Why do we not want to recommend influenza vaccination to young children? A qualitative study of Australian parents and primary care providers

Publication date: Available online 5 January 2018
Source:Vaccine
Author(s): Ruby Biezen, Danilla Grando, Danielle Mazza, Bianca Brijnath
IntroductionInfluenza vaccination has been shown to be safe and effective against influenza and in the prevention of complicating secondary respiratory illnesses. However, its uptake in young children remains low. This study explored the views, attitudes and practices of parents and primary care providers (PCPs) on their knowledge and acceptance of influenza vaccination in children under 5.MethodsUsing a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs (i.e., general practitioners, practice nurses, maternal and child health nurses, and pharmacists) and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed.ResultsParents thought the vaccine could cause influenza, and influenza vaccination was not necessary for their children as they needed to build their own 'immunity'. Parents said that they would consider vaccinating their children if recommended by their GP and if the influenza vaccine was part of the immunisation schedule. PCPs also expressed concerns regarding the efficacy of the vaccine as well as out-of-pocket costs incurred by families, and uncertainty regarding the mortality and morbidity of influenza in otherwise healthy children. However, they said they would recommend the vaccine to high-risk groups (e.g. children with chronic disease(s), and asthma).ConclusionDespite the established safety of influenza vaccines, barriers to uptake include concerns regarding the iatrogenic effects of vaccination, its administration schedule, and knowledge of influenza severity. Updated information on influenza and the efficacy of the vaccine, and incorporating influenza vaccination into the immunisation schedule may overcome some of these barriers to increase influenza vaccination in this vulnerable cohort.



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Occurrence of home-based record stock-outs—A quiet problem for national immunization programmes continues

Publication date: Available online 5 January 2018
Source:Vaccine
Author(s): David W. Brown, Marta Gacic-Dobo
Home-based records (HBRs) provide an effective, inexpensive mechanism for recording and tracking infant vaccinations, yet stock-outs prevent HBRs from fulfilling their intended function. We describe the annual occurrence of HBR stock-outs during 2014–2016 reported by national immunization programmes to the WHO and UNICEF on the Joint Reporting Form on Immunization. During 2014–16, 48 countries reported at least one HBR stock-out. Thirteen countries reported HBR stock-outs for two of the three years. Forty-four countries reported two or more HBR funding sources in 2016. Challenges persist in ensuring continuous availability of HBRs. HBR stock-outs have important implications as they may impact continuity-of-care, increase inefficiencies at the point-of-care and reduce the ability of caregivers to be effective health advocates. Identifying mechanisms for preventing stock-outs should be a focus of attention for programmes and development partners. Expanded efforts are required to better understand the underlying causes of HBR stock-outs and identify solutions.



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Effect of Age and Sex on Hospital Readmission in Traumatic Brain Injury

Publication date: Available online 4 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chih-Ying Li, Amol Karmarkar, Deepak Adhikari, Kenneth Ottenbacher, Yong-Fang Kuo
ObjectiveTo investigate the impact of age and sex on 30-, 60- and 90-day hospital readmission after acute hospital discharge for individuals with traumatic brain injury (TBI).DesignRetrospective cohort study.SettingAcute hospitals and post-acute discharge settingsParticipantsFrom the 2013 Nationwide Readmissions Database, we retrieved information on 52,877 individuals with diagnosis-related group codes of TBI. We included only those alive at index acute discharge and excluded those discharged with same-day readmission. We divided our sample into four age groups: 18-40, 41-65, 66-75 and 76+ years old.InterventionsNA.Main Outcome Measure(s)All-cause hospital readmission.ResultsSex differences in 30-, 60- and 90-day hospital readmission were found for all age groups (all p<.05). The largest sex differences in hospital readmission were in the two oldest groups (66-75, 76+). For both sexes, the oldest group (76+) had the highest adjusted 90-day readmission risk [e.g., 90-day readmission: Odds Ratio (OR) = 2.32 (2.01-2.69) for males; OR=1.96 (1.59-2.43) for females]. Among those readmitted within 90 days, the youngest group (18-40 years) had the highest cumulative readmission percent (35% for both sexes) within the first week post-hospital discharge.ConclusionAge and sex were significantly associated with hospital readmission during the first 90 days post-discharge in our TBI sample. Specifically, those aged 66-75 or 76+ had the highest readmission risk over 90 days for both sexes. The findings suggest that clinicians should consider age and sex in discharge planning and for the entire episode of care for the TBI population.



