Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla.
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PMID:Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat. 309 1

Anti-rat glomerular basement membrane (GBM) rabbit serum was produced by immunizing rabbits with the supernatant substance of trypsin-digested rat GBM. Nephritis was induced in rats by a single intravenous administration of 0.25 ml of anti-serum and changes in pathohistological and biochemical parameters during the process of the disease were investigated in comparison with those of Masugi nephritis and the modified type of Masugi nephritis previously reported. In light microscopic studies, histological changes seen in the kidneys closely resembled those of typical human glomerulonephritis. Changes such as hypercellularity, adhesion between capillary wall and Bowman's capsule, crescent formation and hyalinization in glomeruli and interstitial infiltration were the most pronounced on the 30th day after the anti-serum injection. In immunofluorescent studies, a linear fixation of rabbit IgG was observed along the GBM from the 1st day and the staining of a certain intensity was preserved throughout the experimental periods. A linear staining with anti-rat IgG serum was recognized from the 10th day. The fixation of fibrinogen was also seen in not only the glomerular capillary walls, but also in Bowman's space after the 10th day. Proteinuria significantly increased from the 1st day, reached a peak of 12 times the control level, and thereafter gradually decreased. The patterns of progress of urinary alkaline phosphatase and N-acetyl-beta-glucosaminidase activities were much the same as those seen in cases of proteinuria and the levels at their peak times were about 10 and 3 times control levels, respectively. Plasma urea nitrogen level transiently increased on the 5th day and then reverted to the control level by the 30th day. Plasma cholesterol levels were significantly high from the 5th to the 20th days. It is concluded that glomerular damages in this model are more severe, so-called, "nephritic type" and continue for longer periods than in cases of Masugi nephritis, however, do not differ in degree and duration from findings in the modified type of Masugi nephritis.
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PMID:[Pharmacological studies on experimental nephritic rats (11). Changes in pathohistological and biochemical parameters in anti-rat GBM rabbit serum-induced nephritis (author's transl)]. 728 45

Aminoglycosides, among the most commonly used antibiotics in neonates, have frequently been implicated in nephrotoxic reaction. Studies in adults have indicated that phospholipiduria (PLU) is rapidly increased during aminoglycoside therapy, in relation to the renal phospholipidosis these drugs are known to induce in renal cortex. We studied the effect of amikacin (AK) on PLU in male prematurely-born neonates (gestational age > 34 weeks; postnatal age < or = 2 days) by assessing the urinary excretion of 4 enzymes (N-acetyl-beta-D-glucosaminidase [NAG], alkaline phosphatase, tau-glutamyltransferase and alanine aminopeptidase) and 4 low-molecular-weight proteins (beta-2-microglobulin, clara cell protein, microalbumin and retinol-binding protein) which are currently used to monitor the development and extent of renal tubular damage. Twenty-two patients and 8 healthy (as control) neonates were enrolled in the study. Patients were treated with AK (15 mg/kg per day) given in one (qd, n = 10) or two equal injections (b.i.d., n = 12) for durations of 7-11 days. PLU and proteinuria were determined in 24-h urine sample collections, and enzymes were assessed in spot urine collected at 9 a.m. We found that in neonates, AK causes a significant increase in PLU, and in enzymuria except for NAG in the qd group. Proteinuria showed no significant change due to AK treatment. No significant differences were observed between qd and b.i.d. administrations of AK for all parameters tested. We conclude that PLU could be used in neonates as well as in adults as a non-invasive method to monitor the development of the renal phospholipidosis during aminoglycoside therapy.
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PMID:Urinary phospholipids excretion in neonates treated with amikacin. 767 71

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.
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PMID:Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity. 782 57

The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.
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PMID:Biochemical bone markers, bone mineral content, and bone mineral density in rats with experimental nephrotic syndrome. 915 58

