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 single intraperitoneal injection of hexochloro-1 : 3-butadiene (HCBD) at 100 mg/kg or above produced renal tubular necrosis in the rat by 24 h. Histological examination of the kidneys indicated damage to the straight portion of the proximal tubules. Urinary analysis showed diuresis, increased proteinuria and an increase in the excretion of N-acetyl-beta-D-glucosaminidase, and alkaline phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only a mild increase in protein excretion was observed. Twenty-four hours after 200 mg/kg HCBD, i.p., there was a marked decrease in the glomerular filtration rate (inulin clearance) and in the clearance of the organic anion (p-aminohippuric acid, PAH) and the organic cation (tetraethylammonium bromide, TEA) by the kidney. HCBD did not affect the accumulation of PAH or TEA by renal cortical slices when added in vitro at a concentration up to 0.1 mM. However, a decrease in PAH, but not TEA accumulation, was seen in renal cortical slices from rats treated with HCBD 24 h previously. Mercuric chloride (HgCl2), a known nephrotoxin, was used as a positive control for these studies. HCBD appears to specifically damage the straight portion of the proximal renal tubule and thereby selectively damage the organic anion transport system.
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PMID:The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney. 53 62

Basolateral membrane vesicles were isolated from the rat kidney cortex by a modified method of cation precipitation. Different steps of preparation were analysed using the marker enzymes: Na+,K+-ATPase (for basolateral membrane), alkaline phosphatase (for apical membrane), glucose-6-phosphatase (for membranes of endoplasmic reticulum) and succinate dehydrogenase (for mitochondria). The basolateral membrane was purified by a 8-9-fold treatment with Na+,K+-ATPase, while other membrane contaminations were as low as 2% (as compared to homogenate). The transport of 3H-p-aminohippurate (3H-PAH) by basolateral membrane vesicles was measured under different experimental conditions. The 3H-PAH uptake was found to be Na-gradient dependent. The initial rate of 3H-PAH uptake in the presence of NaCl gradient (500 pM/mg X min) was higher than without the gradient (88 pM/mg X min). It is concluded that the PAH transfer across the basolateral membrane may be energized by the Na+ chemical gradient.
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PMID:[Effect of a NaCl gradient on the transport of para-aminohippuric acid into the vesicles of the basolateral membrane of the kidney cortex]. 359 Mar 16

Repeated exposure to coal liquefaction products produces a broad range of systemic effects. Among these, growth suppression, anaemia, leucocytosis and other haematological disorders are most prominent. Bone marrow, liver and kidney are the target organs affected by treatment. The effects are more severe with heavy distillates and male rats are more sensitive than females. Other changes included increased serum transaminases, alkaline phosphatase and cholesterol. Depending on the route of administration, the skin or lung may also be affected. Inhalation exposure produces the most severe changes, and oral exposure the least. Distillates containing N-PAHs and sulphur-containing PAHs are also more biologically active. Teratological effects were only observed if animals were exposed to the heavy distillate. Similarly, heavy distillates have mutagenic or carcinogenic properties. Teratological effects, as well as mutagenicity and carcinogenicity, of the coal liquefaction distillates seem to be linked to their PAH content, especially the N-PAHs. From the data presented in this review, it should become evident that the potential effects of coal liquefaction products on human health could be severe, especially with long-term exposure. Limited information exists on the occupational effects to coal liquefaction materials because most of the work to date has been with pilot plants. Careful and good judgement is required in order to extrapolate data from pilot plants to commercial-scale production. Experience in health effects of workers in the petroleum industry and coke-oven operations can serve as a guide for the implementation of industrial hygiene programmes for coal liquefaction operations. These programmes include engineering controls, health education, personal monitoring and hygienic practices, medical surveillance and long-term epidemiology studies, and they should be implemented to make coal liquefaction a healthy and environmentally sustainable industry.
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PMID:Toxicology of coal liquefaction products: an overview. 796 36

