Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 22-year-old black male presented with erythrocytosis and proteinuria. The erythrocytosis was characterized by increased red cell mass, normal arterial oxygen saturation, and normal hemoglobin electrophoresis and oxygen affinity. There was no splenomegaly, and the white blood cell count, platelet count, serum uric acid concentration, serum B12 levels and leukocyte alkaline phosphatase activity were normal. Tumors of the liver, lung, kidney and cerebellum, which have been associated with erythrocytosis, were not found. The only associated disease was biopsy proven focal glomerulosclerosis. Renal vein thrombosis was excluded by renal venography and arteriography. This case illustrates the rarely reported association of the nephrotic syndrome and erythrocytosis. Other nephrogenic causes of erythrocytosis are mentioned, including renal cysts, tumors, renal artery stenosis and transplantation. The role of the kidney in erythropoietin production and possible mechanisms of nephrogenic erythrocytosis are discussed.
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PMID:Focal glomerulosclerosis and erythrocytosis. 50 18

Adriamycin (ADR) has a broad spectrum of antitumoral activity but is ineffective against human brain tumors. However, such tumors can be sensitive to a combination of adriamycin and lipophilic antineoplastic agents such as the nitrosoureas. CCNU, a nitrosourea, induces cholestasis in the rat and ADR is predominantly excreted via the biliary route. We decided to investigate the effect of CCNU on the nephrotic syndrome induced by ADR. Female Wistar rats were injected with a single dose of 10 mg/kg ADR and 24 h later were force fed 20 mg/kg CCNU in a single dose. Animals were sacrificed 4, 8, 15, 21, 28 or 60 days after the injection of ADR. A high rate of fatality (60%) occurred after the 21st day of treatment. Biological changes (alkaline phosphatase, SGPT, bilirubin) and ultrastructural studies showed that CCNU and CCNU + ADR induced the same degree of cholestasis. With the administered dose, CCNU is not nephrotoxic, ADR induces a nephrotic syndrome and ADR + CCNU appeared more nephrotoxic. With ADR, visceral epithelial foot process fusion was seen on day 15 and tubulo-interstitial lesions and glomerulosclerosis on day 60. With ADR + CCNU fusion of the foot process was seen on day 4, glomerular vacuolation on day 8, tubulo-interstitial alterations on day 15 and glomerulosclerosis on day 60. For both ADR and ADR + CCNU wrinkling and thickening of the basement membrane of proximal tubular cells were seen on day 60. Lipid mesangial overload was seen with ADR and was more intense with ADR + CCNU on day 60. CCNU hepatoxicity modifies the excretion of ADR and the predominantly renal excretion of ADR seems to induce earlier renal alterations in ADR + CCNU-treated rats. This study supports the concept that lipid mesangial overload may play an important role in chronic progressive glomerulosclerosis and thus the ADR + CCNU combination appears to be an interesting model in which to study these relationships.
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PMID:CCNU-adriamycin association induces earlier and more severe nephropathy in rats. 337 83

A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2-14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 micrograms per dose for patients over 30 kg and 3 micrograms for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.
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PMID:Calcitriol oral pulse therapy in children with renal osteodystrophy. 858 20

The indiscriminate and injudicious use of pesticides particularly endosulfan in agriculture and animal husbandry practices has considerably increased the risk of human health hazard. The present work was therefore undertaken to evaluate the toxic effect of endosulfan on the vital organs viz. liver and kidney of rat. Oral administration of endosulfan at the dose level of 10 mg/kg b.wt./day for two and four weeks showed toxic interference with the biochemistry and histology of rat liver and kidney. The biochemical parameters viz. Aspartate amino transferase, alanine amino transferase, acid phosphatase, alkaline phosphatase, bilirubin urea and creatinine were increased which clearly showed the hepato and nephrotoxic effect of endosulfan. Histopathologically the size of liver was increased, sinusoidal dilation, pyknotic nuclei, cytoplasmic degranulation and various nuclear aberrations were observed. Similarly pathological alterations viz. chronic glomerulonephritis, glomerulosclerosis, odenoma and glomerulus deposits were observed in the kidney.
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PMID:Hepato and nephrotoxicity in rat exposed to endosulfan. 1525 7

