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)

Ifosfamide (IF) is an alkylating cytostatic derived from nitrogen mustard. In addition to its well-known urotoxic effects (hemorrhagic cystitis), several cases of Fanconi syndrome following IF therapy have been reported. No information is available concerning the pathomechanisms of this tubulotoxicity. We used the permanent renal epithelial cell line LLC-PK1 in order to investigate whether major metabolites of IF (i.e. 4-OH-IF, acrolein and chloracetyldehyde) induced the transport defects most frequently detected after IF therapy in vivo. LLC-PK1 cells of passages 162-177, grown in plastic culture dishes, were used in a confluent state. Sodium-dependent and independent fluxes of l-[3H]alanine and of D-[3H]glucose were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria and of endoplasmic reticulum were determined in cell homogenates. IF itself has no detectable effect on fluxes of l-alanine and D-glucose in LLC-PK1 cells. The IF metabolite 4-OOH-IF induces a clear inhibition of sodium-dependent fluxes of both substrates after a 24-hour exposure of cells to 100 mumol/l of 4-OOH-IF. Chloracetaldehyde induces a biphasic response of sodium-dependent fluxes of l-alanine with increased uptake rates at low concentrations (< 200 mumol/l) and with a short incubation time, while higher concentrations and long exposure of the cells leads to a reduction in sodium coupled transport. Glucose transport is affected in a comparable way, however, in contrast to alanine transport, chloracetaldehyde also stimulates sodium-independent fluxes of glucose. Acrolein is the most toxic substance tested. It severely damages cell monolayers at concentrations beyond 75 mumol/l. Sodium-coupled glucose and alanine transport is inhibited by acrolein at concentrations higher than 50 mumol/l. Sodium-coupled glucose transport is more sensitive to all metabolites tested than alanine transport. While acrolein strongly affects both transport systems, marker enzymes of the apical plasma membrane, i.e. alkaline phosphatase and leucine amino-peptidase, are not significantly inhibited, suggesting a specificity of the toxic effect for the transport proteins. We conclude that LLC-PK1 cells represent a good model for further investigation of the pathogenesis of Fanconi syndrome after IF therapy. Sodium-dependent transport systems are more sensitive to acrolein than other cell surface proteins.
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PMID:Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide. 128 22

Mitomycin C is an alkylating agent, used by intravesical instillation to treat carcinoma of the bladder. Repeated instillations can induce cystitis and an eczematous eruption affecting the palms, soles and face. If these effects are due to delayed hypersensitivity with sensitization to mitomycin C occurring in the bladder wall, it should be possible to demonstrate antigen-presenting cells in the bladder wall and positive patch tests to the drug. Using an immuno-alkaline phosphatase method we have identified CDI+ cells in bladder epithelium and submucosa and have demonstrated Birbeck granules in a few cells. In further support of our hypothesis it was also possible to demonstrate delayed type hypersensitivity in 13 out of 26 patients who had received mitomycin instillations by applying the allergen as a patch test. These results indicate that the eczematous eruption in this group of patients is most likely a hypersensitivity reaction and that it may be mediated transvesically.
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PMID:Dermatitis due to intravesical mitomycin C: a delayed-type hypersensitivity reaction? 213 92

Cefixime (CFIX) was administered 200 mg (2 divided doses) per day to 154 female patients with acute uncomplicated cystitis. Ninety four of the 154 patients who satisfied the criteria proposed by the UTI Committee, Japan were examined for the efficacy of the treatment, but 151 of 154 patients were included in the study of the side effects of the drug. The overall clinical efficacy was excellent in 80.8% and moderate in 18.1% of the patients. Ninety five (97.9%) of 97 strains which were isolated from the patients were eradicated in the urinary specimens by the treatment. Subjective side effects were observed in only one (0.7%) of the 151 patients, who complained of a sensation of heaviness in the head. No drug-related aggravation in the laboratory test was observed except for three patients who showed mild elevation glutamic pyruvic transaminase, alkaline phosphatase and blood urea nitrogen. These results showed that the oral administration of CFIX was excellent and satisfactory in the treatment for acute uncomplicated cystitis.
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PMID:[Clinical evaluation of cefixime in the treatment of acute uncomplicated cystitis]. 267 75

Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one. Granulocytopenia of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and alkaline phosphatase occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.
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PMID:Cefmenoxime: clinical evaluation. 609 26

