29 research outputs found
Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection
ABSTRACT
The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant
Enterobacteriaceae
. We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant
Escherichia coli
and
Klebsiella
spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and
fumC-fimH
(
E. coli
) or
tonB
(
Klebsiella pneumoniae
) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with
E. coli
sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.
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Conformational Ensembles and Sampled Energy Landscapes: Analysis and Comparison
We present novel algorithms and software addressing four core problemsin computational structural biology, namely analyzing a conformationalensemble, comparing two conformational ensembles, analyzing a sampledenergy landscape, and comparing two sampled energy landscapes. Usingrecent developments in computational topology, graph theory, andcombinatorial optimization, we make two notable contributions. First,we a present a generic algorithm analyzing height fields. We then usethis algorithm to perform density based clustering of conformations,and to analyze a sampled energy landscape in terms of basins andtransitions between them. In both cases, topological persistence isused to manage ruggedness. Second, we introduce two algorithms tocompare transition graphs. The first is the classical earth mover distance metric which depends only on local minimum energyconfigurations along with their statistical weights, while the secondincorporates topological constraints inherent to conformationaltransitions.Illustrations are provided on a simplified protein model (BLN69), whosefrustrated potential energy landscape has been thoroughly studied.The software implementing our tools is also made available, and shouldprove valuable wherever conformational ensembles and energy landscapesare used
Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats.
Cerebral stroke is the leading cause of death and permanent disability among elderly people. In both humans and animals, cerebral ischemia damages the nerve cells in vulnerable regions of the brain, viz., hippocampus, cerebral cortex, cerebellum, and hypothalamus. The present study was conducted to evaluate the therapeutic efficacy of nanoencapsulated quercetin (QC) in combating ischemia-reperfusion-induced neuronal damage in young and aged Swiss Albino rats. Cerebral ischemia was induced by occlusion of the common carotid arteries of both young and aged rats followed by reperfusion. Nanoencapsulated quercetin (2.7 mg/kg b wt) was administered to both groups of animals via oral gavage two hours prior to ischemic insults as well as post-operation till day 3. Cerebral ischemia and 30 min consecutive reperfusion caused a substantial increase in lipid peroxidation, decreased antioxidant enzyme activities and tissue osmolality in different brain regions of both groups of animals. It also decreased mitochondrial membrane microviscosity and increased reactive oxygen species (ROS) generation in different brain regions of young and aged rats. Among the brain regions studied, the hippocampus appeared to be the worst affected region showing increased upregulation of iNOS and caspase-3 activity with decreased neuronal count in the CA1 and CA3 subfields of both young and aged rats. Furthermore, three days of continuous reperfusion after ischemia caused massive damage to neuronal cells. However, it was observed that oral treatment of nanoencapsulated quercetin (2.7 mg/kg b wt) resulted in downregulation of iNOS and caspase-3 activities and improved neuronal count in the hippocampal subfields even 3 days after reperfusion. Moreover, the nanoformulation imparted a significant level of protection in the antioxidant status in different brain regions, thus contributing to a better understanding of the given pathophysiological processes causing ischemic neuronal damage
Physicochemical Studies on the Micellization of Cationic, Anionic, and Nonionic Surfactants in Water–Polar Organic Solvent Mixtures
The
effect of cosolvent (ethane-1,2-diol and dimethyl sulfoxide)
on the self-assembly of three surfactants, <i>N</i>,<i>N</i>,<i>N</i>-trimethyl-1-dodecanaminium bromide
(DTAB), sodium [dodecanoylÂ(methyl)Âamino]Âacetate (SDDS), and polyoxyethylene
(20) sorbitan monolaurate (Tween-20) in aqueous solution have been
investigated by conductometric, tensiometric, and viscometric techniques
at 298 K. The main focus was on the effect of solvent on critical
micelle concentration (cmc), free energy contribution to micellization
(Δ<i>G</i><sub>m</sub><sup>0</sup>), tail transfer Gibbs free energy (Δ<i>G</i><sub>trans</sub><sup>0</sup>), Gibbs adsorption energy (Δ<i>G</i><sub>ads</sub><sup>0</sup>), and some micellar
interfacial parameters, for example, Gibbs surface excess (Γ<sub>max</sub>), minimum area per surfactant molecule (<i>A</i><sub>min</sub>), surface pressure (Î <sub>cmc</sub>), and p<i>C</i><sub>20</sub>(= −logÂ(<i>C</i><sub>20</sub>), where <i>C</i><sub>20</sub> is the surfactant molar
concentration required to reduce the surface tension of mixed solvent
by 20 mN m<sup>–1</sup>). With increasing concentration of
cosolvent in the binary mixture, the cohesive force decreases, and
surfactant molecules are more soluble in mixed solvent. As a result,
micellization process becomes less favorable, and an increase in cmc
was obtained. Steady state fluorescence spectroscopy was used to determine
the aggregation number (<i>N</i><sub>agg</sub>) of the surfactants
in organic solvent–water binary mixture and also the micropolarity
of the mixed solvent. It was observed that <i>N</i><sub>agg</sub> decreased with the increase of organic solvent concentration.
The micropolarity of the mixed solvent and packing parameter (<i>P</i>) were also determined
Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice.
BACKGROUND & OBJECTIVES: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. METHODS: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 μg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. RESULTS: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. INTERPRETATION & CONCLUSIONS: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action
Nanoencapsulation of Quercetin Enhances its Dietary Efficacy in Combating Arsenic-Induced Oxidative Damage in Liver and Brain of Rats
Aims: This study was performed to evaluate the therapeutic efficacy of nanocapsulated flavonoidal quercetin
(QC) in combating arsenic-induced reactive oxygen species (ROS)-mediated oxidative damage in hepatocytes
and brain cells in a rat model.