Arterial hypertension, which represents a common problem in patients with renal transplant, contributes to the cardiovascular morbidity and mortality of these patients. The most usual immunosuppressive drugs (cyclosporine and FK-506) collaborate on the development of hypertension. Calcium channel blockers are the most habitually used antihypertensive drugs in this population, although its long-term hemodimamycs effects could be deleterious especially in transplanted patients with chronic graft nephropathy. Losartan, a specific blocker of angiotensin II (AT1) receptors, has demonstrated a potent antihypertensive effect with a good safety and tolerance profile. The glomerular effects of losartan could be useful in transplanted patients. The present open, prospective and multicenter study evaluated the efficacy and safety of losartan in the treatment of hypertension in a group of patients with a renal transplant. Seventy-six patients with systolic blood pressure > or = 140 and/or diastolic blood pressure > or = 90 mm Hg, and/or patients on therapy with one antihypertensive drug and related side effects were included. After inclusion, therapy with losartan 50 mg/24 hr was started, discontinuing the previous antihypertensive therapy and/or therapy which caused the side effects. At four weeks, if blood pressure (BP) was not controlled, hydrochlorothiazide 25 mg or furosemide 40 mg/24 hr was added. At baseline and at weeks 2, 4, 8 and 12, the following parameters were monitored: BP, creatinine, hematocrit, hemoglobin, glucose, ions, uric acid, cholesterol, triglycerides, bilirubin, SGOT, SGPT, GGT, LDH, calcium, phosphate, alkaline phosphatase, proteinuria, and both cyclosporine and FK-506 levels in whole blood. Sixty-seven patients completed the 12-week study period. Mean blood pressure decreased from 113 +/- 10 to 102 +/- 9 mm Hg at the end of the study (P < 0.0001); 38 of the 67 patients (56.7%) who completed the study had a SBP lower than 140 mm Hg and a DBP lower than 90. These blood pressures were obtained in 30 patients on monotherapy with losartan (78.9%). Proteinuria decreased significantly at week 4 and was confirmed at week 12, especially in patients with proteinuria > or = 300 mg/24 hr. Nine patients were withdrawn during the study period for different reasons. Serum creatinine showed a slight, non-clinically significant increase at week 4, remaining stable until the end of the study. Two patients developed a mild normocytic anemia, and three others presented a mild impairment of pre-existent anemia. No interactions with cyclosporine or FK-506 were described. These results indicate that losartan is effective in reducing BP in hypertensive patients with a renal transplant. It has a good tolerance profile and does not interfere with immunosuppressive therapy.
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PMID:Efficacy and safety of losartan in the treatment of hypertension in renal transplant recipients. 983 98

Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium), fractional clearance of sodium (FcNa) and potassium (FcK), urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n = 10) and 3 groups of babesiosis cases were studied: mild uncomplicated (n = 10), severe uncomplicated (n = 11), and complicated (n = 9). All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serum electrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant damage or acute renal failure.
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PMID:Renal involvement in dogs with babesiosis. 1156 13

The activities of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LD), creatine kinase (CK), amylase (AMS) and angiotensin converting enzyme (ACE) have been used to assess the toxic effects of xenobiotics that have hypoglycaemic action in hepatic, pancreatic, renal and muscle tissue. Using a validated experimental model of diabetes mellitus in rats, we ascertained whether this syndrome itself affected the serum activities of these enzymes over a 53-day period. Levels of hepatic enzymes AST, ALT and ALP were higher in the streptozotocin (STZ)-diabetic rats (group D), but were controlled by insulin therapy (group DI). AMS was reduced in group D and unchanged in group DI rats. Proteinuria was detected 1 day after STZ administration and partially controlled by insulin (group DI); its early presence in group D rats, and the lack of any change in serum ACE in this group, indicates that proteinuria is the better marker for microangiopathy. Microscopic examination of liver, kidney, heart and skeletal muscles (soleus and extensor digitorum longus) revealed various alterations in group D rat tissues, which were less pronounced in group DI. The liver, pancreas and kidney tissue-damage was consistent with the altered serum levels of AST, ALT, ALP and AMS and proteinuria. We conclude that: (i) rigorous control is required when these serum-enzyme levels are used as indicators of tissue toxicity in experimental diabetes, and (ii) LD, CK and bilirubin serum levels, which are unaffected by diabetes, can be used when testing effects of xenobiotics on tissues.
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PMID:Temporal response pattern of biochemical analytes in experimental diabetes. 1282 18

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

The aim of this study was to investigate the predictive factors which contribute to diagnosis of hantavirus infection. One hundred patients from rural areas hospitalized with a preliminary diagnosis of hantavirus infection from different hospitals in Turkey were investigated. Hantavirus infection was confirmed in 20 patients (Group 1) using immunofluorescence and immunoblot assays at the Refik Saydam National Public Health Agency. Hantaviruses were not detected in the serum of the remaining 80 patients, other infectious and non-infectious diseases being diagnosed in this group (Group 2). Patients' demographic characteristics and clinical and laboratory data on admission were examined and compared between the two groups. Fever, proteinuria, hematuria, lethargy-weakness, and nausea-vomiting were the most frequent symptoms and findings in Group 1, seen in almost all patients. Proteinuria, hematuria, muscle pain, diarrhea/abdominal pain, hypotension, shock, and sweating were observed at significantly higher levels in Group 1 compared to Group 2. Serum urea, creatinine, uric acid, lactate dehydrogenase (LDH), aspartate transaminase (AST), alkaline phosphatase (ALP), and C-reactive protein (CRP) were significantly higher, but serum platelet counts were lower in Group 1 patients. Area beneath the receiver operating characteristics (ROC) curve analysis was used to calculate the discriminative ability of various laboratory values to identify patients with hantavirus infection. This analysis revealed that, serum CRP had a 100% negative predictive value, whilst, platelet, and creatinine had 75% and 70% positive predictive values for the diagnosis of hantavirus infection. In summary, laboratory markers used in clinical practice are of great importance predicting hantavirus infections.
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PMID:Can hantavirus infections be predicted on admission to hospital? 2299 82


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