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Neurodynamic techniques versus “sham” therapy in the treatment of carpal tunnel syndrome; a randomized placebo-controlled trial

Publication date: Available online 4 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tomasz Wolny, Paweł Linek
ObjectivesTo evaluate the efficacy of neurodynamic techniques used as the sole therapeutic component compared with "sham" therapy in the treatment of mild and moderatecarpal tunnel syndromes (CTS).DesignSingle blinded, randomized placebo-controlled trial.SettingSeveral medical clinics in the south of Poland.ParticipantsVolunteer sample of 150 patients diagnosed with CTS.Main Outcome MeasuresSymptom severity (SSS) and Functional status (FSS) of Boston Carpal Tunnel Questionnaire (BCTQ).InterventionNeurodynamic techniques were used in the NT (neurodynamic techniques) group, and "sham" therapy was used in the ST ("sham" therapy) group.In neurodynamic techniques, the neurodynamic sequence were used and sliding and tension techniques were used. In "sham"therapy, no neurodynamic sequences were used and therapeutic procedures were performed in an intermediate position. Therapy was conducted twice weekly for a total of 20 therapy sessions.ResultsA baseline assessment revealed no inter-group differences in all examined parameters (p>0.05). After therapy, there was statisticant intra-group improvement in NCS (sensory and motor conduction velocity, motor latency) only for the NT group (p<0.01). After therapy, intra-group statisticant changes also occurred for the NT group in pain assessment, 2PD, SSS and FSS (in all cases p<0.01). There were no group differences in assessment of grip and pinch strength(p>0.05).ConclusionThe use of neurodynamic techniques has a better therapeutic effect compared to "sham" therapy in the treatment of mild and moderate forms of CTS.



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Dose and duration of opioid use in propensity score matched, privately insured opioid users with and without spinal cord injury

Publication date: Available online 4 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brittany N. Hand, James S. Krause, Kit N. Simpson
ObjectiveThe objectives were to: 1) compare the opioid utilization patterns in opioid users with spinal cord injury (SCI) to a propensity score matched general population of opioid users without SCI and 2) identify characteristics of persons with SCI associated with long-term and/or high-dose use of opioids.DesignQuasi-experimental analysis of archival dataSettingData used for the analysis were derived from Thompson Reuters MarketScan® Commercial Claims and Encounters Databases for the years 2012-2013.ParticipantsParticipants (aged 18-64 years) included 1,454 opioid users with SCI and 1,454 propensity score matched opioid users without SCI. The cohorts were matched using demographics including comorbidities, hospital admissions, age, gender, and geographic region.Interventionsn/aMain Outcome MeasuresMedical and pharmacy claims from 2012-2013 MarketScan data were analyzed to characterize whether persons were short term (<90 days) or long-term (≥90 days) opioid users and whether persons had high (≥120 mg) or low (<120 mg) average daily morphine equivalents.ResultsResults indicated persons with SCI were significantly more likely to be long-term users of low-dose short-acting opioids (p<0.0001) and more likely to be on high morphine equivalent doses of long-acting opioids (p<0.0001) than matched controls. Among persons with SCI, those with lumbar/sacral injuries had more days' supply of high-dose long-acting opioids than did persons with thoracic or cervical injuries.ConclusionPersons with SCI are prescribed opioids for longer durations of time and at higher morphine equivalent doses than controls, which may increase risk of opioid dependence or adverse drug events. Findings should be considered in the development of practice guidelines for alternate pain management options or opioid dependence interventions for persons with SCI.



