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- Comparative Effectiveness of Different Oral Antibiotics Regimens for Treatment of Urinary Tract Infection in Outpatients: An Analysis of National Representative Claims Database. [JOURNAL ARTICLE]
- Medicine (Baltimore) 2014 Dec; 93(28):e304.
There are very limited data on the postmarketing outcome comparison of different guideline antibiotic regimens for patients with urinary tract infections (UTIs).We carried out a population-based comparative effectiveness study from year 2000 through 2009, using the administrative data of 2 million patients from the National Health Informatics Project of Taiwan. Treatment failure was defined as either hospitalization or emergency department visits for UTI. Odd ratios were computed using conditional logistic regression models matched on propensity score.We identified 73,675 individuals with UTI, of whom 54,796 (74.4%) received trimethoprim-sulfamethoxazole (TMP-SMX), 4184 (5.7%) received ciprofloxacin, 3142 (4.3%) received levofloxacin, 5984 (8.1%) received ofloxacin, and 5569 (7.6%) received norfloxacin. Compared with TMP-SMX, the composite treatment failure was significantly lowered for norfloxacin in propensity score (PS) matching analyses (OR, 0.73; 95% CI, 0.54-0.99). Both norfloxacin (PS-matched OR, 0.68; 95% CI, 0.47-0.98) and ofloxacin (PS-matched OR, 0.70; 95% CI, 0.49-0.99) had significantly lowered composite treatment failure rate when compared with ciprofloxacin. Subgroup analysis suggested that both norfloxacin and ofloxacin were more effective in female patients without complications (W/O indwelling catheters, W/O bedridden status and W/O spinal cord injury), when compared with either TMP-SMX or ciprofloxacin.Among outpatients receiving oral fluoroquinolone therapy for UTIs, there was evidence of superiority of norfloxacin or ofloxacin over ciprofloxacin or TMP-SMX in terms of treatment failure. Given the observational nature of this study and regional difference in antibiotic resistance patterns, more studies are required to validate our results.
- Intramolecular Frustrated Lewis Pair with the Smallest Boryl Site: Reversible H2 Addition and Kinetic Analysis. [JOURNAL ARTICLE]
- Angew Chem Int Ed Engl 2014 Dec 17.
Ansa-aminoborane 1 (ortho-TMPC6 H4 BH2 ; TMP=2,2,6,6-tetramethylpiperid-1-yl), a frustrated Lewis pair with the smallest possible Lewis acidic boryl site (BH2 ), is prepared. Although it is present in quenched forms in solution, and BH2 represents an acidic site with reduced hydride affinity, 1 reacts with H2 under mild conditions producing ansa-ammonium trihydroborate 2. The thermodynamic and kinetic features as well as the mechanism of this reaction are studied by variable-temperature NMR spectroscopy, spin-saturation transfer experiments, and DFT calculations, which provide comprehensive insight into the nature of 1.
- Metaproteomic Analysis of Bio-Cake Proteins to Understand Membrane Fouling in a Submerged Membrane Bioreactor. [JOURNAL ARTICLE]
- Environ Sci Technol 2014 Dec 17.
Metaproteomic analyses, including two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separation and matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)-TOF mass spectrometer (MS) detection, were used to trace and identify bio-cake proteins on membranes in a bench-scale submerged membrane bioreactor (MBR). 2D-PAGE images showed that proteins in the bio-cake at a low transmembrane pressure (TMP) level (i.e., before the TMP jump, S3) had larger gray intensities in the pH 5.5-7.0 region regardless of the membrane flux, similar to soluble microbial product (SMP) proteins. However, the bio-cake at a high TMP level (i.e., after the TMP jump, S2 and S4) had many more proteins in the pH range of 4.0-5.5, similar to extracellular polymeric substance (EPS) proteins. Such similarities between bio-cake proteins and SMP or EPS proteins can be useful for tracing the sources of proteins resulting in membrane fouling. In total, 183 differentially abundant protein spots were marked in the three bio-cakes (S2, S3 and S4). However, only 32 protein spots co-occurred in the 2D gels of the three bio-cakes, indicating that membrane fluxes and TMP evolution levels had significant effects on the abundance of proteins. Based on the MS and MS/MS data, 23 of 71 protein spots were successfully identified. Of the 23 proteins, outer membrane proteins (Omp) were a major contributor (60.87 %). These Omps were mainly from potential surface colonizers such as Aeromonas, Enterobacter, Pseudomonas and Thauera. Generally, the metaproteomic analysis is a useful alternative to trace the sources and compositions of bio-cake proteins on the levels of molecules and bacteria species because it can provide new insight into membrane fouling.
