Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Enzymatic synthesis of poly(catechin)-antibiotic conjugates: an antimicrobial approach for indwelling catheters. [JOURNAL ARTICLE]
- Appl Microbiol Biotechnol 2014 Oct 21.
Biofilm formation in urinary indwelling catheters is one of the most critical issues that patients face. Catheters were coated with poly(catechin)-antibiotic conjugates with enhanced antimicrobial properties. Catechin was conjugated with two antibiotics, namely trimethoprim (TMP) and sulfamethoxazole (SMZ) via activation with N,N'-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing α-amine moieties. Silicone and polyurethane catheters were functionalized in situ through laccase oxidation of catechin-antibiotic conjugates. Four antimicrobial coatings were produced, namely with poly(catechin), poly(catechin)-TMP, poly(catechin)-SMZ and poly(catechin)-TMP-SMZ. The bacterial adhesion reduction was tested on the functionalized devices using gram-negative and gram-positive strains. The most significant reduction in adhesion was observed with poly(catechin)-TMP (gram-negative -85 % and gram-positive -87 %) and with poly(catechin)-TMP-SMZ (gram-negative -85 % and gram-positive -91 %). The cytotoxicity to mammalian cells was tested by indirect contact for 5 days and revealed that all the tested coatings supported more than 90 % of viable cells. A promising approach for the increase of the indwelling catheter lifespan was developed aiming to reduce catheter-associated chronic infections.
- Effects of filtration modes on membrane fouling behavior and treatment in submerged membrane bioreactor. [JOURNAL ARTICLE]
- Bioresour Technol 2014 Sep 20.:391-395.
Relaxation or backwashing is obligatory for effective operation of membrane module and intermittent aeration is helpful for nutrients removal. This study was performed to investigate effects of different filtration modes on membrane fouling behavior and treatment in membrane bioreactor (MBR) operated at three modes i.e., 12, 10 and 8min filtration and 3, 2, and 2min relaxation corresponding to 6, 5 and 4cycles/hour, respectively. Various parameters including trans-membrane pressure, specific cake resistance, specific oxygen uptake rate, nutrients removal and sludge dewaterability were examined to optimize the filtration mode. TMP profiles showed that MBR(8+2) with 8min filtration and 2min relaxation reduced the fouling rate and depicted long filtration time in MBR treating synthetic wastewater. MBR(12+3) was more efficient in organic and nutrients removal while denitrification rate was high in MBR(8+2).
- Isolation and antibiotic susceptibility of Shigella species from stool samples among hospitalized children in Abadan, Iran. [Journal Article]
- Gastroenterol Hepatol Bed Bench 2014; 7(4):218-23.
The aim of this study was to determine the incidence of Shigella species and their antimicrobial susceptibility patterns in hospitalized children with Shigellosis in Abadan, Iran.Shigellosis is caused by different species of Shigella and one of the most common causes of diarrhea in children. This disease is endemic in many developing countries including Iran.This prospective cross sectional study was conducted in a teaching hospital in Abadan, Iran during June 2011 to May 2013. Stool specimens were collected from pediatric age group. All isolates were confirmed as Shigella species by biochemical and serologic tests. Antibiotic sensitivity pattern of these isolates was studied by disk diffusion Method.Among all 705 stool samples, 36 (5.1%) yielded Shigella. Of cases, 392 (55.6%) were girl and 313 (44.4%) were boy. The most common Shigella isolates were S. flexneri (n=19, 52.7%) followed by S. sonnei (n=11, 30.5%), S. boydii (n=4, 11.1%) and S. dysenteriae 2(5.5%). Of the Shigella isolates, 47.2% showed resistance to two or more antimicrobial agents. Resistance pattern against various antimicrobials were as follows: trimethoprim-sulphamethoxazole (80.5%), ampicillin (63.8%), tetracycline (58.3%), chloramphenicol (33.3%), nalidixic acid (27.7%), and cefixime (16.6%). There was no resistance against ciprofloxacin and ceftriaxone.The most common isolates were S. flexneri followed by S. Sonnei. There was no antibiotic resistance against ciprofloxacin and ceftriaxone. TMP-SMZ showed highest resistance pattern.