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Alginate as a potential diphase solid dispersion carrier with enhanced drug dissolution and improved storage stability

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Jian Guan, Qiaoyu Liu, Xiaofei Zhang, Yeli Zhang, Rina Chokshi, Haiyang Wu, Shirui Mao
The objective of this study was to explore the feasibility of using alginate as a promising diphase solid dispersion carrier to enhance dissolution rate of BCS II drugs with improved stability. Taking lovastatin and indomethacin as model drugs, solvent evaporation method was used to prepare solid dispersions. The drug/polymer compatibility was predicted by Hansen solubility parameter and the drug/polymer ratio was screened based on dissolution study, drug existing state in solid dispersion was characterized by DSC and XRPD. Accelerated stability of the solid dispersion was assessed and compared with that of HPMCAS based system. Phase behavior of the solid dispersion before and after stability study was characterized using polar microscope and Raman mapping. It was found that the optimal drug/alginate ratio was drug dependent and drug existing state was related to drug/alginate miscibility. Stability studies revealed that alginate improved the stability of solid dispersions regardless of drug existing state and a better stability was obtained compared to HPMCAS based system. Raman mapping and SEM study revealed that micro phase separation of solid dispersion was the main reason for the slight decrease in drug dissolution after accelerating experiment. In conclusion, alginate can be used as a promising diphase solid dispersion carrier with significantly improved dissolution rate and storage stability.

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Melt extrusion process for adjusting drug release of poorly water soluble drug felodipine using different polymer matrices

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Eirini Palazi, Evangelos Karavas, Panagiotis Barmpalexis, Margaritis Kostoglou, Stavroula Nanaki, Evi Christodoulou, Dimitrios N. Bikiaris
The purpose of the present study was to use commercial available polymers like PVP/PEG, soluplus® and kollidon® SR to prepare immediate and sustained release formulations of felodipine by hot melt mixing method. Solid dispersions containing 5, 10, 20 and 30wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130°C and mixing time 10min. As was found from DSC and XDR studies completely amorphous and miscible solid dispersions can be prepared. In all cases a single glass transition was recorded, which is depended from the used drug amount. Hydrogen bonds and the molecular interaction between felodipine and polymer matrices are responsible for the miscibility of prepared formulations. This has as result the substantial enhancement of felodipine release rate in PVP/PEG mixture and due to the high solubility of used polymers immediate release formulations have been prepared. On the contrary, sustained release formulations can be prepared in the case of kollidon SR solid dispersions. The release mechanism of all preparations was studied using different kinetic models. Finally, binding affinity values calculated by molecular docking simulations were used as estimators for predicting long-term drug's physical stability in solid dispersions.

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Mesoporous Silica Nanoparticles Decorated with Polycationic Dendrimers for Infection Treatment

Publication date: Available online 5 January 2018
Source:Acta Biomaterialia
Author(s): Blanca González, Montserrat Colilla, Jaime Díez, Daniel Pedraza, Marta Guembe, Isabel Izquierdo-Barba, María Vallet-Regí
This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named "nanoantibiotics", are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVO-loaded MSNs. After physicochemical characterization of this nanoantibiotic, the release kinetics of LEVO and the antimicrobial efficacy of each released dosage were evaluated. Besides, internalization studies of the MSNs functionalized with the G3 dendrimer were carried out, showing a high penetrability throughout Gram-negative bacterial membranes. This work evidences that the synergistic combination of polycationic dendrimers as bacterial membrane permeabilization agents with LEVO-loaded MSNs triggers an efficient antimicrobial effect on Gram-negative bacterial biofilm. These positive results open up very promising expectations for their potential application in new infection therapies.Statement of significanceSeeking new alternatives to current available treatments of bacterial infections represents a great challenge in nanomedicine. This work reports the design and optimization of a new class of antimicrobial agent, named "nanoantibiotic", based on mesoporous silica nanoparticles (MSNs) decorated with polypropyleneimine dendrimers of third generation (G3) and loaded with levofloxacin (LEVO) antibiotic. The covalently grafting of these G3 dendrimers to MSNs allows an effective internalization in Gram-negative bacteria. Furthermore, the LEVO loaded into the mesoporous cavities is released in a sustained manner at effective antimicrobial dosages. The novelty and originality of this manuscript relies on proving that the synergistic combination of bacteria-targeting and antimicrobial agents into a unique nanosystem provokes a remarkable antimicrobial effect against bacterial biofilm.