Ifosfamide (IF) is an alkylating cytostatic drug with urotoxic (hemorrhagic cystitis) and nephrotoxic side effects. Several cases of Fanconi syndrome in children following therapy with IF were reported. Little information is available concerning the pathomechanisms of transport inhibition by IF. We used a permanent renal epithelial cell line with proximal tubular characteristics (LLC-PK1) in order to investigate the effects of IF and some of its major metabolites (4-OH-IF, chloracetaldehyde, and acrolein). LLC-PK1 cells were used in a confluent state. Sodium-dependent and sodium-independent fluxes of 32PO4 were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria, and of endoplasmic reticulum were determined in cell homogenates. IF induces a moderate stimulation of PO4 transport. 4-OH-IF also has a stimulatory effect on transport at low concentrations (up to 200 mumol/l) and with short incubation (2h), while a 24-hour exposure of cells to 100 mumol/l of 4-OH-IF has an inhibitory effect of PO4 transport. Concentrations of 4-OH-IF which inhibit transport also reduce the activity of Na(+)-K(+)-ATPase. Chloracetaldehyde, like 4-OH-IF, induces a biphasic response of PO4 transport with stimulation in the low concentration range (up to 75 mumol/l) and inhibition at higher concentrations. Chloracetaldehyde reduces the activity of succinate-cytochrome c oxidoreductase, suggesting that a defect in ATP generation might play a role in the pathogenesis of Fanconi syndrome induced by IF. Acrolein strongly damages monolayers and reduces sodium-dependent transport of PO4 to very low levels at 150 mumol/l. It reduces the activities of both Na(+)-K+ ATPase and succinate-cytochrome c oxidoreductase. Acrolein also is the only metabolite with a moderate effect on alkaline phosphatase. We conclude that sodium-dependent transport of PO4 is highly sensitive to IF metabolites. In addition to direct toxic effects of IF metabolites on transport proteins within the apical plasma membrane, damage to mitochondrial enzymes and to Na(+)-K+ ATPase which generates the electrochemical gradients for secondary active PO4 transport may play an important role in the pathogenesis of Fanconi syndrome induced by IF.
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PMID:Effect of ifosfamide metabolites on sodium-dependent phosphate transport in a model of proximal tubular cells (LLC-PK1) in culture. 750 38

OBJECTIVE To determine the effectiveness of metronomic cyclophosphamide (MC) chemotherapy (primary treatment of interest) with adjuvant meloxicam administration as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. DESIGN Retrospective case series with nested cohort study. ANIMALS 39 dogs with a histologic diagnosis of appendicular osteosarcoma that underwent limb amputation and completed carboplatin chemotherapy from January 2011 through December 2015. PROCEDURES Dogs were grouped by whether carboplatin chemotherapy had been followed with or without MC chemotherapy (15 mg/m², PO, q 24 h) and meloxicam (0.1 mg/kg [0.045 mg/lb], PO, q 24 h). The Breslow rank test was used to assess whether MC chemotherapy was associated with overall survival time (OST) and disease progression-free time (PFT) after limb amputation. RESULTS 19 dogs received carboplatin and MC chemotherapy, and 20 dogs received only carboplatin chemotherapy. No differences were identified between these groups regarding age, reproductive status, body weight, serum alkaline phosphatase activity, tumor location, or histologic grade or subtype of osteosarcoma. Median duration of MC chemotherapy for dogs in the carboplatin-MC group was 94 days (range, 7 to 586 days); this treatment was discontinued for 11 (58%) dogs when cystitis developed. Overall, 11 (28%) dogs survived to the time of analysis, for a median follow-up period of 450 days (range, 204 to 1,400 days). No difference in median PFT or OST was identified between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Maintenance MC chemotherapy following limb amputation and completed carboplatin chemotherapy was associated with no increase in PFT or OST in dogs with appendicular osteosarcoma. Cystitis was common in MC-treated dogs, and prophylactic treatment such as furosemide administration could be considered to reduce the incidence of cystitis in such dogs.
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PMID:Evaluation of metronomic cyclophosphamide chemotherapy as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. 2977 73

Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patients reaching endpoints than the ketamine cystitis group (50% and 7%, respectively, p < 0.001). After adjusting for age, sex, and initial serum creatinine level, hydronephrosis remained an independent risk factor for renal function deterioration. Ketamine-associated hydronephrosis was a poor renal outcome and strong predictor of renal function decline in chronic ketamine abusers. Elevated cholestatic liver enzyme levels correlated with the severity of ketamine-associated uropathy. Ultrasonography screening of these high-risk groups and regular renal function follow-ups are necessary.
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PMID:Risk of Renal Function Decline in Patients with Ketamine-Associated Uropathy. 3302 Apr 45

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