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Biomedical subjects

M Wolgast

Publications and source records attributed to M Wolgast.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Nephron function in the early phase of ischemic renal failure. Significance of erythrocyte trapping.

Trapping of red blood cells (RBCs) in renal medulla vasculature in postischemic acute renal failure (ARF) was found to depend upon the length of the ischemic period. Thus trapping occurred after 45 minutes but not 25 minutes of ischemia. By prior hemodilution to a hematocrit (hct) of 30%, RBC trapping after 45 minutes of ischemia could be completely prevented. Likewise hemo-concentration (hct = 60%) before 25 minutes of ischemia resulted in extensive RBC trapping. By increasing or decreasing the hct, the contribution of RBC trapping to the functional defects and decrease in renal blood flow that follows minor (25 min) and more substantial (45 min) ischemia was investigated. Renal blood flow (RBF) was measured by microspheres, and vascular and tubular pressure by the micropuncture technique. Glomerular filtration rate (GFR) was estimated from inulin clearance, and tubular function from urine osmolality and sodium and potassium excretion. It was found that postischemic RBF was not correlated to RBC trapping but depended on the length of ischemia. After both 25 and 45 minutes of ischemia tubular obstructions occurred in the proximal tubules and/or loops of Henle, causing an increase in proximal tubular pressure. These obstructions were dependent on the length of ischemia but not on RBC trapping. After hemoconcentration and 25 minutes of ischemia there was an increment in distal tubular pressure, indicating that abundant RBC trapping may contribute to an increase in tubular pressure by compression of medullary tubules and thereby reduce GFR. When the damage was more severe other factors came into play and the contribution of RBC trapping to the decrease in GFR was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Mechanism of erythrocyte trapping in ischaemic acute renal failure.

Forty-five minutes of warm ischaemia and 20 min of recirculation in the rat kidney was found to result in (1) a massive transient extravasation of plasma upon recirculation and (2) an increase in plasma-lymph transport of proteins during the first hours after onset of circulation. This was accompanied by trapping of erythrocytes, as determined with 51Cr-labelled erythrocytes, in the capillaries, mainly in the inner stripe of the outer medulla. At scanning electron microscopy of vibratome sections, the trapping appeared as aggregates of polygonally shaped erythrocytes. It is concluded that 45 min of ischaemia and 20 min of recirculation results in an increase in the permeability of the renal capillaries. This increase leads to extravasation of capillary plasma with consequent local haemoconcentration, causing an increase in vascular resistance and in capillary hydrostatic pressure. This elevated pressure will, in turn, lead to perpetuating extravasation of plasma, further haemoconcentration and so on, eventually resulting in dense packing of polygonal erythrocytes, obstructing the blood flow. It is believed that oxygen-derived free radicals generated in the early recirculation phase contribute to the increase in macromolecular permeability, since the scavenger bovine superoxide dismutase and allopurinol, a xanthine oxidase inhibitor, were found to prevent this unfavourable chain of events.

Acute Kidney Injury↗
PubMed1990

The long-term outcome of post-ischaemic acute renal failure in the rat. I. A functional study after treatment with SOD and sucrose.

The long-term outcome in rat kidneys subjected to 45 min of warm ischaemia with no treatment and after administration of 20 mg superoxide dismutase (SOD) and of SOD combined with 2 ml of a 12% sucrose solution was studied by the micropuncture technique. It was found that, although in the acute phase SOD prevented trapping of erythrocytes in the medullary vasculature and that SOD + sucrose also prevented the formation of tubular obstruction, the long-term results as studied 1 week and 1 month after the primary ischaemic insult were virtually identical. This was due to the formation of new obstructions, during the first week, mainly in the thick ascending limb of Henle's loop. After 1 month the proximal tubular free-flow pressure and the single-nephron filtration rate had returned to normal. However, since the total glomerular filtration was only one-third of that under normal conditions, it would seem that two-thirds of the nephrons had undergone complete degeneration. This degeneration was probably the result of persistent tubular obstruction. The tubular degeneration was also accompanied by a reduction in urine osmolality and potassium secretion.

Acute Kidney Injury↗
PubMed1990

The long-term outcome of post-ischaemic acute renal failure in the rat. II. A histopathological study of the untreated kidney.

