Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymeric prodrugs were prepared using methacrylic acid (MA) copolymerization with 2-hydroxyethyl methacrylate (HEMA), covalently linked with ibuprofen (HI), ketoprofen (HK), or naproxen (HN). It was previously shown that the acceptable composition of drug-linked monomer in polymeric prodrugs to prevent gastric mucosa irritation and maintain water solubility was in the range of 20-40 mol%. To investigate the applicability of these polymeric prodrugs, hydrolysis rates of HK-25, HN-29, and HI-30 (the number indicates the mole percent of the drug-linked monomers in the polymeric prodrugs), were studied in vitro with or without esterase. The polymeric prodrugs released a major fraction of the parent drugs and a fraction of the hydroxyethyl ester drug derivatives (drug-EtOH). The calculated hydrolysis rate constants and results correlated to the drug structural solubility and steric hindrance are discussed. The anti-inflammatory properties of these polymeric prodrugs were evaluated using carrageenan-induced edema test. The results indicate that HK-25 and HN-29 display greater potency to inhibit acute inflammatory processes than the free drugs over long periods. HI-30, however, retains a potency comparable to that of free ibuprofen.
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PMID:Kinetics and hydrolysis mechanism of polymeric prodrugs containing ibuprofen, ketoprofen, and naproxen as pendent agents. 1210 95

Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a k(inact) of 2.7 min(-1) and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP+, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 microM. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD+-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in alpha helices and beta sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.
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PMID:Inactivation of human glutamate dehydrogenase by aluminum. 1462 97

Magnetic resonance imaging has been used to monitor the diffusion of water at 310 K into a series of semi-IPNs of poly(ethyl methacrylate), PEM, and copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA. The diffusion was found to be well described by a Fickian kinetic model in the early stages of the water sorption process, and the diffusion coefficients were found to be slightly smaller than those for the copolymers of HEMA and THFMA, P(HEMA-co-THFMA), containing the same mole fraction of HEMA in the matrix. A second stage sorption process was identified in the later stage of water sorption by the PEM/PTHFMA semi-IPN and for the systems containing a P(HEMA-co-THFMA) component with a mole fraction HEMA of 0.6 or less. This was characterized by the presence of water near the surface of the cylinders with a longer NMR T(2) relaxation time, which would be characteristic of mobile water, such as water present in large pores or surface fissures. The presence of the drug chlorhexidine in the polymer matrixes at a concentration of 5.625 wt % was found not to modify the properties significantly, but the diffusion coefficients for the water sorption were systematically smaller when the drug was present.
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PMID:NMR imaging of the diffusion of water at 310 K into semi-IPNs of PEM and poly(HEMA-co-THFMA) with and without chlorhexidine diacetate. 1524 58

The strategy of phospholipid-based biomimicry has been used to molecularly engineer poly(2-hydroxyethyl methacrylate) [p(HEMA)]-based hydrogels for improved in vitro and potential in vivo biocompatibility. Two methacrylate-based monomers, poly(ethylene glycol) (200) monomethacrylate (PEGMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC), were incorporated at varying mole fractions of 0.0-0.5 mol% PEGMA and 0-10 mol% MPC respectively, into 3 mol% tetraethyleneglycol diacrylate (TEGDA) cross-linked p(HEMA) networks. Upon hydration of these engineered hydrogels, a reduction in receding contact angle from 22+/-1.2 degrees for p(HEMA) to 8+/-2.7 degrees for p(HEMA) containing 0.5:10 mol% PEGMA:MPC was observed, reflecting the significant increase in surface hydrophilicity with increasing PEGMA and MPC content upon prolonged hydration. Hydrogels containing MPC showed a temporal increase in hydrophilicity following continuous immersion in DI water over 5 days. Hydrogels containing 0.5 mol% PEGMA and MPC in the range of 5-10 mol% displayed reduced protein adsorption when incubated with the common extracellular matrix proteins; fibronectin, collagen or laminin, producing up to 64% less protein adsorption compared to p(HEMA). Compositional optima for cell viability and proliferation established from two-factor Central Composite design analysis of human muscle fibroblasts cultured on these hydrogels suggest that those containing PEGMA between 0.3 and 0.5 mol% and MPC levels around 5-10 mol% exhibit desirable characteristics for implant material coatings-high viability (>80%) with low proliferation (<40%), confirming a lack of cytotoxicity.
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PMID:Molecularly engineered p(HEMA)-based hydrogels for implant biochip biocompatibility. 1576 56