- Efficacy of caspofungin, a 1,3-β-D-glucan synthase inhibitor, on Pneumocystis carinii pneumonia in rats. [JOURNAL ARTICLE]
- Med Mycol 2014 Oct 6.
Pneumocystis carinii pneumonia (PcP) is a common and potentially fatal opportunistic infection in immunosuppressed patients, and the standard trimethoprim-sulfamethoxazole (TMP-SMZ) treatment has serious side effects. The cell wall of the causative fungal pathogen is enriched in 1-3-β-D-glucan, providing an alternative therapeutic target. We directly compared the efficacy of the 1,3-β-D-glucan synthase inhibitor caspofungin to TMP-SMZ for promoting survival and reducing lung cyst number during the early phase of treatment in a rat model of PcP. Rats were immunosuppressed using dexamethasone for 8 weeks and PcP infection confirmed in test animals by lung print smear. The remaining rats were randomly divided into three control groups, a baseline group and two observed for 7 or 14 days, two caspofungin groups treated intravenously for 7 or 14 days (1 mg/kg/d), and 2 TMP-SMZ positive control groups treated by oral gavage for 7 or 14 days (300 mg/kg/d). Mortality was markedly reduced by both caspofungin and TMP-SMZ after 14 days (caspofungin: 20.0%, TMP-SMZ: 13.3%, Control: 40.0%). Body weight gain in caspofungin-treated rats after 7 (3.04 ± 3.54%) and 14 (4.27 ± 2.79%) days was similar to that in TMP-SMZ-treated rats (3.35 ± 1.88% and 5.85 ± 2.78%, respectively), whereas untreated controls showed weight loss. Lung weight to body weight ratio, and mean cyst number per 50 microscopic fields were significantly lower (all P < 0.05) in caspofungin-treated rats than untreated controls at both 7 and 14 days, and similar to those in the TMP-SMZ-treated rats (all P > 0.05 vs. caspofungin). Caspofungin exhibited similar efficacy to TMP-SMZ for enhancing survival and reducing lung edema and cyst load in a rat model of PcP, suggesting potential clinical utility against PcP.
- Crystal structures of Klebsiella pneumoniae dihydrofolate reductase bound to propargyl-linked antifolates reveal features for potency and selectivity. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Oct 6.
Resistance to the antibacterial antifolate trimethoprim (TMP) is increasing in Enterobacteriaceae, driving the design of next-generation antifolates effective against these Gram-negative pathogens. The propargyl-linked antifolates are potent inhibitors of dihydrofolate reductase (DHFR) from several TMP-sensitive and -resistant species, including Klebsiella pneumoniae. Recently, we have determined that these antifolates inhibit the growth of strains of K. pneumoniae, some with MIC values of 1 μg/mL. In order to further the design of potent and selective antifolates against Enterobacteriaceae, we determined the first crystal structures of K. pneumoniae DHFR bound to two of the propargyl-linked antifolates. These structures highlight that interactions with Leu 28, Ile 50, Ile 94 and Leu 54 are necessary for potency; comparison with structures of human DHFR bound to the same inhibitors reveal differences in residues (N64E, P61G, F31L and V115I) and loop conformations (residues 49-53) that may be exploited for selectivity.
- Enhanced Photoproduction of Hydrogen Peroxide by Humic Substances in Presence of Phenol Electron Donors. [JOURNAL ARTICLE]
- Environ Sci Technol 2014 Oct 6.
Addition of a series of phenol electron donors to solutions of humic substances (HS) Addition of a series of phenol electron donors to solutions of humic substances (HS) enhanced substantially the initial rates of hydrogen peroxide (H2O2) photoproduction (RH2O2), with enhancement factors (EF) ranging from a low of ~3 for 2,4,6-trimethylphenol (TMP) to a high of ~15 for 3,4-dimethoxyphenol (DMOP). The substantial inhibition of the enhanced RH2O2 following borohydride reduction of the HS, as well as the dependence of RH2O2 on phenol and dioxygen concentrations are consistent with a mechanism in which the phenols react with the triplet excited states of (aromatic) ketones within the HS to form initially a phenoxy and ketyl radical. The ketyl radical then reacts rapidly with dioxygen to regenerate the ketone and form superoxide (O2-), which subsequently dismutates to H2O2. However, as was previously noted for the photosensitized loss of TMP, the incomplete inhibition of the enhanced RH2O2 following borohydride reduction suggests that there may remain another pool of oxidizing triplets. The results demonstrate that H2O2 can be generated through an additional pathway in presence of sufficiently high concentrations of appropriate electron donors through reaction with the excited triplet states of aromatic ketones and possibly of other species such as quinones. However, in some cases, the much lower ratio of H2O2 produced to phenol consumed suggests that secondary reactions could alter this ratio significantly.
