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B Agerup

Publications and source records attributed to B Agerup.

17 recordsLinked to original sources

Enhanced uptake of actinomycin D in the dog kidney by simultaneous injection of degradable starch microspheres into the renal artery.

Tritiated Actinomycin D and degradable starch microspheres were simultaneously injected into a renal artery in dogs. The spheres functioned to mechanically retard the washout of the drug from the kidney microcirculation. Degradation of the spheres by endogenous amylase resulted in the reestablishment of normal kidney blood flow within an hour after injection. Twenty-three per cent of the total amount of drug injected was retained in the kidney one hour after injection of the drug-sphere combination. When the same amount of the drug alone was selectively injected into a renal artery or given intravenously, 9% and 1.3% of the injected dose, respectively, was found in the kidney tissue one hour after injection. This procedure may be of benefit in the treatment of solid tumors, where the therapeutic ratio may be increased because of higher drug retention in the tumor tissue with a decreased availability of the drug for other sensitive tissues.

Animals↗

Modulation of proximal tubular hydraulic conductivity by peritubular capillary oncotic pressure.

Fluid absorption from the proximal tubular lumen is probably a multifactorial process. Earlier studies from our laboratory have indicated that a transepithelial hydrostatic and oncotic pressure difference may be the driving force for as much as 30% of the reabsorbed fluid. During saline volume expansion proximal tubular reabsorption declines and the present experiments were undertaken to investigate whether this reduction could be caused by changes in the passively driven flux component. The hydraulic conductivity was therefore determined from the reabsorptive rate in split oil droplets with normal and high hydrostatic pressure gradients across the wall, at the same time as the peritubular capillary net-work was perfused with solutions containing a colloid of high or low concentration. In the reabsorption experiments the split oil droplet radius was measured and in a separate series of experiments the relationship between droplet radius and pressure was determined; this was found to be 7.3 mmHg pressure increase per 1 micrometer increase in radius. The increase in the rate of reabsorption from the droplets due to increased intraluminal hydrostatic pressure was 1.02 +/- 0.13 nl/min/mm tubular length when a solution with a high colloid concentration was perfused through the capillary net-work, compared with 0.41=0.11 nl/min/mm tubular length when a low colloid containing solution was used for perfusion. The hydraulic conductance in the proximal tubular wall at high colloid perfusion was calculated to be 0.54 nl/min.mm.mmHg while at a low capillary colloid oncotic pressure it was significantly lower 0.025 nl/min.mm.mmHg. This drop in hydraulic conductance might be one factor responsible for the decline in fluid absorption in animals exposed to saline volume expansion.

Animals↗

Quantification of the inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A methodological study.

An experimental model for studying the early healing of open wounds in the rat is described. With this model, exudate is easily collected, a standardized granulation tissue is achieved at different post-wounding time intervals and local treatment of the wounds is possible. The model involves the use of stainless steel rings with covers, fastened to the edges of two circular full-thickness open wounds, one on each side of the animal's back in the thoracic region. Blood flow and water content of the granulation tissue were determined acutely 3, 5, 7 and 10 days after wounding. The collagen accumulation in the granulation tissue was assessed by the amount of hydroxyproline, at the same time intervals. The amount of exudate which accumulated in the chamber was measured daily. Blood flow in the granulation tissue, as measured by radioactive microspheres, reached a maximum of 947 ml X min-1 X (100 g dry weight)-1 7 days after wounding. The water content, as assessed by freeze-drying, also reached its peak on the 7th day (5.5 ml X (g dry weight)-1). Changes in water content were found to be due to changes in interstitial fluid volume, as studied by 59Fe-labelled erythrocytes and 51Cr-EDTA. The amount of hydroxyproline in the granulation tissue increased from 22 micrograms X (mg dry weight)-1 on day 3 to 37 micrograms X (mg dry weight)-1 on day 10. Exudation increased to 28 microliters X h-1 X cm2-1 on day 4 and then declined. The results suggest that the inflammatory reaction, expressed as alterations in blood flow and water content, reaches a maximum on day 7 after wounding. The data also demonstrate a continuous increase in the collagen content of the granulation tissue during the 10-day period of observation. In addition, exudation was found to reach a peak on the 4th to 5th day, and then declined.