We encountered a 16-year-old boy with Japanese Dent's disease who exhibited renal insufficiency and an osseous disorder of the spine. Proteinuria first was noted at the age of 2 years. At 13 years, the patient underwent analysis of the CLCN5 gene, which identified missense mutation (I524K) in exon 10. During follow-up, a marked increase in urinary beta2-microglobulin was associated with mild deterioration of renal function. At the age of 15 years, hypocalcemia (7.5 mg/dl) accompanied by an increased plasma concentration of alkaline phosphatase was first detected. At that time, plasma concentration of 25(OH)D3 and 1'alpha25(OH)2D3 were low accompanied by a high plasma parathyroid hormone concentration. A renal biopsy specimen revealed tubulointerstitial alterations including mononuclear cell infiltration, partial fibrosis and focal glomerular sclerosis. Immunofluorescence revealed weak, discontinuous staining of megalin along the brushborder of renal proximal tubules. Western blotting demonstrated decreased urinary excretion of megalin. Thus, clinical manifestations and prognosis may vary in Japanese Dent's disease. Reduced megalin expression may have disturbed calcium homeostasis, leading to osseous disorder in our patient.
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PMID:A boy with Japanese Dent's disease exhibiting abnormal calcium metabolism and osseous disorder of the spine: defective megalin expression at the brushborder of renal proximal tubules. 1552 62

Hypophosphatasia is an inherited disease characterized by reduced alkaline phosphatase activity, extracellular accumulation of inorganic pyrophosphate, and impaired bone mineralization. Asfotase alfa (AA) is a recombinant human alkaline phosphatase therapy approved for treatment of pediatric-onset hypophosphatasia. Studies show promising outcome in AA-treated children with hypophosphatasia; however, data on adults with pediatric-onset hypophosphatasia are scarce. We report on a 59-year-old woman with childhood-onset hypophosphatasia and a history of multiple fractures and orthopedic procedures. Owing to renal failure (histological diagnosis: focal segmental glomerulosclerosis), hemodialysis was started in 2013. By the end of 2015, the patient was unable to walk, could only stand for 30 seconds, and was completely dependent on help for activities of daily living. After 13 months of AA therapy, the patient showed a dramatic increase in quality of life (increased mobility), reduction in pain medication, and a significant improvement in bone mineralization throughout the skeleton, including consolidation of existing fractures and no occurrence of new fractures. This case report demonstrates a relevant therapeutic success of AA treatment in an adult hemodialysis patient with childhood onset of hypophosphatasia.
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PMID:Successful Asfotase Alfa Treatment in an Adult Dialysis Patient With Childhood-Onset Hypophosphatasia. 2926 74

Medicinal plants are efficient modulators of oxidative stress associated with diabetes mellitus. This study evaluated the cardio-, reno-, and hepato-antioxidant status of hydroethanolic extract of Costus afer on streptozotocin-intoxicated diabetic rats. Experimental animals were daily administered with hydroethanolic extract of C. afer by oral intubation for eight weeks (60 days), after which the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and lipid peroxidation marker (MDA) were evaluated in the heart, liver, and kidney homogenates. Plasma biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, creatinine, and urea were determined. Meanwhile, parts of the heart, kidneys, and liver were histopathologically examined. Streptozotocin administration induced toxicity in the cardiac, hepatic, and renal tissues by stimulating significant increases (p<0.05) in the levels of CAT and SOD, GSH, and MDA. Similarly, significant increases (P<0.05) in the levels of ALT, AST, urea, and total protein were observed in streptozotocin treated rats, whereas decreases were observed in the levels of ALP, LDH, and creatinine. Following the treatments with C. afer hydroethanolic extract prevented the effect of streptozotocin by maintaining the tissue antioxidant status (CAT, SOD, GSH, and MDA) and the plasma biochemical parameters (AST, ALT, ALP, LDH, creatinine, and urea) towards the normal ranges. The histopathological examination revealed hepatovascular congestion and leucocyte infiltration as well as renovascular congestion, glomerulosclerosis, and tubular clarification in the untreated diabetic control and their absence in the group of animals treated with a high dose of C. afer extract. The findings of the present investigation suggest that C. afer possesses antioxidant activities capable of regulating drug induced tissue damage.
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PMID:Costus afer Protects Cardio-, Hepato-, and Reno-Antioxidant Status in Streptozotocin-Intoxicated Wistar Rats. 3059 93