Histopathological changes in kidneys subjected to 45 min of isothermic unilateral ischaemia in the acute phase and 1 week and 1 month after primary damage were studied at the electron microscopic level. During the first week after recirculation long homogeneous cylinders, probably consisting of Tamm-Horsfall protein, developed in the medullary parts of the nephron, and after 1 month of recirculation there were two types of nephrons: (1) nephrons with a normal histological appearance and (2) degenerated nephrons. The latter group gave rise to crypts in the outer cortical area. It is hypothesized that the generation of the long Tamm-Horsfall cylinders in the thick ascending limb of the loop of Henle plays an important role in the long-term outcome of the kidney after the primary damage. The persistent blockade caused by these cylinders will lead to precipitation of the ultrafiltrate, resulting in long cell-protein cylinders in the proximal parts of the nephron. This precipitation will proceed in the retrograde direction, reaching the mother glomeruli, eventually leading to total degeneration of the nephron.

Acute Kidney Injury↗
PubMed1990

The effect of loop diuretics on the long-term outcome of post-ischaemic acute renal failure in the rat.

The effects of continuous treatment with loop-acting diuretics on the long-term functional and histopathological outcome in kidneys subjected to 45 min of warm ischaemia were studied. One month after the primary damage the inulin clearance in the untreated kidneys was 0.44 +/- 0.05 ml min-1, improving significantly to 0.69 +/- 0.11 ml min-1 in furosemide-treated animals and to 0.75 +/- 0.09 ml min-1 in those treated with piretanide. Urine osmolality increased from 986 +/- 89 mosmol kg-1 in the untreated animals to 1479 +/- 195 mosmol kg-1 in the furosemide-treated ones. At the same time the total area of the outer medulla occupied by Tamm-Horsfall protein cylinders decreased from 7.0 +/- 1.2% in the untreated animals to 3.6 +/- 0.52% in the treated ones. It is concluded that by decreasing the number of nephrons blocked by Tamm-Horsfall cylinders an improvement in the function of ischaemically damaged kidneys can be achieved. This blockade, also called secondary damage, is of critical prognostic importance for the long-term outcome of the ischaemic renal failure. Treatment of the animals with loop diuretics decreased the occurrence of these cylinders, leading to an improvement of kidney function I month after the primary damage, this despite the fact that the primary damage seen in the early recirculation period was not treated specifically.

Acute Kidney Injury↗
PubMed1990

Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils.

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.

Animals↗
PubMed1989

The net electric charge of proteins. A comparison of determinations by Donnan potential measurements and by gel electrophoresis.

We compare a new method for the determination of the net charge of proteins based on Donnan potential measurements, as described briefly by Ojteg, G., Nygren, K. and Wolgast, M. (1987) Acta Physiol. Scand. 129, 277-286, with a conventional method using polyacrylamide gel electrophoresis. The new technique utilizes the Donnan potential, which develops over a semipermeable membrane that separates the non-permeating protein from the surrounding bath of the same ionic composition as the protein solution, to determine the net valency. The advantages of this method, besides its simplicity, are that it can determine the charge of, e.g., a protein in a free-fluid phase and that the pH and ionic composition of the bathing fluid can be varied over a broad range. The Donnan potential decreased to half its original value when the ionic strength was doubled. Usually a protein concentration of 1-10 mg.ml-1 must be used. The Donnan potential method was applied to determine the net charges of a series of proteins with different isoelectric points. The values showed close agreement with the data obtained by gel electrophoresis.

Animals↗
PubMed1988

Extensive tubular secretion and reabsorption of creatinine in humans.

The validity of creatinine as a marker for the glomerular filtration rate was studied in 8 healthy volunteers in different stages of hydration and during large variations in urinary flow rates. The urine flow was 8.4 ml/min in a dehydrated state (due to furosemide infusion; 8 mg/h) and raised to 23.2 ml/min after rapid rehydration. The creatinine to inulin clearance ratio changed considerably from 1.47 in rehydrated state, indicating a substantial tubular secretion of creatinine, to 1.05 in dehydrated state, indicating a reabsorption of creatinine almost equal to secretion. Thus, substantial tubular secretion and reabsorption of creatinine, changing in relative importance in relation to the degree of hydration, make creatinine clearance an unreliable marker for the glomerular filtration rate.

Blood Urea Nitrogen↗