Gene/Protein Disease Symptom Drug Enzyme Compound
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Sevoflurane is metabolized to hexa-fluoro-isopropanol and inorganic fluoride by the human liver. Its use as an anesthetic may lead to peak plasma fluoride concentrations exceeding those seen after enflurane. Although there is no nephrotoxicity after sevoflurane anesthesia in humans with normal kidneys, those with chronically impaired renal function might be at increased risk because of increased fluoride load due to prolonged elimination half-life. In this study, measures of renal function after sevoflurane anesthesia were compared to those after enflurane in patients with chronically impaired renal function. Forty-one elective surgical patients with a stable preoperative serum creatinine concentration > or = 1.5 mg/dL were randomly allocated to receive sevoflurane (n = 21) or enflurane (n = 20) at a fresh gas inflow rate of 4 L/min for maintenance of anesthesia. Serum fluoride concentrations were measured by ion-selective electrode. Renal function (creatinine, urea, sodium, osmolality) was assessed in serum and urine preoperatively and for up to 7 days postoperatively. Peak serum inorganic fluoride concentrations were significantly higher after sevoflurane than after enflurane anesthesia (25.0 +/- 2.2 vs 13.3 +/- 1.1 microM; mean +/- SEM). Laboratory measures of renal function Laboratory measures of renal function remained stable throughout the postoperative period in both groups. No patient suffered a permanent deterioration of preexisting renal insufficiency and none required dialysis. Thus, neither sevoflurane nor enflurane deteriorated postoperative renal function in these patients with preexisting renal insufficiency. There is no evidence that fluoride released by metabolism of sevoflurane metabolism worsened renal function in these patients with stable, permanent serum creatinine concentrations more than 1.5 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane. 765 25

The development of a hydrophobic skin surface in newborn mammals such as the rat plays an important role in promoting adaptation to the abrupt change in the environment that occurs at birth. To determine whether the skin surface plays a similar role in the human neonate, we performed tests of water sorption and desorption on the chest wall of 13 term newborns. These tests were performed within the first 24 h of life on unperturbed skin (controls) and after perturbation of a contralateral site with isopropanol. The degree of surface hydration was determined by measurement of skin surface electrical capacitance, and desorption rates were calculated by 1st-order kinetic analysis. The unperturbed surface of the newborn skin exhibited a peak sorption value (change from baseline after water loading) of 435 +/- 83 pF (mean +/- SEM) and a desorption rate of 0.048 +/- 0.009 s-1. After exposure to isopropanol, the peak sorption value increased to 594 +/- 79 pF (p < 0.05) and the desorption rate decreased to 0.024 +/- 0.004 s-1 (p < 0.01). Paired sorption values were positively correlated (r2 = 0.8, p < 0.001). These results support the hypothesis that the skin surface of the human newborn, by limiting the sorption of water (or amniotic fluid) on the skin, may play a role in the adaptation to the change in environment at birth.
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PMID:Human newborn skin: the effect of isopropanol on skin surface hydrophobicity. 804 81

Pulmonary surfactant apoprotein C (SP-C) is a small, unique peptide that contributes to the reduction of alveolar surface tension. Due to the extreme hydrophobic nature of this peptide it was hitherto not possible to quantify SP-C in biological samples by immunological techniques. Using a newly developed polyclonal antibody raised against recombinant human SP-C in rabbits, we now describe an enzyme-linked immunosorbent assay (ELISA) to quantitate SP-C in bronchoalveolar lavage fluid (BALF). Solid phase binding of the hydrophobic SP-C was achieved by transfer of the standard or BALF samples (diluted in 80% isopropanol, pH 3.5) to polystyrene microtiter plates. Sequential treatment with trifluoroethanol and methanol (2x) was employed to improve antigen presentation and to minimize the influence of phospholipids. With this assay, SP-C from human, rabbit, porcine, and bovine surfactant was detectable. No cross-reactivity of the antibody to human SP-A and monomeric and dimeric SP-B was encountered. Total serum proteins did not affect ELISA signals, as evident from spiking experiments. The detection limit of the ELISA ranged below 3 ng/ml, and intra- and interassay coefficients of variation were 3.5% (n = 16) and 5.3% (n = 6), respectively. Serial dilutions of BALF showed good linearity, and excellent recovery rates were obtained upon spiking of human BALF. A mean value of 579.5 +/- 45.9 ng/ml (mean +/- SEM) SP-C was found in BALF samples of human healthy volunteers (n = 22), corresponding to 26.61 +/- 1.91 microg SP-C/mg total phospholipids (PL). SP-C levels were significantly lower in BALF of patients with acute respiratory distress syndrome (ARDS) (286.9 +/- 19.8 ng/ml [p < 0.001]; 13.92 +/- 1.93 microg SP-C/mg PL [p < 0.001], n = 48). We conclude that SP-C may be quantified with high specificity, reproducibility, and sensitivity in bronchoalveolar lavage samples by the presently described ELISA technique and that SP-C levels are significantly decreased in ARDS.
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PMID:An ELISA technique for quantification of surfactant apoprotein (SP)-C in bronchoalveolar lavage fluid. 1185 Mar 38