Animals↗

A new principle for prevention of diarrhoea caused by enterotoxigenic Escherichia coli (ETEC) possessing colonization factor antigen (CFA/I).

The infant rabbit model, developed to study human ETEC with CFA/I (Evans et al., 1975), was used to evaluate agarose (Sepharose) gel substituted with a hydrophobic ligand for prevention of diarrhoeal symptoms. In a group of rabbits given 0.02 g of palmitoyl Sepharose 1 h after an oral infection with 10(9) ETEC organisms with CFA/I antigen, only 2/11 animals developed diarrhoea, while in control groups given the unsubstituted Sepharose (hydrophilic) gel or ETEC organisms alone, all animals developed diarrhoea. In groups of rabbit given the hydrophobic gel 6 h after the ETEC organisms, only 2/6 animals showed a short period of diarrhoea. The "hydrophobic principle" to prevent ETEC infections will be studied in other animal models and in human volunteers.

Animals↗

Renal proximal tubular acidification. Role of brush-border and cytoplasmic carbonic anhydrase.

Carbonic anhydrase is found in the cytoplasm and brush border membranes of renal proximal tubular cells. Both the soluble and the membrane-bound enzyme have been assigned roles for the secretion of hydrogen ions into the tubular fluid and hence also for the reabsorption of bicarbonate. Attempts were made to differentiate between the roles of these enzymes for the rate of proximal tubular acidification. Proximal tubules of rats were instilled and perfused with bicarbonate solutions containing carbonic anhydrase inhibitors, especially designed to be impermeable to cell membranes. The acidification rate was measured with an antimony micro-electrode system--the only instantly responding micro-pH electrode. The membrane impermeable inhibitors had no effect on this rate in contrast to acetazolamide, which markedly inhibited the acidification rate when administered intraluminally. It is therefore concluded that the cytoplasmic carbonic anhydrase is the important enzyme for the proximal tubular acidification rate, and hence the rate of bicarbonate reabsorption. The function of the brush border enzyme remains an outstanding problem.

Acetazolamide↗

[beta2-Microglobulin in cancer patients (author's transl)].

Cancerembryonic antigen (CEA) and beta2-microglobulin (beta2m) have been measured in cancer patients and patients with benign diseases. Of 168 patients with intestinal cancer, almost 90% had increasing concentrations of either CEA or beta2m or both. In 29 patients at different stages of pancreatic cancer there was a high incidence of increased values in the more severe cases. In 60 patients with histologically classified colorectal cancer the TNomegaMomega group of 19 patients had 47% and 42% of elevated beta2m and CEA respectively. A significant correlation of beta2m or CEA to extension of disease was noted. In benign intestinal disease like cirrhosis and pancreatitis both beta2m and CEA is commonly elevated. Of 26 breast cancer patients, seven had elevated CEA and five had elevated beta2m values before treatment. In the patients with extraganglionary metastasis almost 90% had high beta2m or CEA or both. Of 40 patients with uterine cancer, 26 were found to have increased values of beta2m or CEA or both. Finally, 140 colorectal cancer patients, 62 patients with breast cancer and 10 patients with uterine cancer have been followed longitudinally.

Beta-Globulins↗

The hydraulic conductivity of the rat proximal tubular wall determined with colloidal solutions.

The hydraulic conductivity of the rat proximal tubular wall was determined using colloidal solutions perfused in short (50--200 mum) (SMP) or long (90--200 mum) (LMP) proximal tubular segments. In SMP human serum albumin (HSA) or polyvinylpyrrolidone (PVP) was added to raffinose solutions. A Lp of 0.019 nl-min-1-mm-1-mm Hg-1 was found when high colloid concentrations were used while values of 0.055--0.092 were found when low colloid concentrations were used. In other experiments, the Lp was determined by perfusing short tubular segments with pure raffinose solutions. A value of 0.015 nl-min-1-mm-1-mm Hg-1 was found. This is twice the value found when raffinose solutions were perfused through long tubular segments and it is concluded that the short microperfusion technique overestimates Lp with a factor of two. When microperfusions of long tubular segments were conducted, PVP was added to an equilibrium solution consisting of NaCl (110 mM) and raffinose (80 mM). Lp was found to be 0.018--0.021 when high colloid concentrations were used, while a value of 0.029 was found when a low colloid concentration was used. As found in both SMP and LMP a decrease in Lp's with increasing colloid concentrations indicates that a significant influence of radial concentration differences is highly probable. It is therefore suggested that the highest Lp derived when using the lowest colloid concentrations represents the best estimate. With this Lp value (0.03--0.05 nl-min-1-mm-1-mm Hg-1) and the existing transtubular hydrostatic and oncotic pressure difference it can be calculated that these passive forces might constitute the driving force for 1/3 of the fluid reabsorbed in the proximal tubule.