Main methods: Hepatic and neuronal cell damage in rats was made by a single injection (sc) of sodium
arsenite (NaAsO2, 13 mg/kg b. wt. in 0.5 ml of physiological saline). A single dose of 500 μl of quercetin
suspension (QC) (QC 8.98 μmol/kg) or 500 μl of nanocapsulated QC (NPQC) (QC 8.98 μmol/kg) was given
orally to rats at 90 min prior to the arsenite injection.
Key findings: Inorganic arsenic depositions (182±15.6 and 110±12.8 ng/g protein) were found in hepatic and
neuronal mitochondrial membranes. Antioxidant levels in hepatic and neuronal cells were reduced
significantly by arsenic. NPQC prevented the arsenite-induced reduction in antioxidant levels in the liver and
brain. Arsenic induced a substantial decrease in liver and brain cell membrane microviscosities, and NPQC
treatment resulted in a unique protection against the loss. A significant correlation between mitochondrial
arsenic and its conjugated diene level was observed both in liver and brain cells for all experimental rats.
Significance: Arsenic-specific antidotes are used against arsenic-induced toxicity. However, the target site is
poorly recognized and therefore achieving an active concentration of drug molecules can be a challenge.
Thus, our objective was to formulate NPQC and to investigate its therapeutic potential in an oral route against
arsenite-induced hepatic and neuronal cell damage in a rat mode
Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho- TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms
Nanocapsulated Curcumin: Oral Chemopreventive Formulation against Diethylnitrosamine Induced Hepatocellular Carcinoma in Rat
Toxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for
their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense
importance for their excellent anticarcinogenic activities and minimum toxic manifestations in biological
system. However, Cur is lipophilic and thus following oral administration hardly appears in blood indicating
its potential therapeutic challenge in cancer therapy. Nanocapsulated Cur has been used as a drug
delivery vector to focus the effectiveness of these vesicles against hepatocellular carcinoma. The theme of
work was to evaluate effectiveness in oral route of polylactide co-glycolide (PLGA) Nanocapsulated curcumin
(Nano Cur) against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rat.
Nano Cur of average diameter 14 nm and encapsulation efficiency of 78% were prepared. Fourier Transform
Infra Red (FTIR) analysis revealed that there is no chemical interaction between drug and the polymer.
Three i.p. injections of the chemical hepatocarcinogen DEN at 15 days interval causes hepatotoxicity,
the generation of reactive oxygen species (ROS), lipid peroxidation, decrease in plasma membrane microviscosity
and depletion of antioxidant enzyme levels in liver. Nano Cur (weekly oral treatment for
16 weeks at 20 mg/kg b.wt) in DEN induced HCC rats exerted significant protection against HCC and
restored redox homeostasis in liver cells. Nanocapsulated Cur caused cancer cell apoptosis as visualized
by ApoBrdU analysis. Histopathological analysis confirmed the pathological improvement in the liver.
Nano Cur was found to be a potential formulation in oral route in combating the oxidative damage of
hepatic cells and eliminating DEN induced hepatocellular cancer cells in rat whereas identical amount
of free Cur treatment was found almost ineffective
Effect of nanoencapsulated quercetin on GSH concentration in different brain regions of ischemia-reperfusion induced young and aged rats.
<p><b>A</b>. Normal, <b>B</b>. Ischemia-Reperfusion induced, <b>C</b>. <b>B</b>+Free QC treated, <b>D</b>. <b>B</b>+ Empty nanoparticle treated, <b>E</b>. <b>B</b>+ Nano QC treated. Values are mean ± SE of rats.</p
Anticarcinogenic Activity of Nanoencapsulated Quercetin in Combating Diethylnitrosamine-induced Hepatocarcinoma in Rats
Hepatocellular carcinoma is the most common primary
hepatic malignancy worldwide. N-Nitroso compounds act
as strong carcinogens in various animals, including
primates. Diethylnitrosamine (DEN) is a well known
carcinogenic substance, which induces hepatic carcinoma.
The theme of the study was to evaluate the therapeutic
efficacy of nanoencapsulated flavonoidal quercetin
(3,5,7,30,40-pentahydroxy flavone, QC) in combating
DEN-induced hepatocarcinogenesis in rats. DEN induced
a substantial increase in relative liver weights with
proliferation and development of hyperplastic nodules.
A significant increase in hepatocellular and nephrotoxicity
indicated by serum alkaline phosphatase, aspartate
transaminase, alanine transaminase, urea, and creatinine
was observed in DEN-treated animals. Maximum
protection from such toxicity was provided by
nanoparticulated QC. Elevated levels of conjugated
diene in DEN-treated rats were lowered significantly by
nanoparticulated QC. Antioxidant levels in hepatic
cells were reduced significantly by the induction
of DEN. Nanoparticulated QC was found most potent
for complete prevention of DEN-induced reduction
in antioxidant levels in the liver. Upregulation of
glutathione-S-transferase activity by DEN induction
was reduced maximally by nanoencapsulated QC.
Nanoencapsulated QC completely protected the
mitochondrial membrane of the liver from carcinoma
mediated by DEN injection. A significant correlation could
be drawn between DEN-induced tissue reactive oxygen
species generation and cytochrome C expression in the
liver. Nanoencapsulated QC completely prevented the
DEN-induced cytochrome C expression in the liver
significantly