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- Genotypic characterization of Streptococcus pneumoniae serotype 19F in Malaysia. [JOURNAL ARTICLE]
- Infect Genet Evol 2013 Dec 13.
Streptococcus pneumoniae is an epidemiologically important bacterial pathogen. Recently, we reported the antibiotic susceptibility patterns of a limited collection of pneumococcal isolates in Malaysia with a high prevalence of erythromycin resistant strains. In the present study, 55 of the pneumococcal isolates of serotype 19F were further analysed by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The generated genotypic patterns were then correlated with the antibiograms previously reported. Forty-seven different PFGE profiles (PTs) were obtained, showing that the isolates were genetically diverse. MLST identified 16 sequence types (STs) with ST-236 being predominant (58.2%), followed by ST-81 (10.3%). Among the ST-236 isolates, 22 were erythromycin resistant S. pneumoniae (ERSP) and 15 were trimethoprim/sulfamethoxazole (TMP/SMX) resistant, while among ST-81, four isolates were ERSP and two were TMP/SMX resistant. The high prevalence of erythromycin resistant serotype 19F isolates of ST-236 in this study has also been reported in other North and South East Asian countries.
- Micropit surfaces designed for accelerating osteogenic differentiation of murine mesenchymal stem cells via enhancing focal adhesion and actin polymerization. [JOURNAL ARTICLE]
- Biomaterials 2013 Dec 13.
Recent reports demonstrate that enhanced focal adhesion (FA) between cells and the extracellular matrix (ECM) and intracellular actin polymerization (AP) upregulates cellular functions such as proliferation, stem-cell fate and differentiation. Purposed to accelerate osteogenic differentiation, enhancement of FAs and AP of cells was induced by adding a tailor-made micropit (tMP, 3 × 3 μm(2)) with different heights (2 or 4 μm). The tMP surface was examined for its differentiation efficiency using mouse mesenchymal stem cells, C3H10T1/2. Though the cell spreading area was not affected by the surface topography, cells on the tMP substrates had enhanced FAs which were significantly confined inside the micropits, increased actin polymerization and traction forces, and osteogenic differentiation. Further experiments with Y-27632 and Blebbistatin, which specifically regulate FA or AP functions, demonstrated that the tMP-induced acceleration of osteogenic differentiation was caused by the rho-associated, coiled-coil containing protein kinase (ROCK) and nonmuscle myosin II (NM II), which are key molecules of the RhoA/ROCK signaling pathway. The tMP is applicable as an osteo-active substrate for the instructive bone cell differentiation and population.
- 2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and inflammation in a UVA-induced melanoma/keratinocytes co-culture system. [JOURNAL ARTICLE]
- Int Immunopharmacol 2013 Dec 10.
2,3,5,6-Tetramethylpyrazine (TMP) is known as a composition of Ephedra sinica and it has been used in the treatment of several disorders such as asthma, heart failure, rhinitis, and urinary incontinence. It has been reported that TMP inhibits melanoma metastasis and suppression angiogenesis by VEGF.The inhibitory activity of melanogenic proteins by TMP was confirmed in UVA-induced melanoma/keratinocyte co-culture system in this paper.The melanin content, cell viability and cytokines release such as TNFα, IL-1β, IL-8 and GM-CSF were measured by ELISA assay. In addition, TRP1, MITF and MAPK signaling protein expression were also evaluated by Western blotting analysis.Decreasing melanogenic factors (TRP1, MITF, and MAPK) and factors (TNFα, IL-1β, IL-8, and GM-CSF) improving skin cancer and inflammation were identified.It suggests that TMP can serve as a potent candidate for regulation of melanogenesis.
- 2,2,6,6-Tetramethylpiperidine-Catalyzed, Ortho-Selective Chlorination of Phenols by Sulfuryl Chloride. [JOURNAL ARTICLE]
- J Org Chem 2013 Dec 13.
2,2,6,6-tetramethylpiperidine (TMP)-catalyzed (1-10%) chlorinations of phenols by SO2Cl2 in aromatic solvents are more ortho-selective than with primary and less hindered secondary amine catalysts. Ortho-selective chlorination is successful even with electron deficient phenols such as 2-hydroxybenzaldehyde and 2'-hydroxyacetophenone. Notably, ortho selectivity increases with the reaction temperature. On the other hand, tetraalkylammonium chloride catalyzed chlorinations are moderately para-selective.
