"The Phoenix": 70 years of publishing.
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Anatomy, Artistic↗
Biomedical subjects
P Hansell
Publications and source records attributed to P Hansell.
Renomedullary interstitial cells regulate hyaluronan turnover depending on growth media osmolality suggesting a role in renal water handling.
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Animals↗
Hypoperfusion in the renal outer medulla after injection of contrast media in rats.
PURPOSE: The effect on regional renal blood was studied after injection of nonionic iso-osmolar iotrolan or ionic high-osmolar iothalamate. MATERIAL AND METHODS: Laser-Doppler flowmetry was used to measure outer medullary (OMBF) and superficial cortical blood flow (CBF) simultaneously in anesthetized rats. Iotrolan (320 mOsm/kg H2O) was injected i.v. at a dose of 600 mg I/kg b.w. (normal dose) over 2 min or 1,600 (high dose) mg I/kg b.w. over 2 or 8 min. Iothalamate (2,580 mOsm/kg H2O) was injected i.v. at a dose of 1,600 (high dose) or 2,900 (extremely high dose) mg I/kg b.w. over 2 min. RESULTS: At the normal dose and 2-min injection of iotrolan, OMBF was reduced by 25+/-9% over 20 min. The high dose of iotrolan injected over 8 min resulted in a reduction in OMBF slightly smaller (17+/-9%) than that induced by the normal dose but lasting longer (30 min). Compared to the normal dose, the high dose and fast (2 min) injection of iotrolan resulted in a greater and more prolonged decrease in OMBF (32+/-6% lasting 50 min). After the high dose of iothalamate (1,600 mg I/kg) there was a decrease in OMBF by 21+/-6%, lasting 30 min. An extremely high dose (2,900 mg I/kg b.w.) gave a heterogeneous response with a mean increase in OMBF of 48+/-24% occurring 60 min after the injection. CONCLUSION: Iso-osmolar and high-osmolar contrast media (CM), at normal and high doses, decrease OMBF, while an extremely high dose of iothalamate may result in an increase. The depression of outer medullary perfusion may have implications for CM-induced acute renal failure in view of the vulnerability of this region to a decrease in oxygen tension.
Animals↗
Influence of iotrolan on renal cortical and outer medullary blood flow in the rat.
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Animals↗
Different renal effects of two inhibitors of catechol-O-methylation in the rat: entacapone and CGP 28014.
Dopamine is a natriuretic hormone that is abundantly synthesized in the kidney and is involved in sodium homeostasis. It is metabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) to form 3-methoxytyramine and dihydroxyphenylacetic acid (DOPAC) and finally homovanillic acid (HVA). In order to investigate whether dopamine metabolism is involved in renal sodium regulation, we tested the renal effects of the nitrocatechol entacapone (COMT inhibitor), in comparison with those of the pyridine derivative CGP 28014, in the anaesthetized rat. Entacapone injection resulted in a more than 5-fold increase in sodium excretion, while the renal excretion of dopamine only transiently increased by 20%. DOPAC excretion showed a more than 2-fold increase which persisted throughout the study. Pretreatment with the selective dopamine DA1-receptor antagonist SCH23390 reduced the entacapone-induced natriuretic response by 69%. Glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) remained unchanged. Injection of CGP 28014 did not produce a natriuretic response; nevertheless, both dopamine and DOPAC excretion increased by 78% and more than 2-fold, respectively. GFR and MAP remained unchanged. In conclusion, COMT inhibition using entacapone results in a mainly DA1 receptor mediated natriuresis involving inhibition of tubular transport processes, supporting a role for dopamine metabolism in sodium homeostasis. Although CGP 28014 increases the renal excretion of both dopamine and DOPAC it does not affect renal sodium handling indicating a different mechanism of action.
Amidines↗
Leukocyte adhesion in angiogenic blood vessels. Role of E-selectin, P-selectin, and beta2 integrin in lymphotoxin-mediated leukocyte recruitment in tumor microvessels.