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Phase II trial of ipilimumab in melanoma patients with preexisting humoural immune response to NY-ESO-1

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): G.M. Haag, I. Zoernig, J.C. Hassel, N. Halama, J. Dick, N. Lang, L. Podola, J. Funk, C. Ziegelmeier, S. Juenger, M. Bucur, L. Umansky, C.S. Falk, A. Freitag, I. Karapanagiotou-Schenkel, P. Beckhove, A. Enk, D. Jaeger
BackgroundImmune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1–specific immunity.Patients and methodsTwenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks. Primary endpoint was the disease control rate (irCR, irPR or irSD) according to immune-related response criteria (irRC). Secondary endpoints included the disease control rate according to RECIST criteria, progression-free survival and overall survival (OS). Humoural and cellular immune responses against NY-ESO-1 were analysed from blood samples.ResultsDisease control rate according to irRC was 52%, irPR was observed in 36% of patients. Progression-free survival according to irRC was 7.8 months, according to RECIST criteria it was 2.9 months. Median OS was 22.7 months; the corresponding 1-year survival rate was 66.8%. Treatment-related grade 3 AEs occurred in 36% with no grade 4–5 AEs. No clear association was found between the presence of NY-ESO-1–specific cellular or humoural immune responses and clinical activity.ConclusionIpilimumab demonstrated clinically relevant activity within this biomarker-defined population. NY-ESO-1 positivity, as a surrogate for a preexisting immune response against tumour antigens, might help identifying patients with a superior outcome from immune checkpoint blockade.Clinical trial information: NCT01216696



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Ethnopharmacological uses, phytochemistry and pharmacology of genus Adiantum: A comprehensive review

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Subha Rastogi, Madan Mohan Pandey, Ajay Kumar Singh Rawat
Ethnopharmacological relevanceGenus Adiantum (Pteridaceae) forms a significant dominant component of many plant communities especially in the tropical and temperate regions. These are commonly known as maidenhair ferns and several have been used medicinally in different parts of the world. They exhibit antidysenteric, antiulcer, antimicrobial, antitumor and antiviral activities. The traditional uses of Adiantum species are known to be for respiratory problems such as cough cold, fever, pneumonia and mucous formation.Aim of the reviewThis review aims to provide a comprehensive and updated, categorized information on the botanical aspects, traditional uses, phytochemistry, pharmacological activities and toxicological research of Adiantum species in order to explore their therapeutic potential and evaluate future research opportunities.Materials and methodsThe available information on various species belonging to the genus Adiantum was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals.ResultsThe literature provided information on several ethnopharmacologically well known Adiantum species, the best studied species being A. capillus-veneris. From these plant species, more than 130 compounds belonging to triterpenoids, flavanoids, phenyl propanoids, phenolics, coumarins, phytosterols, fatty acids and others were identified. Experimental evidences confirmed that the Adiantum species could be used in treating microbial infections, diabetes, liver disorders as well as inflammatory disorders.ConclusionsPlants belonging to the genus Adiantum have offered bioactive crude extracts as well as pure compounds, thus substantiating their effectiveness in traditional medicine. Although toxicity studies carried out on some Adiantum species have showed them to be non-toxic, further toxicological studies are still required to confirm their safety in humans. Future research should be directed towards implementing an integrated approach through intensive investigations of all the species of Adiantum relating to phytochemical and pharmacological properties, especially bio-assay guided isolation of phytoconstituents, their mechanism of action, as well as their bioavailability and pharmacokinetics, safety and efficacy.

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Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Ritesh Kumar, Renu Arora, Amit Agarwal, Y.K. Gupta
Ethnopharmacological relevanceTeminalia chebula (TC) has been traditionally used in the Ayurvedic system of medicine primarily for gastrointestinal disorders. Its fruit extract has also been used to treat epilepsy and other CNS disorders.Aim of the studyTo evaluate the effect of hydroalcoholic fruit extract of Terminalia chebula (HETC) on experimental models of seizures, seizure-induced cognitive impairment and oxidative stress in rats.Materials and methodsIn vitro antioxidant activity of HETC was evaluated by using ABTS, NO and DPPH radical scavenging assay. For in-vivo study, seizures were induced in Wistar rats (200–225g) by pentylenetetrazole (PTZ) and maximal-electroshock. (MES). The anticonvulsant effect of the HETC (250, 500, and 1000mg/kg, orally) was evaluated in seizure models. The therapeutic and sub-therapeutic dose of valproate and phenytoin were also assayed. The potential effect of co-administration of HETC (500mg/kg) with sub-therapeutic dose of valproate and phenytoin were also evaluated in PTZ and MES seizures model respectively. Effect on cognition was assessed using elevated plus maze (EPM) and passive avoidance test (PA). The in- vivo oxidative stress parameters (malondialdehyde and glutathione) were assessed in the cerebral cortex and hippocampus part of rat brain.ResultsThe IC50 value of HETC in in vitro antioxidant assays i.e. ABTS, DPPH and NO radical scavenging assay was found to be 2.27μg/ml, 6.04μg/ml and 4.37μg/ml respectively. In experimental study, PTZ and MES treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in EPM and PA as compared to PTZ and MES treated group.ConclusionsThe findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