The consumption of plants containing atractyloside, a diterpenoid glycoside, causes selective proximal tubule injury leading to renal failure and death in humans. The underlying mechanisms responsible for its toxicity are still not well understood. The present study was therefore carried out to determine the mechanism and the exact sequence of events that lead to molecular toxic injury. A comparative study using renal cortical slices, suspension of freshly isolated renal proximal tubular fragments and glomeruli of male Wistar rat was made. These in vitro systems were exposed to 100-1000 mM atractyloside for 2-3 h at 37 degrees C. Atractyloside caused a significant alteration in various toxicity parameters in a concentration- and time-dependent manner in renal cortical slices and proximal tubular fragments, but not in glomeruli. The earliest change following exposure to atractyloside (1000 microM) was a significant reduction of intracellular adenosine 5'-triphosphate (ATP) content occurring within 1 h in the tubules and 2 h in slices. The significant depletion of reduced glutathione (GSH) inhibitor of p-aminohippuric (acid) (PAH) uptake and gluconeogenesis occurred simultaneously following loss of cellular energy. These events were only limited to the renal cortical slices and proximal tubular fragments. Increased severity of cellular injury resulted in cytotoxicity with the significant increase in the leakage of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in proximal tubular fragments (occurring at 2 h) and renal cortical slices (occurring at 3 h). There were, however, no alterations in oxidized glutathione (GSSG) levels or in the ratio of GSH/GSSG. Only limited lipid peroxidation in proximal tubular fragments and glomeruli was observed at atractyloside concentrations of 500 microM and above. In all cases of toxicity, the glomeruli were unaffected. Pretreatment of slices or fragments with probenecid (1.0 mM) failed to completely abolish atractyloside toxicity. These data demonstrate dose- and time-dependent toxicity of atractyloside and clearly confirmed the proximal tubular fragments as the target tissue. Atractyloside exhibits a toxicity profile that indicates early alteration in mitochondrial function and consequently loss of cellular energy, followed by reduced metabolic function and transport processes and ultimately cell death. This appears to be the most likely mechanism by which atractyloside exerted its acute cytotoxicity. Renal cortical slices, which maintain proximal tubule and glomeruli in their anatomic relationship, responded similarly to atractyloside toxicity as the proximal tubular fragments, and might be suggested as the most suitable in vitro model system for studying the mechanisms of atractyloside toxicity as they are more likely to mirror changes seen in the whole organ.
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PMID:Atractyloside nephrotoxicity: in vitro studies with suspensions of rat renal fragments and precision-cut cortical slices. 1090 Apr 5

The development of chemical reactions in nanospaces is of paramount importance for the development of active nanodevices, particularly in nanofluidics. It has been shown in a previous paper that phospholipid vesicles can be incorporated without spontaneous bilayer rupture into poly-L-glutamic acid/poly(allylamine) (PGA/PAH) multilayered polyelectrolyte films. The aim of the present study was to use such a system as an "embedded submicronic reactor" able to trigger precipitation of calcium phosphates within closed spaces through an enzymatic reaction, the enzyme also being encapsulated in the vesicle interior. To this aim, large unilamellar vesicles (LUVs) were produced containing calcium ions as active ions in the mineralization process, spermine as an activator of crystal growth, and alkaline phosphatase as a catalyst to convert phosphate esters into phosphates. After stabilization by adding a layer of poly-(D-lysine), these vesicles were embedded in a (PGA-PAH)n film. A paranitrophenyl phosphate containing solution was then put in contact with this film. It is shown by means of infrared spectroscopy in the attenuated total reflection mode that, consecutively to this contact, calcium phosphates are growing inside the embedded vesicles. By using scanning near-field fluorescence microscopy, it is demonstrated that the alkaline phosphatase enzymes are most probably located inside the vesicles after their embedding. In addition, atomic force microscopy was used to show, after chemical removal of the organic top layer of the film, that the inorganic platelets produced after the precipitation reaction are localized in volumes of similar size and shape as that of the vesicles into which the phosphate ester hydrolysis and subsequent precipitation reaction did occur.
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PMID:Layer-by-layer self-assembled polyelectrolyte multilayers with embedded liposomes: immobilized submicronic reactors for mineralization. 1648 29

Treatment of true Precocious Puberty (PP) with GnRH agonist can improve final adult height by suppressing gonadotropin and sex hormone levels that delays the fusion of long bone epiphyseal growth plates. However, deprivation of estrogen may affect the acquisition of peak bone mass, especially in individuals with low calcium intake. Ten Thai girls with idiopathic true PP were evaluated for Bone Mineral Density (BMD) and body composition by DXA scanner (Hologic, Inc) before and after GnRH agonist therapy for 1 year. During treatment, all children were allowed to consume a normal diet without extra calcium supplementation. In addition, serum calcium, phosphate, alkaline phosphatase and osteocalcin were also measured. The results showed that GnRH agonist could improve predicted adult height from 149.4 +/- 5.4 to 153.6 +/- 6.8 cm (p < 0.001). Serum osteocalcin, representing the bone marker formation, decreased from 184.2 +/- 66.7 to 108.6 +/- 35.3 ng/mL (p = 0.012) However, the treatment had no negative effects on BMD lumbar spine and total BMD but increased percentage of fat mass from 25.7 +/- 5.2 to 31.6 +/- 5.5%. (p =0.007). In conclusion, treatment with GnRH agonist in Thai girls with true PP for 1 year can improve PAH without negative effects on BMD but a longer period of treatment needs to be studied.
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PMID:Bone mineral density and body composition in Thai Precocious Puberty girls treated with GnRH agonist. 1704 29