Interaction of circulating leukocytes with tumor microvasculature is a critical event in the recruitment of effector cells into the tumor stroma. We have examined the ability of lymphotoxin (TNF-beta), to stimulate rolling, adhesion, and transmigration of leukocytes in angiogenic blood vessels induced by tumor spheroids of Lewis lung carcinoma (LLC) implanted in dorsal skinfold chambers of nude mice. In the absence of cytokine stimulation, circulating leukocytes failed to appreciably interact with tumor microvessels (TMV), although significant rolling and adhesion was observed in normal vessels. However, stimulation with lymphotoxin (LT) resulted in a rapid increase in the number of fast and slow rolling leukocytes in TMV. Treatment with anti-P-selectin mAb 5H1 resulted in inhibition of fast rollers alone, while combination treatment with anti-P-selectin and anti-E-selectin (9A9) mAbs effectively blocked slow rolling of leukocytes. Superfusion of the lymphotoxin-stimulated neovasculature with leukotriene B4 (LTB4) resulted in stable cell adhesion followed by emigration of leukocytes into the tumor stroma. LTB4-mediated adhesion and transmigration was significantly inhibited by treatment with anti-beta2 mAb 2E6. These studies delineate a multistep cascade of leukocyte adhesion in TMV and demonstrate that stimulation of the neovasculature with cytokines and chemoattractants can result in P- and E-selectin-dependent rolling and beta2-dependent stable adhesion followed by transmigration into the tumor stroma.
Animals↗
Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique.
The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.
Adult↗
Thomas Albert Longmore, Hon FSR, FRPS (1905-1957).
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England↗
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↗
Differences in binding of platelet factor 4 to vascular endothelium in vivo and endothelial cells in vitro.
The binding of fluorescein-labelled recombinant human platelet factor 4 (rhPF4) to the vasculature of the hamster cheek pouch in vivo was compared with that to cultured endothelial cells (EC) from human umbilical veins (HUVEC) and arteries (HUAEC) and from human aorta (HAEC). In vivo data: systemically injected rhPF4 rapidly disappeared from plasma in a biphasic pattern (t1/2 = 2 and 41 min). High intensity non-uniform binding of rhPF4 occurred at short specific sites along both arterioles and venules. The length of the intense sites was 76 +/- 46 microns and their frequency was 10 +/- 4 per cm2 cheek pouch. Heparin was injected at 4 and 9 min, but not 30 min, post-rhPF4 displaced most of the high intensity labelling indicating internalization with time. Neither pretreatment with more than 50-fold excess of unlabelled rhPF4 nor histamine- or LTB4-induced vascular macromolecular leakage changed the frequency of short intense sites. In vitro data: uniform time-dependent intense binding of rhPF4 occurred in a similar fashion in subconfluent HUVEC, HUAEC and HAEC. All cell types showed nuclear staining, demonstrating internalization. When heparin was given to EC prior to rhPF4, binding was delayed in time but not blocked. In conclusion, rhPF4 does not bind uniformly with high intensity along pre- and post-capillary vessels of the hamster cheek pouch in vivo as predicted by the rhPF4-labelling of subconfluent (migrating/proliferating) human EC in vitro. The short infrequent sites of intense rhPF4-labeling in vivo may represent regions of endothelial cell migration/proliferation similar to subconfluent EC in culture.
Animals↗
Sodium and dopamine excretion in prehypertensive Dahl rats during severe hypervolaemia.
As opposed to the salt-resistant Dahl-R rat the salt-sensitive Dahl-S has a defective renal dopamine DA1 receptor that may be involved in its susceptibility to develop hypertension during a high salt diet. To compare the ability of prehypertensive Dahl-R and Dahl-S to respond to a severe isotonic sodium load, renal function was monitored during a severe form of acute isotonic volume expansion (10% VE). Mean arterial blood pressure before VE was similar in Dahl-R and Dahl-S and decreased in both strains by 6% during VE. The accumulated sodium excretion during VE in Dahl-R was 411 +/- 64 micromol 100 min(-1) g(-1) kidney wt (kw) which was not different from that in Dahl-S (420 +/- 95 micromol 100 min(-1) g(-1) kw). The accumulated dopamine excretion (a mirror of renal dopamine synthesis) during VE was also similar in Dahl-R (134 +/- 13 ng 100 min(-1) g(-1) kw) and Dahl-S (126 +/- 16 ng 100 min(-1) g(-1) kw). The excretion of DOPAC, the main metabolite of Dahl-S, glomerular filtration rate and systemic haematocrit did not differ between the strains before, during or after VE. To conclude, in spite of a defective renal DA1 receptor prehypertensive Dahl-S do not respond with an attenuated natriuretic or dopamine excretory response when subjected to a severe isotonic sodium load. The results do not support a sodium retaining role over a defective DA1 receptor in the salt-sensitive hypertension in Dahl-S.
