Biomedical subjects

Fredrik Palm

Publications and source records attributed to Fredrik Palm.

9 recordsLinked to original sources

PubMed2005

Thick ascending tubular cells in the loop of Henle: regulation of electrolyte homeostasis.

Renal medullary tubular cells in the loop of Henle have crucial importance for the regulation of homeostasis of the extracellular fluid. These cells receive limited amount of blood and oxygen, and are also constantly challenged by the hypertonic environment. The medullary tubular cells in the last part of the loop of Henle have one of the highest known contents of mitochondria of all mammalian cells, reflecting their need for oxidative metabolism in order to sustain high ATP production for active transepithelial electrolyte transport. The commonly used diureticum furosemide targets one of the transporters present in these tubular cells with resulting diuresis. Several pathological states are associated with altered function of the medullary tubular cells, and the nephrotoxic substances tacrolimus and cyclosporine act on these cells. The specific Tamm-Horsfall glycoprotein is produced by medullary tubular cells. Alteration in the urinary excretion of this protein is used as marker of tubular damage.

Animals↗

PubMed2005

The effects of carbon dioxide versus ioxaglate in the rat kidney.

PURPOSE: The renal medulla seems to be particularly vulnerable to vascular injection of iodinated contrast media, particularly in patients with preexisting renal dysfunction. The gas carbon dioxide is frequently used as an alternative to iodinated contrast medium in these patients. In this study, the renal effects of CO(2) are investigated and compared with those of the iodinated contrast medium ioxaglate. MATERIALS AND METHODS: Cortical and outer medullary blood flow (measured by laser Doppler flowmetry) and oxygen tension (Po(2); measured by oxygen microelectrodes) were recorded in anesthetized Sprague-Dawley rats given an intraarterial injection of ioxaglate (320 mgI/kg body weight), a volume-matched dose of CO(2), or Ringer solution. RESULTS: Injection of CO(2) induced a pronounced and transient decrease in cortical blood flow and Po(2) (approximately -45%), whereas outer medullary blood flow and Po(2) were transiently increased (+21% and +29%, respectively). In contrast, injection of ioxaglate did not influence cortical blood flow and caused outer medullary blood flow to decrease by 17%. Ioxaglate injection also resulted in a decrease in cortical and outer medullary Po(2) (-15% and -33%, respectively). Ringer solution affected none of the recorded parameters. CONCLUSIONS: Although injection of CO(2) markedly affected regional renal blood flow and Po(2), there were qualitatively different effects in the cortex and outer medulla compared with those seen after injection of ioxaglate. The pronounced decrease in medullary blood flow and Po(2) observed after injection of ioxaglate was absent in the animals injected with CO(2). This might suggest beneficial effects of the use of CO(2) instead of iodinated contrast media in patients with increased risk of developing renal failure.

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PubMed2004

Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat.

Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A1-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO2) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A1-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO2 (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and PO2 (-80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO2, urine output and blood pressure was unaffected by the A1-receptor antagonist. Adenosine A1-receptors are not important mediators of the depression of outer medullary blood flow and PO2 caused by the CM iopromide in the normal rat; however, A1-receptors are tonically active to regulate renal haemodynamics, PO2 and urine production during normal physiological conditions.

Adenosine A1 Receptor Antagonists↗

PubMed2004

Promoting islet cell function after transplantation.

Engraftment (i.e., the adaptation of transplanted pancreatic islets to their new surroundings with regard to revascularization, reinnervation, and reorganization of other stromal compartments) is of crucial importance for the survival and function of the endocrine cells. Previous studies suggest that transplantation induces both vascular and stromal dysfunctions in the implanted islets when compared with endogenous islets. Thus the vascular density and the blood perfusion of islet grafts is decreased and accompanied with a capillary hypertension. This leads to hypoxic conditions, with an associated shift toward anaerobic metabolism in grafted islets. An improved engraftment will prevent or compensate for the vascular/stromal dysfunction seen in transplanted islets and thereby augment survival of the islet implant. By such means the number of islets needed to cure the recipient will be lessened. This will increase the number of patients that can be transplanted with the limited material available.

Animals↗

PubMed2003

Effects of the contrast medium iopromide on renal hemodynamics and oxygen tension in the diabetic rat kidney.

UNLABELLED: We investigated the effects of the contrast medium (CM) iopromide on regional renal blood flow and oxygen tension (pO2) in the streptozotocin (STZ)-induced diabetic Wistar Furth rats. RESULTS: In normoglycemic rats, CM injection induced a transient decrease followed by an increase in renal cortical blood flow (CBF), whereas CBF increased directly in the diabetic animals. Renal outer medullary blood flow (OMBF) increased in controls, while it decreased in the diabetic animals following CM injection. In control rats a marked initial decrease in OM pO2 following injection of CM was observed. In animals diabetic for 4 weeks only a slight decrease was seen, whereas in 9-week diabetic animals a persistent increase was recorded. CONCLUSIONS: An altered oxygen tension and hemodynamic response to CM was found in diabetic rats. If these disturbances may contribute to the development of renal dysfunction by CM in the diabetic rat kidney remains to be elucidated.

