Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats.

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

[Protein/creatinine ratio in single urine samples for the semiquantitation of proteinuria in children with nephrosis] / Valor da relação proteína/creatinina, em amostras únicas de urina para semi-quantificação da proteinúria, em crianças com nefrose.

OBJECTIVE: To estimate, semiquantitatively, the proteinuria of nephrotic patients by the use of the value of protein/creatinine ratio in single urine samples and determine its correlation with 24-hour proteinuria.METHODS: Analysis of 30 single urine samples and thirty 24-hour urine samples from 20 children with nephrosis followed up at the Division of Pediatric Nephrology of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. Proteinuria in single urine samples and 24-hour urine samples was measured by the turbidimetric method with 3% sulfosalicylic acid. Urinary creatinine concentration was measured by the method of Hare, modified by Haugen and Blegen, adapted to the microtechnique.RESULTS: An excellent correlation was observed between 24-hour proteinuria and the protein/creatinine ratio in single urine samples, by linear regression analysis before (r = 0.82; p < 0.001) and after logarithmic transformation (r = 0.93; p < 0.001). All patients with 24-hour proteinuria at physiological levels (less than 0.1 g/m(2)/day) had a protein/creatinine ratio of less than 0.1 (mg/mg) in single urine samples. All patients with nephrotic 24-hour proteinuria (more than 1.0 g/m(2)/day) had a protein/creatinine ratio of more than 1.0 (mg/mg). The patients with intermediate proteinuria (between 0.1 and 1.0 g/m(2)/day) had a protein/creatinine ratio distributed on the three levels.CONCLUSIONS: The protein/creatinine ratio in a single urine sample is a simple and reliable method for the evaluation of proteinuria and eliminates the errors due to inadequate 24-hour urine collection.

[Cutaneous vesicostomy in children]. / Vesicostomia cutânea em crianças.

OBJECTIVE: In this report we assessed the results obtained with cutaneous vesicostomy for the temporary diversion of urine in small children. PATIENTS AND METHODS: We analyzed the medical records of 20 patients (17 boys and 3 girls) that underwent this type of diversion at our institution. Cutaneous vesicostomy was done due to severe hydronephrosis with low renal function and/or urinary tract infection with metabolic acidosis. RESULTS: The urinary tract anomalies were posterior urethral valves in 12 children, vesicoureteral reflux in 7 and anterior urethral valve in one. Elevated levels of serum urea and creatinine were found in 16 patients during pre-operative evaluation. During the follow-up there was a reduction of hydronephrosis in all patients, and 5 progressed to chronic renal failure. These patients had worse development of weight and body lenght when compared to those with normal renal function. The post-operative complications were prolapse in 2 patients and stenosis of the stoma in 2. CONCLUSION: cutaneous vesicostomy has proved to be an useful form of urinary diversion. In our experience it is an effective and easily reversible temporary treatment for infants and children with severe hydronephrosis associated with urinary tract infection due to infravesical obstruction or vesicoureteral reflux.