- Impact of anti-peroxynitrite-damaged-thymidine- monophosphate antibodies on disease activity in patients with systemic lupus erythematosus. [Journal Article]
- Nucleosides Nucleotides Nucleic Acids 2015 Jan 2; 34(1):56-68.
Present study probes the role of peroxynitrite (ONOO(-))-modified thymidine-5'-monophosphate (TMP) in SLE patients with different disease activity scores according to the SLE Disease Activity Index (SLEDAI). Serum analysis showed significant increased number of subjects positive for anti-ONOO(-)-TMP-protein antibodies in SLE patients with different SLEDAI scores. Interestingly, the levels of these antibodies were significantly higher among SLE patients, whose SLEDAI scores were ≥20. In addition, a significant correlation was observed between the levels of anti-ONOO(-)-TMP-protein antibodies and the SLEDAI score (r = 0.595, p < 0.0001). In short, this study shows a positive association between anti-ONOO(-)-TMP-protein antibodies and SLEDAI. The stronger response observed in patients with higher SLEDAI scores suggests that anti-ONOO(-)-TMP-protein antibodies may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.
- An antifungal coating for dental silicones composed of chlorhexidine nanoparticles. [JOURNAL ARTICLE]
- J Dent 2014 Dec 12.
The aims of this study were to synthesise a range of chlorhexidine-containing nanoparticles (CHX-NPs), and investigate the feasibility of using these as an antifungal coating for dental silicones.CHX-NPs were precipitated in aqueous reaction by mixing solutions of CHX digluconate with solutions of sodium triphosphate (TP), trimetaphosphate (TMP) or hexametaphosphate (HMP). CHX-NPs were deposited on commercial dental silicones by immersion coating, and these were characterised for hydrophilicity (contactangle) and water uptake (mass change). Soluble CHX elution into artificial saliva was measured using ultraviolet spectrophotometry. Antifungal efficacy against Candida albicans was investigated using a cell proliferation assay.Coating silicones with CHX-NPs did not significantly affect hydrophilicity, as assessed using water contact angle, or water uptake as assessed by mass change following 16 weeks' immersion in artificial saliva. CHX-NP-coated silicone specimens released soluble CHX into artificial saliva. The salt of CHX and the immersion time affected the rate, concentration and duration of CHX release, with CHX-HMP exhibiting a slow, sustained release and CHX-TP and CHX-TMP exhibiting a faster, more concentrated release. C. albicans metabolic activity was inhibited by presence of CHX-HMP-NPs in suspension.CHX-NPs provided a localised, controlled dose of soluble CHX at the surface of dental silicones without adversely affecting hydrophilicity or water uptake. CHX-HMP NPs provided effective antifungal control of C. albicans in a cell proliferation assay. Coating materials with these nanoparticles could be an effective way of delivering low, but clinically relevant, concentrations of chlorhexidine in the oral environment. Clinical Significance: Denture stomatitis is a common oral infection and is associated with fungal infestation of denture soft lining and obturator materials, which are often silicones such as those used here. Our study suggests that CHX-NPs may be a useful strategy in design of antifungal coatings for these materials.
- Heart Mitochondrial TTP Synthesis and the Compartmentalization of TMP. [JOURNAL ARTICLE]
- J Biol Chem 2014 Dec 11.
