Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

30 inch Roll-Based Production of High-Quality Graphene Films for Flexible Transparent Electrodes

We report that 30-inch scale multiple roll-to-roll transfer and wet chemical doping considerably enhance the electrical properties of the graphene films grown on roll-type Cu substrates by chemical vapor deposition. The resulting graphene films shows a sheet resistance as low as ~30 Ohm/sq at ~90 % transparency which is superior to commercial transparent electrodes such as indium tin oxides (ITO). The monolayer of graphene shows sheet resistances as low as ~125 Ohm/sq with 97.4% optical transmittance and half-integer quantum Hall effect, indicating the high-quality of these graphene films. As a practical application, we also fabricated a touch screen panel device based on the graphene transparent electrodes, showing extraordinary mechanical and electrical performances

Down-titration of biologics for the treatment of rheumatoid arthritis: A systematic literature review

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice

ADVERSE DRUG REACTIONS IN PEDIATRIC PATIENTS IN A TERTIARY CARE HOSPITAL IN KOLLAM

Objective: Adverse drug reactions have not been as thoroughly studied in children as they have in adults. Extrapolation of efficacy, dosing regimens, and ADRs from adult data are inappropriate owing to developmental changes in physiology and drug handling. There is a lack of local data regarding the potential risk of ADRs in pediatric patients. Objective of this study is to identify the adverse drug reaction (ADR) profile in pediatric patients. Methods: In this cross-sectional study, 450 children attending the pediatric inpatient and outpatient department were selected, and the CDSCO reporting form for suspected ADR reporting forms was collected from those who had any adverse events by the consulting pediatrician. Later, this form was analyzed for the details for ADRs and assessed for causality, severity, and preventability using Naranjo’s algorithm, Hartwig and Siegel scale, and modified Schumock and Thornton scale of adverse drug reactions. Results: The cross-sectional study revealed a prevalence of 12.89%. Antibiotics caused more ADRs than any other group of drugs. Dermatological ADRs were the most common. Most ADRs were not preventable and were of moderate severity. The causality assessment showed that most ADRs were possible category. Conclusion: The ADRs are often unrecognized. We need more strict monitoring for early detection, treatment, and more importantly prevention of these events in the future. For that, more awareness programs, CMEs and teamwork are extremely important among the caregivers

Strained graphene structures: from valleytronics to pressure sensing

Due to its strong bonds graphene can stretch up to 25% of its original size without breaking. Furthermore, mechanical deformations lead to the generation of pseudo-magnetic fields (PMF) that can exceed 300 T. The generated PMF has opposite direction for electrons originating from different valleys. We show that valley-polarized currents can be generated by local straining of multi-terminal graphene devices. The pseudo-magnetic field created by a Gaussian-like deformation allows electrons from only one valley to transmit and a current of electrons from a single valley is generated at the opposite side of the locally strained region. Furthermore, applying a pressure difference between the two sides of a graphene membrane causes it to bend/bulge resulting in a resistance change. We find that the resistance changes linearly with pressure for bubbles of small radius while the response becomes non-linear for bubbles that stretch almost to the edges of the sample. This is explained as due to the strong interference of propagating electronic modes inside the bubble. Our calculations show that high gauge factors can be obtained in this way which makes graphene a good candidate for pressure sensing.Comment: to appear in proceedings of the NATO Advanced Research Worksho

Chiral drag force

We provide a holographic evaluation of novel contributions to the drag force acting on a heavy quark moving through strongly interacting plasma. The new contributions are chiral in that they act in opposite directions in plasmas containing an excess of left- or right-handed quarks and in that they are proportional to the coefficient of the axial anomaly. These new contributions to the drag force act either parallel to or antiparallel to an external magnetic field or to the vorticity of the fluid plasma. In all these respects, these contributions to the drag force felt by a heavy quark are analogous to the chiral magnetic effect on light quarks. However, the new contribution to the drag force is independent of the electric charge of the heavy quark and is the same for heavy quarks and antiquarks. We show that although the chiral drag force can be non-vanishing for heavy quarks that are at rest in the local fluid rest frame, it does vanish for heavy quarks that are at rest in a suitably chosen frame. In this frame, the heavy quark at rest sees counterpropagating momentum and charge currents, both proportional to the axial anomaly coefficient, but feels no drag force. This provides strong concrete evidence for the absence of dissipation in chiral transport, something that has been predicted previously via consideration of symmetries. Along the way to our principal results, we provide a general calculation of the corrections to the drag force due to the presence of gradients in the flowing fluid in the presence of a nonzero chemical potential. We close with a consequence of our result that is at least in principle observable in heavy ion collisions, namely an anticorrelation between the direction of the CME current for light quarks in a given event and the direction of the kick given to the momentum of all the heavy quarks and antiquarks in that event.Comment: 28 pages, small improvement to the discussion of gravitational anomaly, references adde

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Gastric atrophy and oesophageal squamous cell carcinoma: Possible interaction with dental health and oral hygiene habit

Background:Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results.Methods:We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs).Results:After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI <55 μg dl-1) was associated with a two-fold increased risk (OR=2.01, 95% CI: 1.18, 3.45) of OSCC in the absence of nonatrophic pangastritis (defined as PGII <11.8 μg dl-1). Stratification by PGII decreased the misclassification errors due to cancer-induced gastritis. Presence of both poor dental health, indicated by higher than median sum of decayed, missing, and filled teeth (DMFT score), and gastric atrophy further increased the risk of OSCC (OR=4.15, 95% CI: 2.04, 8.42) with relative excess risk due to interaction (RERI) of 1.47 (95% CI: 1.15, 4.1). Coexistence of poor oral hygiene habit with gastric atrophy elevated OSCC risk eight times (OR=8.65, 95% CI: 3.65, 20.46) and the additive interaction index was marginally statistically significant (RERI=4.34, 95% CI: 1.07, 9.76).Conclusion:Gastric atrophy is a risk factor for OSCC, and poor dental health and oral hygiene habit may act synergistically in increasing the risk. © 2012 Cancer Research UK