3,4-Dihydroxyphenylacetic Acid↗
Selective binding of platelet factor 4 to regions of active angiogenesis in vivo.
In a previous study we suggested that recombinant human platelet factor 4 (rhPF4) preferentially binds in vivo to regions of active angiogenesis/endothelial cell migration. To test this hypothesis, binding of fluorescently labeled rhPF4 to newly formed vessels was compared with that of the normal skin vasculature, using syngeneic Langerhans islets as inducers of angiogenesis. Islets were implanted in the dorsal skinfold chamber of the hamster, and the binding of rhPF4 was studied using intravital fluorescence microscopy. Intra-arterially injected rhPF4 labeled, with high intensity, the endothelium along newly formed vessels of the islets (1,632 +/- 617 microns labeled vessel length per islet), and only on rare occasions (1 +/- 2 sites per cm2 skinfold) were short (62 +/- 48 microns) intense-labeled sites found in the normal vasculature of the skinfold. Heparin could displace most of the label if injected within 10 min after the rhPF4 injection, but not 30 min after. In conclusion, rhPF4-preferentially binds to regions of active angiogenesis in vivo. On binding, rhPF4 is internalized as judged from a decreasing heparin sensitivity with time after rhPF4 injection. The infrequent rhPF4-labeling sites in the normal skin vasculature most likely represent regions of newly formed cells/migration, i.e., normal endothelial turnover, supporting our previous findings demonstrating that the occurrence of such regions is rare in the normal microvasculature. Furthermore, despite the previously demonstrated short half-life in plasma, systemically injected rhPF4 will target regions of angiogenesis with high affinity, thereby facilitating the antiangiogenic effect of PF4.
Animals↗
Influence of acridine tracer dyes on neutrophil function.
A study was performed to elucidate the effect of two commonly used fluorescent dyes in in vivo microscopic studies, acridine orange (AO) and acridine red (AR), on the ability of phorbol myristate acetate (PMA)- or formyl peptide (fMLP)-stimulated human neutrophils to adhere to a bovine serum albumin matrix and to generate superoxide anions (SOX). Unlabeled stimulated human neutrophils showed 36 +/- 9% (PMA, 10(-7) M) and 11 +/- 7% (fMLP, 10(-7) M) adherence to the matrix. This adhesion was CD18 dependent as evidence by 98% and 92% reduction, respectively, when the anti-CD18 antibody IB4 was included. A dose-dependent inhibition of stimulated human neutrophil adhesion was evident after 30 min of in vitro dye labeling and the EC50 was approximately 70 micrograms/ml (AR) and 145 micrograms/ml (AO). SOX generation by PMA-stimulated neutrophils was unaffected up to 100 micrograms/ml AR and AO but was reduced by 40-60% at higher doses. Rabbit neutrophils labeled in vivo or in vitro with 100 micrograms/ml AR exhibited 41% and 61% lower SOX generation, respectively. The study indicate that neutrophil function, in terms of ability to adhere to a BSA matrix using CD11/CD18 integrins and to generate SOX upon stimulation, is reduced depending on the dose and choice of fluorescent dye. Caution should be exercised when using these compounds at high concentrations in studies of PMN function.
Acridine Orange↗
Red-cell trapping in the rat renal microcirculation induced by low-osmolar contrast media and mannitol.
RATIONALE AND OBJECTIVES: In acute renal failure after ischemia, intravascular obstruction by trapped red blood cells in the microvasculature of the renal outer medulla is a consistent finding. The influence of intravenously injected contrast media (CM) on such obstruction was investigated. METHODS: Anesthetized rats were subjected to 45 minutes of unilateral renal ischemia. Red-cell trapping in ischemically injured kidneys and in the contralateral uninjured kidneys was estimated from the intrarenal distribution of 51Cr-labelled erythrocytes after injection of ioxaglate or iopamidol in a dose of 1,600 mg I/kg body weight. As an osmolar control substance, mannitol (950 mOsm/kg) was given to a third group and isotonic Ringer's solution was administered to a fourth group. RESULTS: In the uninjured kidneys, treatment with ioxaglate or mannitol resulted in no red-cell trapping, while the iopamidol-treated group showed red-cell trapping in the inner stripe of the outer medulla in a dose-dependent manner. In the ischemically injured kidneys, both CM and mannitol enhanced the red-cell trapping in the inner stripe of the renal medulla. CONCLUSION: The results indicate that intravenously administered ioxaglate and iopamidol enhance the microvascular obstructions evoked by ischemic injury and that iopamidol may induce local impairment in renal medullary microcirculation in a normal kidney.