Herein, we report on the design and synthesis of a novel nontoxic cationic amphiphile N,N-di-n-tetradecyl-N-[2-[N',N'-bis(2-hydroxyethyl)amino]ethyl]-N-(2-hydroxyethyl)ammonium chloride (lipid 1) whose in vitro gene transfer efficacies in CHO, COS-1, MCF-7, and HepG2 cells are remarkably enhanced when used in combination with 30 mole percent added myristic acid. Reporter gene expression assay using p-CMV-SPORT-beta-gal reporter gene revealed poor gene transfer properties of the cationic liposomes of lipid 1 and cholesterol (colipid). However, the in vitro gene delivery efficacies of lipid 1 were found to be remarkably enhanced when the cationic liposomes of lipid 1 and cholesterol were prepared in the presence of 30 mole percent added myristic acid (with respect to lipid 1) as the third liposomal ingredient. The whole cell histochemical X-gal staining of representative CHO cells further confirmed the significantly enhanced gene transfer properties of the fatty acid-loaded cationic liposomes of lipid 1 and cholesterol. Electrophoretic gel patterns in the gel mobility shift assay supports the notion that better DNA release from fatty acid lipoplexes might play a role in their enhanced gene transfer properties. In addition, such myristic acid-loaded lipoplexes of lipid 1 were also found to be serum-compatible up to 30% added serum. Taken together, our present findings demonstrate that the transfection efficacies of fatty acid-loaded lipoplexes are worth evaluating particularly when traditional cationic liposomes prepared with either cholesterol or DOPE colipids fail to transfect cultured cells.
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PMID:Example of fatty acid-loaded lipoplex in enhancing in vitro gene transfer efficacies of cationic amphiphile. 1589 37

Copolymers of N-isopropylacrylamide, 2-hydroxyethyl methacryl lactate [(HEMA)-lactate] and acrylic acid (AAc) were prepared with varying mole ratios of monomers to develop copolymers with gelation properties above a certain concentration for a bioerodible, in-situ gelling material. The copolymers formed gels in situ under physiological condition. The gelation temperature of the copolymers decreased as the HEMA-lactate content of the copolymers increased due to the hydrophobicity of HEMA-lactate, and increased as the AAc content increased due to the hydrophilicity of AAc. The gels redissolve at 37 degrees C as their LCSTs increase above 37 degrees C due to the hydrolysis of the HEMA-lactate pendant groups.
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PMID:In situ-gelling, erodible N-isopropylacrylamide copolymers. 1599 39

The biocompatibility of biosmart polymer membranes synthesized from cross-linkable (2-hydroxyethyl methacrylate) (HEMA) and tetraethylene glycol diacrylate and containing different mole-percent polyethylene glycol methacrylate (PEGMA) and methacryloyloxyethyl phosphorylcholine (MPC), a phosphorylcholine-containing co-monomer, was investigated. The cytotoxicity (cell viability and proliferation) and the adhesion of extra cellular matrix proteins to these hydrogel surfaces were separately tested. Cell proliferation assays were conducted by cultivating human skeletal muscle fibroblasts onto the surfaces of these polymeric membranes prepared by in-situ polymerization in chemically derivatized 8-well cell-culture plates. The compositions containing MPC and PEGMA concentrations greater than 1.0 and 0.05 mole% respectively demonstrated good protein adhesion and cell viability (>90%) of human muscle fibroblast cells. Morphological deviances and partial colonization of the hydrogel surface has been noticed and suggests good compatibility of hydrogels for cellular viability but restricted proliferation. It is well known that the adsorption of proteins onto biomaterial surfaces modulates the cellular interaction with these surfaces. The extent of adsorption of fluorescein labeled proteins (laminin, collagen, and fibronectin) onto these polymer membrane surfaces was evaluated by measuring the resultant fluorescence intensity using a confocal fluorescence scanner.
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PMID:Molecularly engineered hydrogels for implant biocompatibility. 1727 48

