressure of 20.6 mmHg was found to require a charge density of 24.8 mEq L-1 and the pressure drop at the Bowman's space side of 56.7-12.2 = 44.5 mmHg a density of 36.6 mEq L-1. The transmembranous electric potential difference was estimated at -1.1 mV. a potential which, in a negatively charge membrane, will also constitute the net driving force for the fluid transfer; this force will be close to, but not identical with, that calculated as conventional from the Starling forces of, in the present case, 23.9 mmHg.61 In the present analysis the distribution of charges in the fluid of the pore resulting from charged groups fixed to the rim of the pore is also considered.

Animals↗
PubMed1996

Characteristics of the glomerular capillary membrane of the rat kidney as a hydrated gel. II. On the validity of the model.

In our gel model applied to the glomerulus, maintenance of membrane integrity is assumed to be preserved not by rigid elements but by the electro-osmotic and balancing hydrostatic pressure offered by negative, fixed charges such that the membrane is able to withstand the external colloid osmotic and hydrostatic forces. Ir a previous study we used micropuncture data to estimate the charge densities required to fulfil this assumption. In the present study the validity of the model was examined from the transport of neutral and negative charged myoglobin as derived from their concentrations in renal venous blood. In order to determine the size of the pores, or rather meshes in the network, the venous concentration of [51Cr]EDTA was also analysed. Based on the ratio between EDTA and neutral myoglobin of 1.08 +/- 0.010 (mean +/- SE, n = 9), the equivalent pore radius was calculated to be approximately 40 A. The ratio of neutral to negative myoglobin in the two series performed was found to be 0.96 +/- 0.018 (n = 8) and 0.97 +/- 0.05 (n = 7), figures which were the same as ratio of 0.97 predicted on theoretical grounds. It is concluded that the experimental data support the hypotheses, although they may also be adapted to the transport in a homogeneously charged membrane; the charge density in this case was estimated at 2.3 mEq L-1. Assuming that the membrane constitutes a network with quadratic meshes, each fibre would seem to carry binding sites approximately 80 A apart and where, in between these binding sites, each fibre was calculated to carry three charges such that the mesh will thus be surrounded by 12 charges.

Animals↗
PubMed1996

The adrenal glands as suppliers of plasma L-Dopa and sources of urinary dopamine.

Dopamine (DA) is a natriuretic hormone synthesized in the kidneys by conversion of filtered 3,4-dihydroxyphenylalanine (L-Dopa), and is activated during hypervolaemia and increased dietary sodium intake. The natriuretic activity of endogenous DA is controversial, however, and the regulation of renal DA synthesis has yet to be explained. It has been suggest that the adrenals may be major suppliers of plasma L-Dopa on the basis of their catecholamine biosynthesis. A study was conducted in rats to elucidate the role of the adrenal glands as dynamic suppliers of L-Dopa to plasma, and thereby as sources of urinary DA. Adrenal venous and systemic arterial plasma concentrations and urinary excretion of L-Dopa, DA and sodium were measured before and during acute isotonic volume expansion (VE; 5% of body weight). One group of animals were acutely adrenalectomized (ADX group) to elucidate the ultimate importance of the adrenals in VE-induced renal sodium and DA excretion. In intact animals, the L-Dopa concentration was 62% higher in adrenal venous than in systemic arterial plasma under control conditions, and 42% higher during VE. The adrenaline concentration was 65 times higher in adrenal venous than in systemic arterial plasma before VE and 56 times higher during VE. The L-Dopa concentration in systemic arterial plasma and the urinary L-Dopa excretion were similar in intact and ADX animals. In intact animals, renal sodium and DA excretion during VE increased more than 13-fold and by 42%, respectively. The corresponding values in ADX animals did not differ from those in the intact animals (more than 14-fold and 36%, respectively). It is concluded that the adrenal glands are only minor suppliers of plasma L-Dopa and minor sources of urinary DA. The regulation of plasma L-Dopa remains to be explained.

Adrenal Glands↗
PubMed1995

Human dentine as a hydrogel.