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In vitro and in vivo evaluation of systemic and genetic toxicity of Citrus unshiu peel

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Hwayong Park, Youn-Hwan Hwang, Jang-Gi Choi, Jin Yeul Ma
Ethnopharmacological relevanceThe peel of Citrus unshiu Markovich fruits (CUP), called "Jinpi" in Korea, and "Chenpi" in China, has been used for the treatment of respiratory and blood circulation disorders in traditional oriental medicine (TOM). Despite its widespread uses in TOM, no information on the safety of CUP has been reported. Thus, genotoxicity and systemic toxicity of CUP were evaluated in the current studies.Materials and methodsWe conducted a toxicological evaluation of CUP water extracts using acute and subchronic (13-week repeated-dose) toxicity tests and three genotoxicity assays (bacterial reverse mutation, mammalian chromosomal aberration, and micronuclei formation).ResultsIn acute and subchronic toxicity tests, both the median lethal dose (LD50) and no-observed-adverse-effect level (NOAEL) were more than 4000mg/kg/day in rats. None of the genotoxicity assays revealed any mutagenicity or clastogenicity in in vitro and in vivo systems.ConclusionCUP water extracts were found to be nongenotoxic under our testing conditions and had low acute and subchronic toxicity.

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Antidepressant-like effects of water extract of Gastrodia elata Blume on neurotrophic regulation in a chronic social defeat stress model

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Yu-En Lin, Shao-Ting Chou, Shih-Hang Lin, Kuan-Hung Lu, Suraphan Panyod, Yi-Syuan Lai, Chi-Tang Ho, Lee-Yan Sheen
Ethnopharmacology relevanceGastrodia elata Blume (GE) is a traditional Chinese medicine commonly used to treat dizziness, epilepsy, paralysis and some emotional symptoms in east Asia. We previously showed that the water extract of Gastrodia elata Blume (WGE) possesses anti-depression like effects in a forced swimming test and chronic mild stress model.Aim of the studyThe aim of this study was to investigate the antidepressant-like effects of WGE and potential mechanisms related to brain-derived neurotrophic factor (BDNF) regulation in mice exposed to chronic social defeat stress (CSDS) model.Materials and methodsFifty C57BL/6 mice were divided into 5 groups as follows: a control (CTL) group, CSDS group, and 3 WGE groups receiving 250, 500 or 1000mg/kg body weight in the CSDS model. Mice were administered WGE for 24 days by oral gavage, and the social defeat stress paradigm began on day 14, except for the control group. A social interaction test was conducted to evaluate the antidepressant-like effects of WGE. Blood samples were collected to measure serum corticosterone levels, and the brain was dissected to investigate the expression of BDNF-related signaling pathway proteins using western blotting.ResultsOral administration of WGE improved depression-like behaviors and stress-induced elevations of corticosterone. Further, WGE increased the protein expression of BDNF and promoted the hippocampal protein phosphorylation ratio of cAMP response element binding protein (CREB) and protein kinase B (Akt).ConclusionWGE exerts antidepressant-like effects on mice in a CSDS model, likely through activating of the BDNF/CREB/Akt pathway. Therefore, WGE has potential as a supplement or an adjuvant to prevent or treat clinical depressive disorders.