TiO2 thin film photocatalyst was successfully synthesized and immobilized on glass reactor tube using sol-gel method. The synthesized TiO2 coating was transparent, which enabled the penetration of ultra-violet (UV) light to the catalyst surface. Two photocatalytic reactors with different operating modes were tested: (a) tubular photocatalytic reactor with re-circulation mode and (b) batch photocatalytic reactor. A new proposed TiO2 synthesized film formulation of 1 titanium isopropoxide: 8 isopropanol: 3 acetyl acetone: 1.1 H2O: 0.05 acetic acid (in molar ratio) gave excellent photocatalytic activity for degradation of phenol and methylene blue dye present in the water. The half-life time, t1/2 of photocatalytic degradation of phenol was 56 min at the initial phenol concentration of 1000 microM in the batch reactor. In the tubular photocatalytic reactor, 5 re-circulation passes with residence time of 2.2 min (single pass) degraded 50% of 40-microM methylene blue dye. Initial phenol concentration, presence of hydrogen peroxide, presence of air bubbling and stirring speed as the process variables were studied in the batch reactor. Initial methylene blue concentration, pH value, light intensity and reaction temperature were studied as the process variables in the tubular reactor. The synthesized TiO2 thin film was characterized using SEM, XRD and EDX analysis. A comparative performance between the synthesized TiO2 thin film and commercial TiO2 particles (99% anatase) was evaluated under the same experimental conditions. The TiO2 film was equally active as the TiO2 powder catalyst.
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PMID:Performance of photocatalytic reactors using immobilized TiO2 film for the degradation of phenol and methylene blue dye present in water stream. 1548 16

Composite ceria/silica materials of 10 and 20% (w/w) were prepared by calcination, at 650 degrees C for 3 h, of the xerogels obtained by mixing the corresponding amount of a ceria precursor with freshly prepared sols of spherical silica particles (Stober particles) in their mother liquors. Two different ceria precursors were examined in this investigation. The first was a gel produced by the prehydrolysis of cerium(IV) isopropoxide in isopropanol medium, and the second was an aqueous solution of cerium(IV) ammonium nitrate. Different textural and morphological characteristics that developed by calcination were investigated by TGA, FTIR, XRD, SEM, and analyses of N2 adsorption isotherms. The results indicated that ceria dispersion and formation of mesoporous textural composite materials produced by the second precursor, cerium(IV) ammonium nitrate, are better than those produced by the first precursor, prehydrolyzed cerium(IV) isopropoxide. The results are discussed in terms of the effect of precursors and mixing media on nucleation and growth of ceria particles and their protection from sintering on calcination at the test temperature.
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PMID:Formation and characterization of different ceria/silica composite materials via dispersion of ceria gel or soluble ceria precursors in silica sols. 1592 20

The diphenylalanine peptide, the core recognition motif of the beta-amyloid polypeptide, efficiently self-assembles into discrete, well-ordered nanotubes. Here, we describe the notable thermal and chemical stability of these tubular structures both in aqueous solution and under dry conditions. Scanning and transmission electron microscopy (SEM and TEM) as well as atomic force microscopy (AFM) revealed the stability of the nanotubes in aqueous solution at temperatures above the boiling point of water upon autoclave treatment. The nanotubes preserved their secondary structure at temperatures up to 90 degrees C, as shown by circular dichroism (CD) spectra. Cold field emission gun (CFEG) high-resolution scanning electron microscope (HRSEM) and thermogravimetric analysis (TGA) of the peptide nanotubes after dry heat revealed durability at higher temperature. It was shown that the thermal stability of diphenylalanine peptide nanotubes is significantly higher than that of a nonassembling dipeptide, dialanine. In addition to thermal stability, the peptide nanotubes were chemically stable in organic solvents such as ethanol, methanol, 2-propanol, acetone, and acetonitrile, as shown by SEM analysis. Moreover, the acetone environment enabled AFM imaging of the nanotubes in solution. The significant thermal and chemical stability of the peptide nanotubes demonstrated here points toward their possible use in conventional microelectronic and microelectromechanics processes and fabrication into functional nanotechnological devices.
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PMID:Thermal and chemical stability of diphenylalanine peptide nanotubes: implications for nanotechnological applications. 1643 Feb 99

Mesoporous nanosized TiO2 and Zn(x)Ti(1-x)O(2-x) solid solution having a Zn content below 10 mol % with a particles size between 13 and 17 nm are prepared by a template-free sol-gel method followed by high-temperature supercritical drying in 2-propanol. The structural, textural, and electronic properties of the obtained nanomaterials are methodically investigated by using XRD, SEM, TEM, ED, HREM, EDX, ICP-OES, N(2) adsorption-desorption, Raman spectroscopy, and diffuse reflectance UV-vis spectroscopy. It is shown that the proposed synthesis technique leads to the formation of a Zn(x)Ti(1-x)O(2-x) solid solution based on the anatase crystal structure rather than a two-phase sample. High-resolution electron microscopy and electron diffraction indicate that the distribution of zinc atoms over the anatase structure does not lead to a considerable deformation of the crystal structure.
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PMID:Structural, textural, and electronic properties of a nanosized mesoporous ZnxTi1-xO2-) solid solution prepared by a supercritical drying route. 1685 26