The pores (tubules) of human dentine in 0.02-cm planoparallel sections of newly extracted permanent teeth were investigated. By the conventional scanning electron microscopy these pores appear empty, but by the newly developed scanning-probe microscopy the presence of a complex matrix could be established. By measuring the transport of neutral myoglobin by diffusion alone and diffusion+bulk flow, the area of dentine occupied by the matrix was calculated to be 1.9 +/- 0.9% and 2.3 +/- 0.5%, respectively. The hydraulic conductivity was surprisingly small, 1.35 +/- 0.55 x 10(-7) ml/(s.cm2 dentine) at a pressure difference of 0.1 kPa across a 1-cm thick section. This suggests a hydrogel with a relatively dense network, the width of meshes estimated at 2 x 30 nm. In line with this concept, enzymatic degradation of the organic matter increased the hydraulic conductivity 3000 times. By studying the transport of negatively charged myoglobin, the matrix was calculated to carry 18 mEq/l of positive charges. Due to the consequent attraction of small, negative ions and thence of water, the pressure within the matrix would be about 1.33 kPa, a force which will act to immobilize the water in the channels. The concept of a hydrogel in the dentine tubules was also supported by the finding that shielding the charges with bathing media of high ionic strength reduced the hydraulic conductivity.

Adolescent↗
PubMed1994

Bikunin in rat plasma, lymph and bile.

Bikunin is a protease inhibitor consisting of a 16 kDa polypeptide and an 8 kDa chondroitin sulphate chain which has an apparent molecular mass of 60-70 kDa upon gel filtration. It is synthesized by hepatocytes and occurs in plasma, both in free form, and in complex with other polypeptides--mainly as the 180 kDa protein inter-alpha-inhibitor. Bikunin binds to proteases less avidly than other plasma inhibitors, making its role in the blood unclear. However, some observations indicate that bikunin has important functions outside the blood system. To assess its capacity to reach extravascular spaces, we have determined the total concentration of bikunin in plasma (0.17 mg/ml), lymph (31 micrograms/ml) and bile (0.2 microgram/ml). Quantitation after removal of complexed bikunin (inter-alpha-inhibitor) by acid precipitation showed that the concentration of free bikunin in those fluids was 3, 1.4 and 0.05 micrograms/ml, respectively. These values yield a lymph/plasma ratio of free bikunin of 0.5, which is higher than expected for a protein of the hydrodynamic size and charge of bikunin. The bile/plasma ratio (0.02), however, is similar to that of other proteins of comparable size. The corresponding values for inter-alpha-inhibitor, 0.16 and 0.001, respectively, indicate that its capacity to pass through the vascular endothelium is relatively high whereas transfer to bile is restricted. Furthermore, we have found that in a perfusate of an isolated rat liver, the ratio of free to complexed bikunin was 30-40 times higher than in plasma, consistent with previous observations showing that free bikunin is cleared from the blood stream much more rapidly than inter-alpha-inhibitor.

Animals↗
PubMed1993

Charge density of renal interstitium.

The charge density of renal interstitium was analysed from the volume of distribution of negative native albumin as compared with neutralized albumin, labelled with 125I and 131I, respectively. The experiments were conducted by infusing the two probes intravenously at a rate which kept the plasma concentrations stable. The concentration in renal hilar lymph, C(lymph)(t), will then obey the function C(lymph)(t) = C(lymph)(t infinity) (1-exp-Kt), where C(lymph)(t infinity) is the steady state concentration and K the time constant for passage of the tracer through the renal interstitium--the former is dependent on the permeability of the peritubular capillary membrane, whereas the time constant is inversely related to the interstitial distribution volume of the tracers. The lymph-to-plasma concentration ratio (L/P-ratio) of negative, native albumin was found to be lower than that of neutralized albumin, a finding suggesting that the peritubular capillary membrane is negatively charged. Regarding the interstitium, it was calculated from the respective time constants, K, that the interstitium/lymph concentration ratio of negative native albumin was 0.96 +/- 0.06 of that of neutralized albumin. This suggests the presence of negative fixed charges repelling negative native albumin. However, since the calculated charge density of -1.8 +/- 1.2 mEq l-1 was not significantly different from zero, it is concluded that the renal interstitium is uncharged. This does not, however, rule out the possibility that, for example, negative groups are fixed to the interstitial matrix, merely that the average fixed charge density of renal interstitial fluid is negligible.

Albumins↗
PubMed1992

Osmotic diuretics and hemodilution in postischemic renal failure.

In the acute phase of ischemic renal failure, the severe depression of the glomerular filtration rate (GFR) is due to obstruction of the tubules by cells and cell debris rejected from the proximal tubules, a blockade which can be prevented at least partly, by treatment with osmotic diuretics. The isosthenuria, the second typical sign in ischemic acute renal failure, probably derives from the medullary ischemia that results from an intracapillary trapping of red cells. This, in turn, is suggested to be caused by oxygen-derived free radicals, which via increasing the capillary macromolecular permeability result in a massive extravasation of plasma and hence in hemoconcentration. As expected from this hypothesis, scavengers may ameliorate both the trapping and the consequent medullary ischemia. Unfortunately, however, a therapy using both osmotic diuretics and scavengers fails to improve the long-term outcome. Hemodilution would seem more promising, since it will both prevent the medullary ischemia seen in the acute phase and substantially improve the long-term outcome. At a hematocrit of 0.30, rat kidneys exposed to 45-min ischemia will show a GFR 1 month after the insult of more than 50% of the normal GFR as against 15% in untreated animals.