Animals↗

Influence of peritubular hydrostatic and oncotic pressures on fluid reabsorption in proximal tubules of the rat kidney.

Proximal tubular reabsorption was measured with the split droplet technique under the following conditions. Group 1. Star vessel perfusions with ultrafiltrate in the presence of human serum albumin (HSA) and with ultrafiltrate alone. Group 2. Capillary perfusions, under locally high flow rates, with ultrafiltrate in the absence or presence of HSA. Group 3. Subcapsular perfusions with ultrafiltrate of high HSA concentrations but under low hydrostatic pressure and ultrafiltrate of low HSA concentrations but under elevated hydrostatic pressure. In Group 1, the presence of HSA increased the reabsorptive rate, whereas ultrafiltrate alone had no provable effect on the reabsorptive rate. In Group 2, a flow dependent decrease of the reabsorptive rate, that was not influenced by the presence of HSA, was observed. Finally, in Group 3, high concentrations of HSA did not alter the reabsorptive rate, whereas elevation of the hydrostatic pressure decreased the reabsorptive rate. The results cannot be explained on the basis of a simple passive mode of action of colloid osmotic and hydrostatic pressure on the reabsorptive rate. The possibility of a direct tubulae capillary transport route is discussed.

Animals↗

Tubuloglomerular feedback. Nonlinear relation between glomerular hydrostatic pressure and loop of henle perfusion rate.

The present experiments were performed to quantify the effect of changes in distal tubular sodium delivery on glomerular flow dynamics both below and above the normal physiologic range. Glomerular capillary pressure as derived from the tubular stop flow pressure was assessed while the loop of Henle of the same nephron was perfused with varying flow rates. During Ringer perfusion no change of glomerular capillary pressure was observed when flow was increased from 0 to 13 nl/min. Further increasing flow to 27 nl/min was associated with a reduction of glomerular hydrostatic pressure by an average of 7.0+/-4.4 cm H(2)O (+/-SD). During perfusion at a rate of 43 nl/min glomerular pressure was decreased by a mean of 10.5+/-4.0 cm H(2)O. Changing the flow rate in small steps revealed that a significant reduction of capillary pressure was found when increasing the flow rate from 13 to 21 nl/min and that the maximum response was reached at 32 nl/min. No effect of perfusion rate changes on glomerular capillary pressure was observed when 300 mM mannitol was used as perfusion fluid. These results imply that a nonlinear relationship exists between end-proximal flow rate and glomerular capillary pressure. It is suggested that during deviations of distal sodium delivery into a positive direction filtration rate is intrarenally regulated probably by prevalence of afferent arteriolar constriction. During reductions of distal sodium load intrarenal regulation is either abolished or it involves proportionate resistance changes of both afferent and efferent arterioles.

Animals↗

Glycerol effects on the perilymphatic and cerebro-spinal fluid pressure.

Glycerol has been injected intravenously in guinea pig and its effects on the pressure in the cochlear fluids have been studied. Simultaneously, arterial and cerebro-spinal pressures have been recorded. Glycerol lowered the intracochlear as well as cerebro-spinal and blood pressures, the latter only temporarily. Different possible mechanisms for the glycerol effect on the intracochlear pressure and its transient effect on hearing in Menière's disease are discussed.

Animals↗

The cochlear blood flow.

Cochlear blood flow in the guinea pig was investigated using Tracer Sephadex 15 microspheres labelled with radioactive nuclides. A reference organ technique was used for quantitative measurements of cardiac output and the blood flow in the cochlear soft tissue, CNS and kidney. In some experiments the blood flow was measured at two occasions, either with 57Coor with 58Co-labelled microspheres. The results, including the size of cochlear blood flow are presented and discussed.

Animals↗