- Improving Trichoderma reesei Cel7B Thermostability by Targeting the Weak Spots. [JOURNAL ARTICLE]
- J Chem Inf Model 2014 Oct 6.
For proteins that denature irreversibly, the denaturation is typically triggered by a partial unfolding, followed by a permanent change (e.g., aggregation). The regions that initiate the partial unfolding are named "weak spots". In this work, a molecular dynamics (MD) simulation and data analysis protocol is developed to identify the weak spots of Trichoderma reesei Cel7B, an important endoglucanase in cellulose hydrolysis, through assigning the local melting temperature (Tmp) to individual residue pairs. To test the predicted weak spots, a total of eight disulfide bonds were designed in these regions and all enhanced the enzyme thermostability. The increased stability, quantified by ΔT50 (which is the T50 difference between the mutant and the wild type enzyme), is negatively correlated with the MD-predicted Tmp, demonstrating the effectiveness of the protocol and highlighting the importance of the weak spots. Strengthening interactions in these regions proves to be a useful strategy in improving the thermostability of Tr. Cel7B.
- Susceptibility of clinical Moraxella catarrhalis isolates in British Columbia to six empirically prescribed antibiotic agents. [Journal Article]
- Can J Infect Dis Med Microbiol 2014 May; 25(3):155-8.
Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance.To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin-clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole.A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E-strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines.All isolates were sensitive to amoxicillin-clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 μg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility.The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada.Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.
- In-situ biofilm characterization in membrane systems using Optical Coherence Tomography: Formation, structure, detachment and impact of flux change. [JOURNAL ARTICLE]
- Water Res 2014 Sep 16.:243-254.
Biofouling causes performance loss in spiral wound nanofiltration (NF) and reverse osmosis (RO) membrane operation for process and drinking water production. The development of biofilm formation, structure and detachment was studied in-situ, non-destructively with Optical Coherence Tomography (OCT) in direct relation with the hydraulic biofilm resistance and membrane performance parameters: transmembrane pressure drop (TMP) and feed-channel pressure drop (FCP). The objective was to evaluate the suitability of OCT for biofouling studies, applying a membrane biofouling test cell operated at constant crossflow velocity (0.1 m s(-1)) and permeate flux (20 L m(-2)h(-1)). In time, the biofilm thickness on the membrane increased continuously causing a decline in membrane performance. Local biofilm detachment was observed at the biofilm-membrane interface. A mature biofilm was subjected to permeate flux variation (20 to 60 to 20 L m(-2)h(-1)). An increase in permeate flux caused a decrease in biofilm thickness and an increase in biofilm resistance, indicating biofilm compaction. Restoring the original permeate flux did not completely restore the original biofilm parameters: After elevated flux operation the biofilm thickness was reduced to 75% and the hydraulic resistance increased to 116% of the original values. Therefore, after a temporarily permeate flux increase the impact of the biofilm on membrane performance was stronger. OCT imaging of the biofilm with increased permeate flux revealed that the biofilm became compacted, lost internal voids, and became more dense. Therefore, membrane performance losses were not only related to biofilm thickness but also to the internal biofilm structure, e.g. caused by changes in pressure. Optical Coherence Tomography proved to be a suitable tool for quantitative in-situ biofilm thickness and morphology studies which can be carried out non-destructively and in real-time in transparent membrane biofouling monitors.
- Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma. [Journal Article]
- Biomark Res 2014.:16.
Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations.Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses.Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1-2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles.This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1-2. Extended dosing of romidepsin can be tolerated in responding patients.NCT00426764,NCT00106431.