The application of direct crystallization integrating with chromatography to the resolution of a racemic compound propranolol hydrochloride was studied and the crystallization progression was clearly illustrated in terms of the diagram of solubility and metastable zone widths with different enantiomeric compositions. The solubility and metastable zone widths of propranolol hydrochloride in the mixture of methanol and isopropanol were determined using an in situ Lasentec Focused Beam Reflectance Measurement (FBRM) probe. The direct crystallizations were carried out in an automatic lab reactor (Mettler Toledo LabMax) system. The optical purity of final product crystals was examined using differential scanning calorimetry (DSC), HPLC and PXRD. The crystal size distribution and morphology were analyzed using Malvern Mastersizer and Jeol SEM. It was found that optically pure crystal product could be obtained within certain safe supersaturation limit and there was no evidence of polymorph or solvate/hydrate transformation during the crystallization process. There was no selectivity of crystal growth or nucleation between the pure enantiomer and its racemate when the solution reaches the temperature lower than saturation temperature of the racemate. Hence, the critical supersaturation control of a solution was essential to obtain pure enantiomers from a partially resolved racemate.
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PMID:Application of direct crystallization for racemic compound propranolol hydrochloride. 1754 69

Enzymes are less stable in harsh conditions and hence to overcome this nature, several methodologies are being developed. It was found that crosslinked enzyme crystals are the most promising strategy for the stabilization of the enzymes [Emilia Abraham, T., Jegan Roy, J., Bindhu, L.V., Jayakumar, K.K., 2004. Crosslinked enzyme crystals of glucoamylase as a potent catalyst for biotransformations. Carbohydr. Res. 339, 1099-1104; Navia, M., St. Clair, N., 1997. Crosslinked enzyme crystals. Biosens. Bioelectron. 12, 7]. A cost effective methodology of crystallization of protease (Bacillus subtilis) with ammonium sulphate (65%, w/v) and then crosslinking the crystals with glutaraldehyde (4%, v/v) in isopropanol for 20min gave a stable and active enzyme. SEM studies showed that the protease is in small cubic shaped crystals of 1-2 microm size. Crosslinked enzyme crystal (CLEC) of protease has good stability in polar and nonpolar organic solvents, such as hexane, toluene, benzene and carbon tetrachloride and it had high thermal stability up to 60 degrees C and hence can be used as a catalyst for the biotransformation of compounds which are not soluble in aqueous medium. The CLECs were entrapped in the alginate:guar gum (3:1) composite beads which were resistant to low pH conditions in the stomach and hence was found to be useful for the oral drug delivery. This method can be used to deliver the protein and peptide drugs which require high concentrations at the delivery stage, and which normally degrades in the stomach before reaching the jejunum. Application of these pH-sensitive beads for the controlled release of subtilisin in in vitro was studied and found to be a viable strategy.
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PMID:Encapsulation of crosslinked subtilisin microcrystals in hydrogel beads for controlled release applications. 1762 42

Solid phase synthesis of polymer biotherapeutics using conventional polymers suffers from many limitations such as low synthetic yield and purity. The conventional polymers prepared by either pre- or post-functionalization strategies have no control over the point of functionalization. Hence we report a novel cross-linked polymer in which the functional groups are spatially tuned to predefined distance with optimal site isolation. This has been achieved by the design and synthesis of a tetra functional PEG, 3,3'-(PEG)bis(1-(4-vinylphenoxy)propan-2-ol) (bis(VPP)PEG). It has been incorporated at cross-linking of 1-12%, into a polystyrene network by free radical suspension polymerization. In this polymer, the distance between hydroxyl functional groups has been spatially tuned in a predefined manner by varying the length of the cross-linker backbone from ethylene glycol to PEG1000 Da and the loading capacity could be varied from 0.1 to 0.9 mmol/g. The polymer has been characterized by SEM, FTIR, and 13C NMR. The polymer exhibits excellent swelling behavior and high chemical stability. The synthetic efficiency of the polymer was demonstrated by the successful synthesis of three structural classes of PEGylated antimicrobial peptide biotherapeutics and the difficult ACP (65-74) fragment. Thus the "spatially defined" and "site isolated" synthesis within the new polymer offers a novel strategy for synthesis of difficult peptide-polymer bioconjugates. The bioassay studies shows that PEGylation of AMPs significantly reduces their hemolytic potential but the retainment of antibacterial property was dependent both on the peptide sequence and the size of PEG used.
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PMID:Peptide-polymer biotherapeutic synthesis on novel cross-linked beads with "spatially tunable" and "isolated" functional sites. 1830 62


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