Biomedical subjects

R Gazapo

Publications and source records attributed to R Gazapo.

5 recordsLinked to original sources

PubMed2001

Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure.

BACKGROUND: Parathyroid hormone (PTH)-related protein (PTHrP) is present in many normal tissues, including the kidney. Current evidence supports that PTHrP is involved in renal pathophysiology, although its role on the mechanisms of renal damage and/or repair is unclear. Our present study examined the changes in PTHrP and the PTH/PTHrP receptor (type 1) in folic acid-induced acute renal failure in rats. The possible role of PTHrP on the process of renal regeneration following folic acid administration, and potential interaction between angiotensin II (Ang II) and endothelin-1, and PTHrP, were examined in this animal model. METHODS: PTHrP, PTH/PTHrP receptor, ACE, and preproendothelin-1 (preproET-1) mRNA levels in the rat kidney were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and/or RNase protection assay. Immunohistochemistry also was performed for PTHrP, the PTH/PTHrP receptor, and Ang II in the renal tissue of folic acid-injected rats. The role of PTHrP on tubular cell proliferation following folic acid injury was investigated in vitro in rat renal epithelial cells (NRK 52E). PTHrP secretion in the medium conditioned by these cells was measured by an immunoradiometric assay specific for the 1-36 sequence. RESULTS: Using RT-PCR, PTHrP mRNA was rapidly (1 hour) and maximally increased (3-fold) in the rat kidney after folic acid, decreasing after six hours. At 72 hours, renal function was maximally decreased in these rats, associated with an increased PTHrP immunostaining in both renal tubules and glomeruli. In contrast, the PTH/PTHrP receptor mRNA (RNase protection assay) decreased shortly after folic acid administration. Moreover, PTH/PTHrP receptor immunostaining dramatically decreased in renal tubular cell membranes after folic acid. A single subcutaneous administration of PTHrP (1-36), 3 or 50 microg/kg body weight, shortly after folic acid injection increased the number of tubular cells staining for proliferating cell nuclear antigen by 30% (P < 0.05) or 50% (P < 0.01), respectively, in these rats at 24 hours, without significant changes in either renal function or calcemia. On the other hand, this peptide failed to modify the increase (2-fold over control) in ACE mRNA, associated with a prominent Ang II staining into tubular cell nuclei, in the kidney of folic acid-treated rats at this time period. The addition of 10 mmol/L folic acid to NRK 52E cells caused a twofold increase in PTHrP mRNA at six hours, without significant changes in the PTH/PTHrP receptor mRNA. The presence of two anti-PTHrP antibodies, with or without folic acid, in the cell-conditioned medium decreased (40%, P < 0.01) cell growth. CONCLUSIONS: Renal PTHrP was rapidly and transiently increased in rats with folic acid-induced acute renal failure, featuring as an early response gene. In addition, changes in ACE and Ang II expression were also found in these animals. PTHrP induces a mitogenic response in folic acid-damaged renal tubular cells both in vivo and in vitro. Our results support the notion that PTHrP up-regulation participates in the regenerative process in this model of acute renal failure and is a common event associated with the mechanisms of renal injury and repair.

Acute Kidney Injury↗

PubMed2001

Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients.

Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.

Adult↗

PubMed1998

Effects of LY-117018 HCl on bone remodeling and mineral density in the oophorectomized rat.