Animals↗

PubMed2002

pH is decreased in transplanted rat pancreatic islets.

Recent studies of transplanted pancreatic islets have indicated incomplete revascularization. We investigated the pH, in relation to oxygen tension (Po(2)), in endogenous islets and islets syngeneically transplanted to the renal subcapsular site of nondiabetic and streptozotocin-diabetic recipients. Tissue pH and Po(2) were measured using microelectrodes. In the endogenous islets, tissue pH was similar to that in arterial blood. In the transplanted islets, tissue pH was 0.11-0.15 pH units lower. No differences in islet graft pH were seen between nondiabetic and diabetic animals, and none if the islet grafts were investigated 1 day or 1 mo posttransplantation. The Po(2) in the endogenous islets was approximately 35 mmHg. Transplanted islets had a markedly lower tissue Po(2) both 1 day and 1 mo after transplantation. A negative correlation between the tissue Po(2) and the hydrogen ion concentration was seen in the 1-mo-old islet transplants in diabetic animals. In conclusion, decreased Po(2) in transplanted islets is associated with a decreased tissue pH, suggesting a shift toward more anaerobic glucose metabolism after transplantation.

Animals↗

PubMed2002

Oxygen tension in isolated transplanted rat islets and in islets of rat whole-pancreas transplants.

Despite similar immunosuppressive protocols having been applied, the success rate of pancreatic islet transplantation has been much lower than that of whole-pancreas transplantation. We compared the oxygen tension in syngeneically transplanted isolated rat islets and islets of syngeneic rat whole-pancreatic grafts, with native islets, using Clark-type microelectrodes. An oxygen tension of approximately 40 mmHg was recorded in both native islets and in islets of the whole-pancreas graft. Isolated islets transplanted under the renal capsule had a markedly lower oxygen tension ( approximately 6 mmHg). The exocrine parenchyma of the native and of the transplanted pancreatic gland had an oxygen tension of approximately 30 mmHg. The lower oxygen tension in transplanted isolated islets may be one explanation for the more frequent failures of transplanted islets compared with the outcome when the whole pancreatic gland is transplanted.

Animals↗

PubMed2002

Low revascularization of experimentally transplanted human pancreatic islets.

Pancreatic islets are avascular immediately after transplantation. Although the islets are rapidly revascularized, it is uncertain whether the revascularization produces an adequate oxygenation of the transplanted islet tissue. We measured pO(2), blood flow and vascular density in mouse or human islets 1 month after transplantation to nude mice. Tissue pO(2) was measured with Clark microelectrodes. Blood perfusion was measured with laser-Doppler flow cytometry, whereas vascular density was determined in histological specimens stained for the lectin Bandeiraea simplicifolia (BS-1). Both the transplanted mouse and human islets had a pO(2) 15-20% of that in endogenous mouse islets. Moreover, the vascular density of the transplanted islets was decreased compared with that of endogenous mouse and human islets. Graft blood perfusion was approximately 50% of renal cortex blood flow. A negative correlation was found between donor age and blood perfusion of the human islet grafts. A similar correlation was seen between donor age and the total vascular density of these grafts. In conclusion, transplanted human islets had a markedly decreased vascular density and pO(2) compared with endogenous islets. This has potential implications for clinical islet transplantations, because poor vascular engraftment may significantly increase the number of islets needed to obtain insulin independence.

Adult↗

PubMedDate not supplied

Differentiating between effects of streptozotocin per se and subsequent hyperglycemia on renal function and metabolism in the streptozotocin-diabetic rat model.

BACKGROUND: The animal model with streptozotocin (STZ)-induced diabetes mellitus is associated with progressive renal disturbances. The aim of this study was to differentiate between toxic effects of STZ and the effect of hyperglycemia. Previous studies have been limited to investigating the influence of STZ on glomerular filtration rate (GFR), albuminuria and renal morphology. The present study presents a new approach when transplanting beta-cells to cure the STZ-treated animals and extends the evaluation to include both renal function and oxygen metabolism. METHODS: Animals were allocated to three groups: control animals, STZ-diabetic animals and animals rendered diabetic with an injection of STZ, followed by immediate syngeneic transplantation of approximately 1000 pancreatic islets into the splenic parenchyma. This latter procedure reversed the hyperglycemia induced by STZ. Renal function was evaluated from GFR and urinary albumin and protein leakage, while regional renal blood flow was determined using a laser-Doppler technique and oxygen tension measured with Clark-type electrodes. RESULTS: In diabetic animals, GFR increased, renal oxygen tension decreased and renal hypertrophy occurred, along with urinary leakage of protein, including albumin. Early transplantation of pancreatic islets to STZ-treated animals prevented the development of all these changes, except for proteinuria. However, an analysis of urinary protein content revealed that albuminuria was preventable by islet transplantation. CONCLUSIONS: We conclude that the urinary protein leakage in this animal model is at least partly due to direct toxic effects of STZ, whereas the other renal changes investigated in this study are due to the long-term diabetic condition.

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