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Antioxidant and anti-glycation capacities of some medicinal plants and their potential inhibitory against digestive enzymes related to type 2 diabetes mellitus

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Rodrigo Rodrigues Franco, Danúbia da Silva Carvalho, Francyelle Borges Rosa de Moura, Allisson Benatti Justino, Heitor Cappato Guerra Silva, Leonardo Gomes Peixoto, Foued Salmen Espindola

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Multiple perspectives of qingkailing injection-fraction-single compound in revealing the hepatotoxicity of baicalin and hyodeoxycholic acid

Publication date: 6 April 2018
Source:Journal of Ethnopharmacology, Volume 215
Author(s): Jiayu Zhang, Shifeng Wang, Lulu Xu, Qiao Zhang, Zhanpeng Shang, Yanling Zhang, Qinghua Wu, Shiyou Li, Yanjiang Qiao
Ethnopharmacological relevanceThe complexity of ingredients in traditional Chinese medical formulas and the limited consideration of toxicological responses are fundamental issues that hamper prognostic information of drug quality control.Materials and methodsA multidisciplinary approach for quality control of Qingkailing injection (QKL) regarding drug induced liver toxicity was described for the first time. High content image analysis (HCA) was combined with reverse-phase chromatographic separation and high-resolution MS detection technologies to provide the dynamic responses of drug induced HepG2 cell injury. Firstly, a simple and rapid method for simultaneous qualification and quantification of 21 major constituents in QKL was established and validated using ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometer (UHPLC-Q-Orbitrap), which were operated in full MS/dd-MS² mode and thus simultaneously acquired quantitative high resolution (HR) full scan data and confirmatory HR MS² data. Secondly, repeated semi-preparation HPLC was applied to obtain four fractions (F1-F4) for HCS analysis. Finally, potential hepatotoxicity was determined by five hepatotoxicity biomarkers, including cell loss, DNA condense, glutathione (GSH) depletion, reactive oxygen species (ROS) formation, and mitochondria membrane potential (MMP) depolarization.ResultsThe detection in polarity switching mode empowered the coverage of comprehensive constituents with different chemical properties. Satisfactory linearity precisions, repeatability, stability, and recovery were achieved. QKL injection significantly induced HepG2 cell injury above the concentration of 1.25% (v/v). Meanwhile, flavone glycosides (F3) and stinasterols (F4) fractions exhibited hepatotoxicity above 75μg/mL and 50μg/mL, respectively. Still further, baicalin originated from F3 significantly caused cell loss and glutathione (GSH) depletion. In parallel, hyodeoxycholic acid from F4 induced cell loss, nucleus condense, and GSH reduction as well.ConclusionsOur work provides multiple perspectives based on injection-fractions-single compound format to improve QKL pharmacovigilance through revealing the potential hepatotoxic material basis. Additionally, our study provides an integrating paradigm for the comprehensive and systematic quality control of traditional Chinese medical formulas.

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Action of the hydroethanolic extract of the flowers of Acmella oleracea (L.) R.K. Jansen on the reproductive performance of Wistar females rats: A popular female aphrodisiac from the Amazon

Publication date: 25 March 2018
Source:Journal of Ethnopharmacology, Volume 214
Author(s): Clarice Flexa da Rocha, Yuri de Medeiros Souza Lima, Helison Oliveira Carvalho, Rodrigo Costa Pinto, Irlon Maciel Ferreira, Andres Navarrete Castro, Clarissa Silva Lima, José Carlos Tavares Carvalho
Ethnopharmacological relevanceThe species Acmella oleracea (L.) R.K. Jansen (Asteraceae), popularly known as jambú, is marketed in fairs as a female aphrodisiac and has several pharmacological activities already confirmed, among them the sexual stimulant action. The objective of this study was to evaluate the effects of the oral administration of the hydroethanolic extract of A. oleracea flowers (EHAo) on wistar rats during the pre-mating, mating, and pre-implantation period.Material and methodsDuring the treatment period, measurements of feed intake, water intake, weight, estrous cycle, behavior, reproductive parameters, biochemical parameters, hematological parameters, and histopathology of ovaries were performed daily.ResultsIn the gas chromatography analysis - mass spectrometry characterization, the compound (2E, 6Z, 8E) -N-isobutyldeca-2,6,8-trienamide (spilanthol) was detected as the majority compound at the 84% concentration. In the conditions of this study, EHAo did not cause maternal toxicity. However, in the estrous cycle, the frequency of the Proestrous (P) and Estrous (E) phase was significantly increased with the doses of 88.91 and 444.57mg/kg of the EHAo in relation to the control. On the other hand, the metaestrous (M) and diestrous (D) phases showed a significant reduction in their frequency in the groups treated with EHAo. Water intake increased significantly (p < 0.01), as well as the triglyceride levels, the total cholesterol and fractions (p < 0.05), and the percentage of neutrophils (p < 0.05).ConclusionIt is concluded, therefore, that the treatment with EHAo, which is one of the forms popularly used, is safe in the concentrations and time of treatment studied as it is able to influence the estrous cycle without altering folliculogenesis and fertility.