The primary pathway of TTP synthesis in the heart requires thymidine salvage by the mitochondrial thymidine kinase 2 (TK2). However, the compartmentalization of this pathway and the transport of thymidine nucleotides are not well understood. We investigated the metabolism of [3H]-thymidine or [3H]-TMP as precursors of [3H]-TTP in isolated intact or broken mitochondria from rat heart. The results demonstrated that [3H]-thymidine was readily metabolized by the mitochondrial salvage enzymes to TTP. The equivalent addition of [3H]-TMP produced far less [3H]-TTP than the amount observed with [3H]-thymidine as the precursor. Using AZT to inhibit TK2 the synthesis of [3H]-TTP from [3H]-TMP was effectively blocked, demonstrating that synthesis of [3H]-TTP from [3H]-TMP arose solely from the de-phosphorylation of [3H]-TMP to [3H]-thymidine. To determine the role of the membrane in TMP metabolism, mitochondrial membranes were disrupted by freezing and thawing. In broken mitochondria, [3H]-thymidine was readily converted to [3H]-TMP but further phosphorylation was prevented even though the energy charge was well maintained by addition of oligomycin A, phosphocreatine and creatine phosphokinase. The failure to synthesize TTP in broken mitochondria was not related to a loss of membrane potential or inhibition of the electron transport chain as confirmed by addition of FCCP and KCN, respectively in intact mitochondria. In summary, these data taken together suggest that the thymidine salvage pathway is compartmentalized such that TMP kinase prefers TMP synthesized by TK2 over medium TMP, and this is disrupted in broken mitochondria.
- Synthesis and structure-activity relationships of pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization. [JOURNAL ARTICLE]
- Eur J Med Chem 2014 Dec 2.:603-619.
Three series of compounds; pyridinyl-1H-1,2,3-triazoles, pyridinyl-1H-1,2,3-triazolylisoxazoles and pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles with TMP moiety were designed, synthesized and screened for their anti-cancer and anti-tubulin properties. By sequentially designing three series of compounds comprising of dihydroisoxazole in the linker, a small substituent like chlorine on one side (R(1)) and aromatic group (R) on the pyridine ring, we have optimized the anti-cancer as well as anti-tubulin activity. Pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles 28b and 28c were found to be potent anti-cancer agents against all the cell lines tested with a concomitant accumulation of cells in the G2/M phase of the cell cycle. Molecular modeling suggests that the trimethoxyphenyl ring in 28b and 28c occupies the cholchicine binding domain of β-tubulin, whereas, the dihydroisoxazole extends towards the interface of α,β-tubulin.
- Effects of enrofloxacin, ciprofloxacin, and trimethoprim on two generations of Daphnia magna. [JOURNAL ARTICLE]
- Ecotoxicol Environ Saf 2014 Dec 9.:152-158.
Multigenerational tests on Daphnia magna were performed exposing two subsequent generation to enrofloxacin (EFX) and its metabolite ciprofloxacin (CPX), and to trimethoprim (TMP). Mortality rate of 100% and 50% was detected in F0 at concentrations of ≥13mgL(-1) (EFX) and 50mgL(-1) (TMP), respectively. In F1 with respect to F0, both for growth and reproduction, a worsening trend of the response with EFX, a similar response with CPX and an attenuating trend with TMP was observed. Furthermore, the lowest EC20 for reproduction inhibition (1.3mgL(-1)) was calculated for F1 exposed to EFX. However, other experimentations, longer and more complex, are necessary in order to confirm that EFX is more hazardous to daphnids than CPX and TMP. EC50 measured for the three assayed antibacterials were in the 6.5-37mgL(-1) range therefore environmental unrealistic, except in case of exceptional contaminations that may occur in relation to poorly controlled wastewaters from pharmaceutical factories or excessive use of prophylactic treatments in aquaculture.
- Anodic Substitution Reaction of Proline Derivatives Using the 2,4,6-Trimethoxyphenyl Leaving Group. [JOURNAL ARTICLE]
- Org Lett 2014 Dec 11.
An efficient method for modifying a proline moiety through anodic carbon-carbon bond cleavage is developed. Use of the 2,4,6-trimethoxyphenyl (TMP) moiety as a leaving group at the 5-position allows the incorporation of various functional groups for modification in both the N- and C-terminal direction due to the stability of the N1-C5-C linkage. This approach also enables anodic substitution reactions using reactants with lower oxidation potential compared to N-carbonyl bonds.
- Copper-Catalyzed Formal CH Carboxylation of Aromatic Compounds with Carbon Dioxide through Arylaluminum Intermediates. [JOURNAL ARTICLE]
- Chem Asian J 2014 Dec 9.
The CH bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3 Al(TMP)Li followed by the NHC-copper-catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X-ray crystallographic analyses, thus offering important information on the reaction mechanism.