Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Drug-induced aseptic meningitis secondary to trimethoprim/sulfamethoxazole: a headache to be aware of. [Journal Article]
- CJEM 2014 Sep 1; 16(5):421-4.
ABSTRACTTrimethoprim/sulfamethoxazole (TMP/SMX), also known as Septra, is a commonly encountered and prescribed antibiotic in emergency department patients. The side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects, including Stevens-Johnson syndrome and drug-induced aseptic meningitis, have been reported. We discuss the case of a 33-year-old woman who presented to our emergency department with the signs and symptoms of meningeal inflammation after being prescribed TMP/SMX 3 days earlier for an abscess with cellulitis.
- Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. [Journal Article]
- Indian J Med Res 2014 Jul; 140(1):130-7.
Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics.Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method.All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX.o0 ur study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents.
- Factors Affecting Hydrogen-Tunneling Contribution in Hydroxylation Reactions Promoted by Oxoiron(IV) Porphyrin π-Cation Radical Complexes. [JOURNAL ARTICLE]
- Inorg Chem 2014 Sep 15.
Hydrogen atom transfer with a tunneling effect (H-tunneling) has been proposed to be involved in aliphatic hydroxylation reactions catalyzed by cytochrome P450 and synthetic heme complexes as a result of the observation of large hydrogen/deuterium kinetic isotope effects (KIEs). In the present work, we investigate the factors controlling the H-tunneling contribution to the H-transfer process in hydroxylation reaction by examining the kinetics of hydroxylation reactions at the benzylic positions of xanthene and 1,2,3,4-tetrahydronaphthalene by oxoiron(IV) 5,10,15,20-tetramesitylporphyrin π-cation radical complexes ((TMP(+•))Fe(IV)O(L)) under single-turnover conditions. The Arrhenius plots for these hydroxylation reactions of H-isotopomers have upwardly concave profiles. The Arrhenius plots of D-isotopomers, clear isosbestic points, and product analysis rule out the participation of thermally dependent other reaction processes in the concave profiles. These results provide evidence for the involvement of H-tunneling in the rate-limiting H-transfer process. These profiles are simulated using an equation derived from Bell's tunneling model. The temperature dependence of the KIE values (kH/kD) determined for these reactions indicates that the KIE value increases as the reaction temperature becomes lower, the bond dissociation energy (BDE) of the C-H bond of a substrate becomes higher, and the reactivity of (TMP(+•))Fe(IV)O(L) decreases. In addition, we found correlation of the slope of the ln(kH/kD) - 1/T plot and the bond strengths of the Fe═O bond of (TMP(+•))Fe(IV)O(L) estimated from resonance Raman spectroscopy. These observations indicate that these factors modulate the extent of the H-tunneling contribution by modulating the ratio of the height and thickness of the reaction barrier.
- Combined Experimental and Theoretical Study on the Reactivity of Compounds I and II in Horseradish Peroxidase Biomimetics. [JOURNAL ARTICLE]
- Chemistry 2014 Sep 12.
For the exploration of the intrinsic reactivity of two key active species in the catalytic cycle of horseradish peroxidase (HRP), Compound I (HRP-I) and Compound II (HRP-II), we generated in situ [Fe(IV) O(TMP(+.) )(2-MeIm)](+) and [Fe(IV) O(TMP)(2-MeIm)](0) (TMP=5,10,15,20-tetramesitylporphyrin; 2-MeIm=2-methylimidazole) as biomimetics for HRP-I and HRP-II, respectively. Their catalytic activities in epoxidation, hydrogen abstraction, and heteroatom oxidation reactions were studied in acetonitrile at -15 °C by utilizing rapid-scan UV/Vis spectroscopy. Comparison of the second-order rate constants measured for the direct reactions of the HRP-I and HRP-II mimics with the selected substrates clearly confirmed the outstanding oxidizing capability of the HRP-I mimic, which is significantly higher than that of HRP-II. The experimental study was supported by computational modeling (DFT calculations) of the oxidation mechanism of the selected substrates with the involvement of quartet and doublet HRP-I mimics ((2,4) Cpd I) and the closed-shell triplet spin HRP-II model ((3) Cpd II) as oxidizing species. The significantly lower activation barriers calculated for the oxidation systems involving (2,4) Cpd I than those found for (3) Cpd II are in line with the much higher oxidizing efficiency of the HRP-I mimic proven in the experimental part of the study. In addition, the DFT calculations show that all three reaction types catalyzed by HRP-I occur on the doublet spin surface in an effectively concerted manner, whereas these reactions may proceed in a stepwise mechanism with the HRP-II mimic as oxidant. However, the high desaturation or oxygen rebound barriers during CH bond activation processes by the HRP-II mimic predict a sufficient lifetime for the substrate radical formed through hydrogen abstraction. Thus, the theoretical calculations suggest that the dissociation of the substrate radical may be a more favorable pathway than desaturation or oxygen rebound processes. Importantly, depending on the electronic nature of the oxidizing species, that is, (2,4) Cpd I or (3) Cpd II, an interesting region-selective conversion phenomenon between sulfoxidation and H-atom abstraction was revealed in the course of the oxidation reaction of dimethylsulfide. The combined experimental and theoretical study on the elucidation of the intrinsic reactivity patterns of the HRP-I and HRP-II mimics provides a valuable tool for evaluating the particular role of the HRP active species in biological systems.