We examined the in vivo mutagenicity of 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6) and benzo[a]pyrene (BaP) by using transgenic (Tg) zebrafish carrying the mutational target gene rpsL. PBTA-6 is one of the PBTA-type compounds that were recently identified in highly mutagenic river water in Japan. BaP is a well-known contaminant that is frequently found in polluted water. Both compounds are potent mutagens, as determined by using the Ames test employing S9 mix and Salmonella. Adult rpsL Tg zebrafish were exposed to 0, 7, or 10 mg/L PBTA-6 or 0, 1.5, or 3 mg/L BaP for 96 h in a water bath and the mutations in their gills and hepatopancreata were measured 2-4 weeks later. At 3 weeks after exposure, 3 mg/L BaP significantly increased the rpsL mutant frequency (MF) in the gill and hepatopancreas by 5- and 2.3-fold, respectively, as compared to control fish. Sequence analysis showed that BaP mainly induced G:C to T:A and G:C to C:G transversions, which is consistent with the known mutagenic effects of BaP. In contrast, despite its extremely high mutagenic potency in Salmonella strains, PBTA-6 did not significantly increase the MF in the zebrafish gill or hepatopancreas. Although PBTA-6 is 300 times more mutagenic than BaP in the Ames test [T. Watanabe, H. Nukaya, Y. Terao, Y. Takahashi, A. Tada, T. Takamura, H. Sawanishi, T. Ohe, T. Hirayama, T. Sugimura, K. Wakabayashi, Synthesis of 2-phenylbenzotriazole-type mutagens, PBTA-5 and PBTA-6, and their detection in river water from Japan, Mutat. Res. 498 (2001) 107-115], calculation of the mutagenicity per mole of compound indicated that PBTA-6 was 33- and <3.7-fold less mutagenic in the zebrafish gill and hepatopancreas, respectively, than BaP.
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PMID:Mutagenicity of 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6) and benzo[a]pyrene (BaP) in the gill and hepatopancreas of rpsL transgenic zebrafish. 1867 78

Phosphorus-31 and aluminum-27 nuclear magnetic resonance techniques have been used to characterize the distribution of soluble aluminophosphate species in aqueous solutions of (2-hydroxyethyl) trimethylammonium chloride (2-HETMACl), phosphoric acid, and aluminum sulfate. Soluble aluminophosphate cations obtain from reactions of hexaaqua aluminum cations [A1(H(2)O)(6)](3+), with phosphate ligands (i.e., H(3)PO(4), H(2)PO(4)(-), and acid dimers H(6)P(2)O(8) and H(5)P(2)O(7)(-)). (31)P NMR and (27)Al NMR spectroscopies are very powerful techniques for characterization of the species present in the solution. A number of solutions containing different mole ratio of Al/P were prepared. The assignment of the peaks to aluminate connectivities is attempted, clarifying earlier works and producing information on the equilibrium between various aluminum-containing species (different aluminophosphate complexes). At least seven separated resonances were observed by (31)P NMR spectroscopy indicating presence of different complexes in aluminum phosphate solutions.
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PMID:(31)P and (27)Al NMR studies of aqueous (2-hydroxyethyl) trimethylammonium solutions containing aluminum and phosphorus. 1904 Dec 78

The macromonomer of 2-hydroxyethyl methyacrylate-caprolactone (HPCL) was synthesized by the ring-opening polymerization (ROP) of epsilon-caprolactone, which was initiated by 2-hydroxyethyl methyacrylate (HEMA). Then, the graft terpolymers of NIPAAm-co-AAc-co-HEMA-g-PCL (PHNA-CL) with varying mole ratios were subsequently synthesized by free radical polymerization of HEMA-PCL, N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc). PHNA-CL was further self-assembled in different types of solvent. All the as-prepared copolymers were characterized by 1H NMR, FT-IR and GPC. Micellization behaviors of micelles were studied by TEM and DLS. The micelles exhibited a phase transition temperature which can be readily adjusted by changing pH value of the micellization system. Micelle loaded with doxorubicin (DOX) was used to evaluate the drug release behavior. The release of DOX from micelles could be controlled by changing pH value and temperature in buffer solutions. The micelles are potentially to be used as a new anticancer drug carrier for intracellular delivery.
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PMID:The pH-induced thermosensitive poly (NIPAAm-co-AAc-co-HEMA)-g-PCL micelles used as a drug carrier. 2021 89


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