Acute Kidney Injury↗
PubMed1991

Oxygen radicals in postischaemic damages in the kidney.

Oxygen radicals in postischaemic damages in the kidney: M. Wolgast, A. Bayati, O. Hellberg, O. Källskog, K. Nygren and G. Ojteg, Inst. of Physiology and Medical Biophysics, University of Uppsala, Sweden; Ischemic acute renal failure is characterized by a severe depression of the glomerular filtration rate (GFR), isosthenuria and deficient potassium secretion, whereas the total renal blood flow may remain largely intact. As to these symptoms, it would seem established that the depression of GFR results from an ischaemia-induced augmented aging and hence rejection of tubular cells, which thence blocks the tubular lumen. As expected this blockade can be prevented by osmotic diuretics. The isosthenuria and the deficient potassium excretion, on the other hand, results probably from a medullary ischaemia, the latter due to the action by oxygen-derived free radicals in the sense the subsequent damage to the capillary membrane leads to a massive extravasation of plasma and consequent intracapillary trapping of red cells. In line with this idea, superoxide-dismutase (SOD) or Allopurinol may ameliorate these changes. In the recovery phase of postischaemic renal failure, the most prominent feature is the blocking of the ascending loop of Henle with Tamm/Horsfall-protein which, if not washed-out during the first week, leads to a complete degeneration of the nephron. Unfortunately, the process would seem to be unaffected by treatment with e.g. osmotic diuretics and SOD or Allopurinol.

Acute Kidney Injury↗
PubMed1991

Red cell trapping and postischemic renal blood flow. Differences between the cortex, outer and inner medulla.

The distribution of blood flow in the rat kidney after 60 minutes of renal ischemia was studied by single-fiber laser-Doppler flowmetry. Blood flow in superficial cortex and inner medulla was measured with a probe directed towards the kidney surface and exposed papilla, respectively. Outer medullary blood flow was measured with a probe introduced through the renal core. After ischemia the blood flow decreased to 60% of the preischemic value (P less than 0.01) in superficial cortex and to 16% (P less than 0.01) in outer medulla, while inner medullary blood flow increased paradoxically to 125% (P less than 0.01). There was extensive trapping of red blood cells (RBC) in the outer medulla, but not in the inner medulla or cortex. The fractional RBC volume as measured by radiolabeled RBCs was 21% in the inner stripe of the outer medulla, but 2% in this area in a normal kidney. To investigate the influence of RBC trapping on intrarenal distribution of blood flow after ischemia, the hematocrit was reduced from 46% to 31% by isovolemic hemodilution. When performed before ischemia, this maneuver almost completely abolished RBC trapping. In this group blood flow in both outer and inner medulla was almost unchanged after ischemia, while superficial cortical blood flow decreased to 66% (P less than 0.01) of the pre-ischemic value. It is concluded that RBC trapping in the outer medulla causes a large decrease in blood flow in this area and, at the same time, shunting of blood to the inner medulla. In the absence of RBC trapping, blood flow of both outer and inner medulla is well preserved after ischemia.

Animals↗
PubMed1990

Red cell trapping after ischemia and long-term kidney damage. Influence of hematocrit.

The influence of the hematocrit (Hct) on the trapping of red blood cells (RBC) in the renal microvasculature and its effect on the long-term outcome following unilateral ischemia were investigated in the rat. The results showed that an increase in the duration of ischemia increased the RBC trapping, as measured by 51Cr-labeled erythrocytes, in a dose-dependent manner. At normal Hct (46%) the period of ischemia producing half-maximum RBC trapping was 45 minutes, whereas after hemodilution (Hct = 31%) or hemoconcentration (Hct = 60%) the corresponding periods were 80 and 25 minutes, respectively. Regarding the long-term outcome, 45 minutes of ischemia with a normal Hct was associated with a marked decrease in kidney weight, GFR and urine osmolarity after four weeks of recovery, which could be prevented to a large extent by hemodilution. Conversely, with hemoconcentration there was severe damage after only 25 minutes of ischemia. It is suggested that these long-term effects are attributable to RBC trapping in the microvasculature of the outer medulla, which may cause added ischemia in this area of the kidney. It is also suggested that cortical atrophy is secondary to the medullary injury, and is brought about to avoid extensive water and salt losses.

Animals↗