- A novel tetramethylpyrazine bis-nitrone (TN-2) protects against 6-hydroxyldopamine-induced neurotoxicity via modulation of the NF-κB and the PKCα/PI3-k/akt pathways. [JOURNAL ARTICLE]
- Neurochem Int 2014 Sep 9.
The natural product tetramethylpyrazine (TMP) has a variety of biologic activities, including neuroprotection. Nitrones are powerful free radical scavengers. We have designed and synthesized a TMP derivative, TN-2, which is armed with two nitrone moieties.In this study, we investigated the neuroprotective effect of TN-2 against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in zebrafish.PC12 cells, zebrafish and rats were exposed to 6-OHDA challenge. MTT assay, LDH release, Hoechst staining, DAF-FM staining, luciferase reporter construct transfection, and western blotting were applied to detect cell viability, apoptosis, intracellular nitric oxide (NO), NF-κB transcriptional activity and proteins expression. In zebrafish, whole-mount staining and real-time PCR were performed to quantify dopaminergic neurons and mRNA expression. Hemotoxilin and eosin staining and immunohistochemistry for glial fibrillary acidic protein were used to detect the astrocyte activation in the unilateral 6-OHDA rat model.TN-2 but not TMP exhibited potent neuroprotective effect against 6-OHDA-induced apoptosis in PC12 cells. Moreover, TN-2 prevented dopaminergic neuron loss and suppressed mRNA expression of pro-inflammatory genes, including IL-1β, TNF-α and COX-2, in 6-OHDA-treated zebrafish. TN-2 remarkably attenuated microglial/astrocyte activation in the unilateral 6-OHDA rat model. The mechanistic study demonstrated that TN-2 inhibited over-production of intracellular NO and protein expression of inducible nitric oxide synthase through down-regulating NF-κB activity. Additionally, the PKCα/PI3-K/Akt pathway was also involved in the neuroprotection of TN-2.These results suggest that TN-2 protected against 6-OHDA-induced neurotoxicity via modulating the NF-κB-medicated neuroinflammation and PKCα/PI3-K/Akt pathways.
- Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. [JOURNAL ARTICLE]
- Cell Tissue Res 2014 Sep 12.
Mesenchymal stem cell (MSC) therapy is promising for neuroprotection but there is no report of an appropriate in vitro model mimicking the situation of the in vivo retina that is able to test the effect of MSCs in suspension or encapsulated with/without a drug combination. This study aims to establish a viable mixed co-culture model having three layers: neuroretina explants (NRs), retinal pigment epithelium (RPE) cells and adipose tissue-derived MSCs (AT-MSCs) for evaluating adipose-MSC effects. AT-MSCs were grown on the lower surface of a transwell membrane and RPE cells were grown on the bottom of a culture plate as monocultures. A transwell membrane was inserted into a culture plate well. NR was placed as an organotypic culture on the upper surface of the transwell membrane. Thus, a triple-layered co-culture setup was constructed. In double-layered setups, NR were co-cultured with AT-MSCs or RPE cells. Optimum medium, experiment execution period and transwell membrane permeability (TMP) were determined. MSC effects on RPE cell proliferation and NR reactive gliosis were evaluated. Limitations were discussed. Our study shows that neurobasal A with DMEM (1:1) mixed medium was suitable for viability of all three layers. AT-MSC growth decreased TMP significantly, 30-60 % in 3- to 6-day periods. Spontaneous NR reactive gliosis limits the experiment execution period to 6 days. AT-MSCs maintained their undifferentiated nature and showed no or limited neuroprotective effects. In this study, we successfully assembled viable double- and triple-layered co-culture setups for AT-MSCs, RPE and NR, optimised conditions for their survival and explored setup Limitations.
- [Identification of metabolites of antitumor lead compound T-OA in rat urine by HPLC-HRMS]. [English Abstract, Journal Article]
- Zhongguo Zhong Yao Za Zhi 2014 Mar; 39(5):911-5.
To study the major metabolites of antitumor lead compound T-OA (oleanolic acyl-3, 5, 6-trimethyl pyrazine-2-methyl ester) in rat urine, in order to preliminarily infer its metabolic mode in rats.Rat urines of the blank group, the raw material group (ligustrazine TMP and oleanolic acid OA Moore equivalent) and the T-OA group were collected and freeze-dried; Solids were extracted by ethyl acetate; And then the extracts were re-dissolved with acetonitrile. HPLC-HRMS coupling technique was adopted to find the potential mass spectrum peak under ESI(+) (see symbol) ESI(-) modes. Metabolite-related information was obtained by comparing the three groups of spectra.One metabolite of OA and two metabolites of TMP were identified in the raw material group; none metabolite of T-OA but one phase II metabolite was detected in the T-OA group.It is the first time to identify one phase II metabolite of T-OA and one phase II metabolite of OA were identified in rat urine. On that basis, the researchers preliminarily inferred that T-OA does not show the efficacy in the form of raw material. The HPLC-HRMS method established could be used to identify metabolites of related derivative structures. This paper could also provide certain reference for designing pro-drugs based on oleanolic acid.