OBJECTIVE: LY-117018 HCl is a recently developed, selective estrogen receptor modulator and an analog of raloxifene. Its mode of action on the skeleton is similar to that of estrogens, although it does not have the same side effects. The aim of the current study was to compare the effects produced by the administration of 17alpha-ethinyl estradiol (0.1 mg/kg/day) and LY-117018 HCl (1 mg/kg/day) on bone remodeling, bone mineral density, and body and uterus weight in sham-operated and oophorectomized rats (experimental model of postmenopausal osteoporosis). STUDY DESIGN: Twelve-week-old female Wistar rats were used. Treatment was given for 3 months after oophorectomy or sham operation. Bone mineral density was determined in the lumbar spine (L2, L3, and L4) and in the left femur with use of a Hologic QDR 1000 (S/N 277) densitometer. Bone remodeling was estimated with use of the formation markers osteocalcin (bone gla protein) and alkaline phosphatase and the resorption markers type I collagen carboxyterminal telopeptide and tartrate-resistant acid phosphatase. RESULTS AND CONCLUSIONS: The newly developed derivative of raloxifene, LY-117018 HCl, offsets the reduction in bone mineral density and the accompanying increase in bone remodeling markers observed in oophorectomized rats compared with control animals. 17Alpha-ethinyl estradiol also prevents the loss of bone mass attributed to oophorectomy, but this is accompanied by an increase in body mass and a greater increase in uterus weight than that observed after treatment with LY-117018 HCl.

Acid Phosphatase↗

PubMedDate not supplied

[Peritoneal equilibrium test with hypertonic exchange: practical application in a peritoneal dialysis program].

Peritoneal equilibration test (PET) employing a 2.27%/2.5% glucose exchange is the most widely used method of to evaluating peritoneal function and small solute transport. Hypertonic (3.86%/4.25% glucose) PET has been recently recommended for the evaluation of ultrafiltration and to study certain causes of ultrafiltration failure, such as aquaporin dysfunction, through the analysis of dialysate sodium. However, there is not enough information on the optimal way to express the changes in dialysate sodium concentration, the normal range of values for this parameter, and possible adverse effects of hypertonic PET in the general population of peritoneal dialysis patients. A hypertonic PET was performed in 22 patients. Ultrafiltration failure (ultrafiltration < 0.4 L) was present in seven patients. Patients with ultrafiltration failure had higher small solute peritoneal transport and dialysate sodium concentration and had been treated with peritoneal dialysis for longer periods of time. Dialysate sodium concentration at 60 and 240 minutes was directly correlated with small solute peritoneal transport calculated as D/PCr240 (r = 0.74, p = 0.0008 y r = 0.84, p < 0.0001) and inversely correlated with ultrafiltration (r = 0.64, p = 0.0016 y r = 0.72, p = 0.0002). An absence of a dip in dialysis sodium, suggestive of aquaporin dysfunction, was only observed in one patient with a high-average small solute peritoneal transport. Dialysate sodium concentration at 60 minutes is a better discriminator between ultrafiltration failure patients than parameters such as D/PNa or the absolute dip in dialysate sodium with respect to time zero. We observed the following adverse effects: symptomatic hypotension in 2 patients with preserved ultrafiltration. In conclusion, hypertonic PET allows to confirm the diagnosis of ultrafiltration failure, but monitoring dialysate sodium concentration offers additional information only in patients with severe aquaporin dysfunction. Hypertonic PET may have adverse effects in patients without ultrafiltration failure.

Adult↗

PubMedDate not supplied

[Experience with sevelamer in peritoneal dialysis].

BACKGROUND: Sevelamer is a non-absorbable phosphorus chelator that is not a source of aluminium, calcium or base. The clinical experience with sevelamer in peritoneal dialysis and in daily clinical practice is scarce. The aim of this study is to evaluate the results of therapy of hyperphosphoremia with sevelamer on serum phosphorus and phosphorus chelators requirements, in a peritoneal dialysis clinical practice. METHODS: Sevalamer 400 mg was prescribed to peritoneal dialysis patients with hyperphosphoremia who were treated with aluminium hydroxide or with calcium salts in the absence of hypocalcemia. Fourteen patients completed 12 months of therapy. RESULTS: The initial sevelamer dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12 months. At 12 months no patient was on aluminium salts and calcium salts had been significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p = 0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p = 0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased at 12 months. No significant changes were observed in serum triglycerides, total CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned to normal at 12 months. No changes were observed in serum gamma-glutamyl-transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy. CONCLUSION: In peritoneal dialysis patients, sevelamer allows a satisfactory control of serum phosphorus levels and calcium-phosphorus product, while decreasing the amount of aluminium and calcium salts prescribed.

Epoxy Compounds↗