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Biomedical subjects

Jose M Valdivielso

Publications and source records attributed to Jose M Valdivielso.

7 recordsLinked to original sources
PubMed2006

A forgotten method to induce experimental chronic renal failure in the rat by ligation of the renal parenchyma.

BACKGROUND: Animal models of chronic renal failure have been widely used in the experimental nephrology laboratories. The most common technique used is the 5/6 reduction of renal mass, either by surgical resection or by infarction. METHODS: In the present work, we describe a forgotten technique based in the ligation of the renal parenchyma in both renal poles. This technique combines the advantages of the resection model, like the reproducibility and homogeneity, with the ones of the infarction technique, like the absence of bleeding. RESULTS: 8 weeks after the procedure, animals showed a decrease in creatinine clearance together with an increase in plasma creatinine. Furthermore, glomeruli of animals with 5/6 nephrectomy showed a marked hypertrophy, with a glomerular volume significantly higher than control animals. Serum levels of parathyroid hormone were also increased, consistent with the development of secondary hyperparathyroidism. CONCLUSIONS: We conclude that the present technique is a valid and improved tool for the study of chronic renal failure.

Animals↗
PubMed2006

Vitamin D receptor polymorphisms and diseases.

The vitamin D endocrine system is central to the control of bone and calcium homeostasis. Thus, alterations in the vitamin D pathway lead to disturbances in mineral metabolism. Furthermore, a role for vitamin D has been suggested in other diseases, like cancer, diabetes and cardiovascular disease. Expression and nuclear activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D. Several genetic variations have been identified in the VDR. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have biological effects. To test whether there is a linkage between VDR polymorphisms and diseases, epidemiological studies are performed. In these studies, the presence of a variation of the gene is studied in a population of patients, and then compared to a control group. Thus, association studies are performed, and a link among gene polymorphisms and diseases can be established. Since the discovery of VDR polymorphisms a number of papers have been published studying its role in bone biology, renal diseases, diabetes, etc. The purpose of this review is to summarize the vast amount of information regarding vitamin D receptor polymorphisms and human diseases, and discuss its possible role as diagnostic tools.

Bone Diseases↗
PubMed2003

Increased expression of ornithine decarboxylase in distal tubules of early diabetic rat kidneys: are polyamines paracrine hypertrophic factors?

Polyamines are small biogenic molecules that are essential for cell cycle entry and progression and proliferation. They can also contribute to hypertrophy. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases in the early diabetic kidney to enable renal hypertrophy. Inhibition of ODC in early diabetes attenuates diabetic renal hypertrophy and glomerular hyperfiltration. The current studies examine the temporal profile of renal ODC protein expression and localization, intrarenal polyamine levels, and sites of proliferation in kidneys of rats during the first 7 days of streptozotocin diabetes. ODC mRNA and protein content were increased in diabetic kidneys. High-performance liquid chromatography analysis showed increased intrarenal polyamine concentrations peaking after 24 h of diabetes. A subsequent increase in the number of proliferating proximal tubular cells was detected by in vivo 5-bromodeoxyuridine (BrdU) incorporation on day 3. Surprisingly, immunohistochemical studies revealed that increased ODC protein was apparent only in distal nephrons, whereas the main site of diabetic kidney hypertrophy is the proximal tubule. These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism.

Androgens↗
PubMed2002

Vasodilatory N-methyl-D-aspartate receptors are constitutively expressed in rat kidney.

N-methyl-D-aspartate receptor (NMDA-R) is an amino acid receptor and membrane calcium channel. NMDA-R is activated by binding of coagonists, L-glutamine and L-glycine. In the brain, calcium entry via NMDA-R activates type I nitric oxide synthase (NOS I). The kidney also contains NOS I and vasodilates in response to L-glycine. In this study, NMDA-R mRNA was demonstrated in rat kidney cortex by reverse transcriptase-PCR and cDNA sequencing. NMDA-R protein was demonstrated in kidney cortex by immunoblotting. To study the functional role of renal NMDA-R, renal hemodynamic effects of NMDA-R inhibition were assessed in rats using a blocker of the NMDA calcium channel (75 mg/kg MK-801 intraperitoneally) or an inhibitor of glycine binding to NMDA-R (30 mg/kg 5,7-dichlorokynurenic acid intraperitoneally). Renal blood flow was measured by perivascular pulse Doppler. GFR was measured by 3H-inulin clearance. Measurements were made before and during glycine infusion. Both NMDA-R antagonists caused renal vasoconstriction and attenuated the renal vasodilatory response to glycine infusion. These effects were not mediated by the renal nerves. The glycine response was not inhibited by aortic snare used to mimic the effects of NMDA-R inhibitors on basal renal blood flow. NMDA-R are expressed in kidney cortex, where they exert a tonic vasodilatory influence and may account for the vasodilatory response to glycine infusion.

Analysis of Variance↗
PubMedDate not supplied

Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to the 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes (LT) from arachidonic acid. We have shown that FLAP antagonist administration decreased proteinuria in glomerulonephritic patients. In this follow-up study, we assessed the role for FLAP in a rat model of streptozotocin-induced diabetic nephropathy. METHODS: Diabetic rats were treated for 4 weeks with FLAP (BAY X-1005, 200 mg/kg) or 5-LO (Zileuton, 80 mg/Kg) antagonists. Proteinuria, renal function and LT production was assessed. We also determined protein permeability of cultured glomerular endothelial cells (which possess no 5-LO) by measuring their permeability to radiolabeled albumin with and without FLAP antagonists. RESULTS: FLAP mRNA levels increased dramatically in glomeruli from diabetic animals compared to controls. Inhibition of FLAP (but not inhibition of 5-LO) reduced proteinuria, with no effect on estimated glomerular filtration rate. Interestingly, diabetes-induced rises in urinary excretion and glomerular production of leukotrienes were not modified by the inhibitors. Increased FLAP expression in glomerular endothelial cells in culture was associated with an increase in albumin permeability, and this increase was abolished by FLAP antagonists. On the other hand, addition of LTA(4) led to increases in leukotriene formation and in permeability. This increase in permeability was also reduced by co-incubation with FLAP antagonists, whereas the increase in leukotriene synthesis was not modified. CONCLUSIONS: These results suggest a role for FLAP other than the activation of 5-LO, possibly in protein handling, and point to FLAP antagonists as anti-proteinuric agents.

Analysis of Variance↗