- Association of serum levels of FGF23 and alpha-Klotho with glomerular filtration rate and proteinuria among cardiac patients. [JOURNAL ARTICLE]
- BMC Nephrol 2014 Sep 8; 15(1):147.
Expression and/or excretion of fibroblast growth factor-23 (FGF23) and its co-receptor Klotho are altered in patients with end-stage renal disease. The possibility that the FGF23/alpha-Klotho system mediates the aggravated cardiovascular outcome among patients with chronic kidney disease (CKD) has been suggested. We determined whether FGF23 and alpha-Klotho concentrations are altered among patients with reduced renal function and proteinuria.Serum FGF23 and alpha-Klotho were measured in cardiology patients who were not undergoing chronic hemodialysis. Estimated glomerular filtration rate (eGFR) was correlated negatively with FGF23 and positively with alpha-Klotho.The correlation between FGF23 and the renal tubular maximum reabsorption rate of phosphate to the GFR (TmP/GFR) was not significant, but that between FGF23 and serum calcium or inorganic phosphate was significant among patients with an estimated GFR of less than 60 mL/min/m2. By stepwise multivariate regression analysis, eGFR was selected as significant predictor for FGF23 or alpha-Klotho among patients with an estimated GFR of less than 60 mL/min/m2; however, urine albumin/creatinine ratio was not selected as a predictor for FGF23 or alpha-Klotho irrespective of the eGFR levels. In patients with eGFR of <60 mL/min/1.73 m2, UACR was significantly associated with log(FGF23); but, this association did not remain statistically significant in a multivariate model.Among cardiology patients with various stages of CKD, serum concentrations of FGF23 and alpha-Klotho were associated with renal function, but not with the extent of proteinuria.
- Fibroblast Growth Factor 23, but not Parathyroid Hormone, Is Associated With Urinary Phosphate Regulation in Patients on Peritoneal Dialysis. [JOURNAL ARTICLE]
- Ther Apher Dial 2014 Sep 4.
Fibroblast growth factor (FGF) 23 plays an important role in regulation of renal phosphate excretion in patients with chronic kidney disease. However, it remains undetermined whether FGF23 is closely linked to renal phosphate handling in patients with low glomerular filtration rate (GFR). The present cross-sectional study included 52 outpatients undergoing peritoneal dialysis with urine volume ≥ 100 mL/day. The primary outcome was level of urinary phosphate excretion, and the secondary outcomes were tubular maximal reabsorption of phosphate normalized to GFR (TmP/GFR), an index of the renal threshold for phosphate excretion, and level of peritoneal phosphate excretion. Variates of interest were serum FGF23 and parathyroid hormone (PTH) levels. The median and interquartile range of serum FGF23 level, TmP/GFR, and total urinary and peritoneal phosphate excretion were 5610 (1493-11 430) ng/mL, 1.30 (0.44-1.86) mg/dL, 117 (40-234) mg/day, and 208 (156-250) mg/day, respectively. Multivariate linear regression analysis revealed that serum FGF23 level was significantly (P < 0.05) associated with TmP/GFR negatively and significantly (P < 0.05) associated with urinary phosphate excretion positively, even after adjusting for confounders. In contrast, none of the three outcome variates was associated with serum PTH level. Neither serum FGF23 nor PTH level was associated with peritoneal phosphate excretion. The present study indicates that FGF23, but not PTH, is involved in urinary phosphate regulation, even in patients on peritoneal dialysis with residual renal function.
- [Determination of sulfonamide potentiators in animal origin foods by ultra performance liquid chromatography-tandem mass spectrometry]. [English Abstract, Journal Article]
- Se Pu 2014 May; 32(5):524-8.
A method for the determination of sulfonamide potentiators, trimethoprim (TMP), diaveridine (DVD) and ormetoprin (OMP), in different animal origin food matrices (including chicken muscle, fish muscle, chicken liver, egg and milk) has been developed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample was extracted by formic acid-acetonitrile (1:9, v/v), cleaned-up by hexane, separated on an Acquity UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) with gradient elution. The determination was carried out with electrospray ion source under the positive mode and multiple reaction monitoring (MRM) mode. The extraction recoveries of three extraction solvents were observed. The purification condition and concentration condition were optimized. In addition, the mobile phase, column temperature and solid phase extraction column were studied. The calibration curves showed a good linearity in the range of 1.25-30.0 microg/L, and the correlation coefficients (r) were higher than 0.99. The limits of quantification (LOQ, S/N = 10) of the three potentiators were 5.0 microg/kg. At the spiked levels of 5.0, 10.0 and 20.0 microg/kg, the recoveries of the three potentiators were ranged from 61.2% to 108.5%, and the relative standard deviations (RSD, n = 6) ranged from 1.1% to 9.8%. The results indicate that the method is simple, rapid, sensitive and suitable for the qualitative and quantitative analysis of the three potentiators in multiple matrices.