Animals↗
Pressure-related capillary leukostasis following ischemia-reperfusion and hemorrhagic shock.
Although the receptor-dependent venular adhesion of leukocyte adherence has been relatively well characterized, less is known about capillary leukostasis. With the use of fluorescence intravital microscopy, leukocyte behavior in the capillaries of rabbit tenuissimus muscle was evaluated after ischemia-reperfusion or hemorrhage. After fixed volume hemorrhage or 4 h of total ischemia, inflammatory injury was manifest by broken fibrils, edema, leukocyte infiltration, and margination along the postcapillary venular walls. Nevertheless, as long as arterial perfusion pressure was between 27 and 72 mmHg, the frequency of capillary leukostasis was low (4-8 cells/mm2) and similar in all groups, including animals treated with the antiadhesion antibody IB4. In contrast, when perfusion pressure decreased to 20 mmHg, capillary leukostasis increased similarly (to 16-21 cells/mm2) in controls (with or without IB4) and in those subjected to ischemia. Furthermore, when perfusion pressure was increased to more than 27 mmHg, (27-72 mmHg) stationary leukocytes returned to the original low level (4-5 cells/mm2). These results are consistent with the conclusion that during some inflammatory injuries, capillary leukostasis is a pressure-related phenomena that is not receptor dependent and is freely reversible with the early restoration of perfusion pressure.
Animals↗
Influence of captopril on red cell velocity in the vasa recta of the renal medulla.
Previous studies from our laboratory have indicated an important role for angiotensin II (AII) in the regulation of renal medullary haemodynamics during normal physiological conditions. In order to investigate further the influence of endogenous AII on the juxtamedullary vascular resistance in anaesthetized rats the velocity of fluorescently-labeled red cells (vRBC) was measured with a cross-correlation technique in the vasa recta before and after infusion of the angiotensin I- converting enzyme inhibitor captopril or vehicle. Irrespective of treatment, vRBC was higher in the descending vasa recta (DVR) than in the ascending vasa recta (AVR). In time control animals VRBC in DVR and AVR and mean arterial blood pressure (MAP) remained stable over the 45 min study period. In animals receiving captopril (3 mg.h-1.kg-1 bw) vRBC increased almost proportionally in DVR and AVR; by 26% in DVR (from 1.02 +/- 0.12 to 1.28 +/- 0.10 mm.s-1, p < 0.05) and by 19% in AVR (from 0.46 +/- 0.05 to 0.55 +/- 0.07 mm.s-1, p < 0.05). MAP decreased by 9% (from 107 +/- 3 to 97 +/- 2 mm Hg, p < 0.05). These results give further support to the suggestion of an involvement of AII in the regulation of juxtamedullary vascular resistance during normal physiological conditions.
Angiotensin II↗
Effect of intravenous contrast media on proximal and distal tubular hydrostatic pressure in the rat kidney.
The effect of i.v. injection of contrast media (CM, 1,600 mg I/kg b.w.) on proximal and distal tubular hydrostatic pressure (PTHP, DTHP) in the rat was investigated using a micropuncture technique. The PTHP and DTHP after injection of diatrizoate, iohexol, ioxaglate, or mannitol returned to control values within approximately 20 min. However, following iotrolan injection PTHP was still elevated above control levels after 35 min while DTHP remained elevated throughout the experiment (50 min). Iotrolan has a lower osmotic potential than the other CM when given in equivalent iodine doses. The concentration of iotrolan may thus increase more along the tubules than the other CM and consequently lead to a higher viscosity of urine, resulting in increases in PTHP and DTHP. The high intratubular pressure induced by iotrolan may explain our previous findings of reduced single nephron glomerular filtration rate caused by this CM.
Animals↗