- Congenital taurine deficiency in mice is associated with reduced sensitivity to nociceptive chemical stimulation. [JOURNAL ARTICLE]
- Neuroscience 2013 Dec 6.
The amino acid taurine is required for development and functioning of the central and peripheral nervous system where it exerts osmoregulatory, neuromodulatory and anti-apoptotic actions. It is subject to cellular import by the taurine transporter slc6a6. Absence of the transporter and consequently, absence of taurine leads to several neurologic deficits and sensory losses. In a slc6a6 knockout mouse model, consequences of congenital taurine deficiency were assessed in nociceptive sensory processes. The formalin assay, hot plate assay, and summated generator potentials in response to local nociceptive stimulation with gaseous CO2 were applied. Reduced responsiveness of slc6a6(-/-) mice to nociceptive stimulation was observed in particular to chemical nociceptive stimuli. Scl6a6 knockout mice spent significantly less time licking the formalin injected paw and displayed smaller amplitudes of the nociceptive nasal mucosa potentials than wild type mice (p = 0.002 and 0.01 respectively). In contrast, withdrawal latencies on a hot plate did not significantly differ, suggesting that intracellular taurine deficits lead in particular to a hyposensitivity of nociceptive sensory neurons sensitive to noxious chemical stimulation. As hereditary absence of taurine affects biological processes of anatomical structure development, the altered nociceptive responses likely reflect consequences of compromised peripheral nervous system development.
- Urinary Tract Infections due to Multidrug-Resistant Enterobacteriaceae: Prevalence and Risk Factors in a Chicago Emergency Department. [Journal Article]
- Emerg Med Int 2013.:258517.
Background.Selection of empiric antibiotics for urinary tract infections (UTIs) has become more challenging because of the increasing rates of multidrug-resistant Enterobacteriaceae (MDRE) infections. Methods. This retrospective study was conducted to determine antibiotic resistance patterns, risk factors, and appropriate empiric antibiotic selection for MDRE UTIs. Adult patients seen in the Emergency Department (ED) with Enterobacteriaceae UTIs during 2008-2009 were identified from review of microbiology records. MDRE were defined as organisms resistant to at least 3 categories of antibiotics.
Results.There were 431 eligible patients; 83 (19%) had MDRE UTIs. Resistance rates for individual antibiotics among MDRE UTIs were significantly greater than non-MDRE UTIs: levofloxacin, 72% versus 14%; TMP-SMX, 77% versus 12%; amoxicillin-clavulanate, 35% versus 4%; nitrofurantoin, 21% versus 12%, and ceftriaxone, 20% versus 0%. All Enterobacteriaceae isolates were susceptible to ertapenem (MIC ≤ 2 mg/L). Independent risk factors for MDRE UTI were prior fluoroquinolone use within 3 months (adjusted odds ratio (aOR) 3.64; P = 0.001), healthcare-associated risks (aOR 2.32; P = 0.009), and obstructive uropathy (aOR 2.22; P = 0.04).
Conclusion.Our study suggests that once-daily intravenous or intramuscular ertapenem may be appropriate for outpatient treatment of ED patients with MDRE UTI.
- Occurrence and removal of six pharmaceuticals and personal care products in a wastewater treatment plant employing anaerobic/anoxic/aerobic and UV processes in Shanghai, China. [JOURNAL ARTICLE]
- Environ Sci Pollut Res Int 2013 Dec 5.
The occurrence and removal of six pharmaceuticals and personal care products (PPCPs) including caffeine (CF), N, N-diethyl-meta-toluamide (DEET), carbamazepine, metoprolol, trimethoprim (TMP), and sulpiride in a municipal wastewater treatment plant (WWTP) in Shanghai, China were studied in January 2013; besides, grab samples of the influent were also taken every 6 h, to investigate the daily fluctuation of the wastewater influent. The results showed the concentrations of the investigated PPCPs ranged from 17 to 11,400 ng/L in the WWTP. A low variability of the PPCP concentrations in the wastewater influent throughout the day was observed, with the relative standard deviations less than 25 % for most samples. However, for TMP and CF, the slight daily fluctuation still reflected their consumption patterns. All the target compounds except CF and DEET, exhibited poor removal efficiencies (<40 %) by biological treatment process, probably due to the low temperature in the bioreactor, which was unfavorable for activated sludge. While for the two biodegradable PPCPs, CF, and DEET, the anaerobic and oxic tank made contributions to their removal while the anoxic tank had a negative effect to their elimination. The tertiary UV treatment removed the investigated PPCPs by 5-38 %, representing a crucial polishing step to compensate for the poor removal by the biologic treatment process in winter.
- Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum. [Journal Article]
- J Anal Methods Chem 2013.:297285.
A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a Hibar μ Bondapak ODS C18 column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method.
- Bleeding events following concurrent use of warfarin and oseltamivir by medicare beneficiaries. [Journal Article]
- Ann Pharmacother 2013 Nov; 47(11):1420-8.
During the 2009 H1N1 influenza pandemic, the UK Medicines and Healthcare Products Regulatory Agency received case reports suggesting a potentiation of warfarin anticoagulation by the antiviral drug oseltamivir. We evaluated this putative interaction using Medicare data.To determine the frequency of bleeding following addition of oseltamivir or comparator drugs among Medicare beneficiaries taking warfarin.This was a retrospective cohort evaluation using Medicare nationwide data. Cohort members were Medicare Parts A, B, and D beneficiaries from June 30, 2006 to October 31, 2010 receiving warfarin for at least 1 month prior to a concomitant drug of interest (oseltamivir, ampicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and angiotensin-converting enzyme (ACE) inhibitors). Bleeding within 14 days of new prescriptions for oseltamivir or comparators was identified using inpatient or emergency department ICD-9 (International Classification of Diseases, ninth revision) discharge diagnosis codes for gastrointestinal hemorrhage, epistaxis, hematuria, and intracranial bleeding. Patients with bleeding within 30 days preceding the prescription concomitant to warfarin were excluded.With concomitant ACE inhibitors as reference, adjusted odds ratios (ORs) for any bleeding events within 14 days were 1.47 (95% confidence interval [CI] = 1.08-1.88), 1.24 (95% CI = 0.97-1.57), and 2.74 (95% CI = 2.53-3.03), for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively. In a sensitivity analysis, adjusted ORs over a 7-day period were 1.89 (95% CI = 1.29-2.59), 1.47 (95% CI = 1.06-2.02), and 3.07 (95% CI = 2.76-3.49) for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively.Bleeding with oseltamivir plus warfarin was not significantly increased over a 14-day observation period; a sensitivity analysis showed a statistically significant increase over a 7-day period; in contrast, the data consistently showed the known tendency of TMP-SMX to potentiate the effects of warfarin. The results should be interpreted with the limitations of this approach in mind, including the inability to control for unmeasured confounders.
- Virgin coconut oil protects against liver damage in albino rats challenged with the anti-folate combination, trimethoprim-sulfamethoxazole. [JOURNAL ARTICLE]
- J Basic Clin Physiol Pharmacol 2013 Nov 28.:1-5.
Abstract Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad-spectrum antibiotic. However, its use is associated with toxic reactions. Virgin coconut oil (VCO), derived from coconut, has been widely used throughout history for its medicinal value. The aim of this study was to investigate the beneficial actions of VCO against TMP-SMX-induced alterations in serum biochemical end points. Methods: Twenty rats were divided into four groups. Group 1 (control) received no drug, whereas group 2 received TMP-SMX (8/40 mg/kg) twice daily for 7 days. Group 3 was administered coconut oil at a dose of 600 mg/kg body weight per day. The last group was treated with TMP-SMX (8/40 mg/kg) and coconut oil (600 mg/kg) simultaneously. Blood samples were collected from all groups on the 8th day of the experiment for measurement of serum biochemical parameters. Organ weights and coefficients were also evaluated. Results: TMP-SMX caused a significant (p<0.05) increase in the levels of serum total bilirubin, lactate dehydrogenase, and alkaline phosphatase by 192%, 67%, and 41%, respectively, relative to controls. This was followed by a significant reduction in triglyceride and relative kidney weight by 40% and 7%, respectively. There were no significant differences (p>0.05) in the activities of serum aminotransferases, total acid phosphatase, γ-glutamyl transferase, uric acid, cholesterol, albumin, and urea levels. Supplementation of VCO ameliorated TMP-SMX-induced effects by restoring the levels of total bilirubin, alkaline phospahatase, and lactate dehydrogenase. Conclusions: The results of this study demonstrate that the active components of coconut oil had protective effects against the toxic effects induced by TMP-SMX administration, especially in the liver of rats.