Multilayer assemblies of polyelectrolytes, for protein immobilization, have been created within the membrane pore domain. This approach was taken for two reasons: (1) the high internal membrane area can potentially increase the amount of immobilized protein, and (2) the use of convective flow allows uniform assembly of layers and eliminates diffusional limitations after immobilization. To build a stable assembly, the first polyelectrolyte layer was covalently attached to the membrane surface and inside the pore walls. Either poly(L-glutamic acid) (PLGA) or poly(L-lysine) (PLL) was used in this step. Subsequent deposition occurs by multiple electrostatic interactions between the adsorbing polyelectrolyte [poly(allylamine) hydrochloride (PAH) or poly(styrenesulfonate) (PSS)] and the oppositely charged layer. Three-layer membranes were created: PLL-PSS-PAH or PLGA-PAH-PSS, for an overall positive or negative charge, respectively. The overall charge on both the protein and membrane plays a substantial role in immobilization. When the protein and the membrane are oppositely charged, the amount immobilized and the stability within the polyelectrolyte assembly are significantly higher than for the case when both have similar charges. After protein incorporation in the multilayer assembly, the active site accessibility was comparable to that obtained in the homogeneous phase. This was tested by affinity interaction (avidin-biotin) and by carrying out two reactions (catalyzed by glucose oxidase and alkaline phosphatase). Besides simplicity and versatility, the ease of enzyme regeneration constitutes an additional benefit of this approach.
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PMID:Layer-by-layer-assembled microfiltration membranes for biomolecule immobilization and enzymatic catalysis. 1710 8

Given the effects of environmental pollution and different biotic factors on some important biochemical markers, as enzymes, two fish species inhabiting the Sariyar Dam Lake, Turkey have been investigated. Ethoxyresorufin O-deethylase, glutathion S-transferase, lactate dehydrogenase, alkaline phosphatase, acid phosphatase, and alanine and aspartate amino transferase activities have been measured in liver samples of Cyprinus carpio and Capoeta tinca. Also, brain acetylcholinesterase and carboxylesterase activities have been measured for the same samples. Selected enzymes confirmed that Sariyar basin is polluted by urban wastes and agricultural and industrial activities for many years. Organochlorine (OC) pesticide residues, caused by intensive agricultural activities, have also been observed in water, sediment samples, and adipose tissues of carp. Monitored results showed that SDL was polluted by different kinds of OC compounds such as DDT and its derivatives which are accumulated in adipose tissues of carp. Highest accumulation was found for beta-BHC in carp. The changes of enzyme activities in this study may be related to environmental pollution, while enzyme activity variations could be attributed to variable pollutants and variable concentrations of these pollutants. The results highlighted the potential convenience of these biomarkers to be used as components of environmental monitoring program in risk assessment studies in SDL. Since a seasonal variation in selected enzyme activities was found, the possible implications of such variability in the use of these enzymes as environmental biomarkers are also discussed. Hepatic cytosolic EROD did not show any significance according to the pollution factors in the lake which may be attributed to relatively less contamination by organic compounds such as PAH products.
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PMID:Ecotoxicological assessment of water pollution in Sariyar Dam Lake, Turkey. 1758 95

Layer-by-layer deposition of polyelectrolyte multilayer (PEM) membranes has recently been applied successfully to a number of biomedical applications. This simple and versatile technique provides a broad surface modification platform, for example, for the display of biomolecules such as cell-adhesion peptides. In this work, we investigated the effects of PEM coatings on RGD-immobilization and osteoblast cell culture. RGD-containing peptides were conjugated to the amino groups of poly(allylamine hydrochloride) (PAH), and then adsorbed on top of 10-layer PAH/poly(acrylic acid) (PAA) multilayer membranes that were assembled at either pH 2.0 or pH 6.5. MG63 osteoblast-like cells were then seeded and cultured on the RGD-conjugated surfaces. We found that the cells adhered to and grew better on the RGD-conjugated PEM membranes. Furthermore, the cells grew better on the RGD-conjugated PEM coatings assembled at pH 6.5 than those assembled at pH 2.0. On the other hand, MG63 cells exhibited better differentiated phenotype on the pH 2.0 coatings compared to the pH 6.5 coatings with respect to alkaline phosphatase activity and calcium deposition, while cells did not express osteoblast phenotype on the PAH surfaces. These results clearly show that the base PEM membranes play an important role in RGD-immobilization and osteoblast functions.
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PMID:Modulation of RGD-functionalized polyelectrolyte multilayer membranes for promoting osteoblast function. 2017 92

Deposition of layer-by-layer polyelectrolyte multilayer (PEM) films has been a widely applied surface modification technique to improve the biocompatibility of biomaterials. The objective of this study was to investigate the impact of the deposition of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) multilayer films on adhesion, growth and differentiation of osteoblasts-like MG63 cells. PAH and PAA were deposited sequentially onto tissue culture polystyrene at either pH 2.0 or pH 6.5 with 4-21 layers. While the MG63 cells attached poorly on the PAH/PAA multilayer films deposited at pH 2.0, while the cells adhered to the PEM films deposited at pH 6.5, depending on layer numbers. Cell adhesion, proliferation and osteogenic activities (alkaline phosphatase activity, expression of osteogenic marker genes and mineralization) were highest on the 4-layer PAH/PAA film and decreased with increasing layer numbers. On the other hand, the behavior of MG63 cells did not show any difference on the adjacent even and odd layers, except PEM4 and PEM5, i.e. the surface charges of the PAH/PAA multilayer films with over ten layers seem indifferent to osteoblastic functions. The results in this study suggested that the mechanical properties of PEM films may play a critical role in modulating the behavior of osteoblasts, providing guidance for application of PEM films to osteopaedic implants.
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PMID:Modulation of the functions of osteoblast-like cells on poly(allylamine hydrochloride) and poly(acrylic acid) multilayer films. 2179 25


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