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Air bio-battery with a gas/liquid porous diaphragm cell for medical and health care devices

Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103
Author(s): Takahiro Arakawa, Rui Xie, Fumiya Seshima, Koji Toma, Kohji Mitsubayashi
Powering future generations of medical and health care devices mandates the transcutaneous transfer of energy or harvesting energy from the human body fluid. Glucose-driven bio fuel cells (bio-batteries) demonstrate promise as they produce electrical energy from glucose, which is a substrate presents in physiological fluids. Enzymatic biofuel cells can convert chemical energy into electrical energy using enzymes as catalysts. In this study, an air bio-battery was developed for healthcare and medical applications, consisting of a glucose-driven enzymatic biofuel cell using a direct gas-permeable membrane or a gas/liquid porous diaphragm. The power generation characteristics included a maximum current density of 285μA/cm² and maximum power density of 70.7μW/cm² in the presence of 5mmol/L of glucose in solution. In addition, high-performance, long-term-stabilized power generation was achieved using the gas/liquid porous diaphragm for the reactions between oxygen and enzyme. This system can be powered using 5mmol/L of glucose, the value of which is similar to that of the blood sugar range in humans.



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Microfluidic platform for single cell analysis under dynamic spatial and temporal stimulation

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Jiyoung Song, Hyunryul Ryu, Minhwan Chung, Youngtaek Kim, Yannick Blum, Sung sik Lee, Olivier Pertz, Noo Li Jeon
Recent research on cellular responses is shifting from static observations recorded under static stimuli to real-time monitoring in a dynamic environment. Since cells sense and interact with their surrounding microenvironment, an experimental platform where dynamically changing cellular microenvironments should be recreated in vitro. There has been a lack of microfluidic devices to support spatial and temporal stimulations in a simple and robust manner. Here, we describe a microfluidic device that generates dynamic chemical gradients and pulses in both space and time using a single device. This microfluidic device provides at least 12h of continuous stimulations that can be used to observe responses from mammalian cells. Combination of the microfluidic de­vice with live-cell imaging facilitates real-time observation of dynamic cellular response at single cell level. Using stable HEK cells with biosensors, ERK (Extracellular signal-Regulated Kinase) activities were observed un­der the pulsatile and ramping stimulations of EGF (Epidermal Growth Factor). We quantified ERK activation even at extremely low EGF concentration (0.0625µg/ml), which can not be observed using conventional techniques such as western blot. Cytoskeleton re­arrangement of the 3T3 fibroblast (stable transfection with Lifeact-GFP) was compared under abrupt and gradually changing gradient of PDGF.



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Editorial Board

Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103





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Minimizing the effects of oxygen interference on l-lactate sensors by a single amino acid mutation in Aerococcus viridans l-lactate oxidase

Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103
Author(s): Kentaro Hiraka, Katsuhiro Kojima, Chi-En Lin, Wakako Tsugawa, Ryutaro Asano, Jeffrey T. La Belle, Koji Sode
l-lactate biosensors employing l-lactate oxidase (LOx) have been developed mainly to measure l-lactate concentration for clinical diagnostics, sports medicine, and the food industry. Some l-lactate biosensors employ artificial electron mediators, but these can negatively impact the detection of l-lactate by competing with the primary electron acceptor: molecular oxygen. In this paper, a strategic approach to engineering an AvLOx that minimizes the effects of oxygen interference on sensor strips was reported. First, we predicted an oxygen access pathway in Aerococcus viridans LOx (AvLOx) based on its crystal structure. This was subsequently blocked by a bulky amino acid substitution. The resulting Ala96Leu mutant showed a drastic reduction in oxidase activity using molecular oxygen as the electron acceptor and a small increase in dehydrogenase activity employing an artificial electron acceptor. Secondly, the Ala96Leu mutant was immobilized on a screen-printed carbon electrode using glutaraldehyde cross-linking method. Amperometric analysis was performed with potassium ferricyanide as an electron mediator under argon or atmospheric conditions. Under argon condition, the response current increased linearly from 0.05 to 0.5mM l-lactate for both wild-type and Ala96Leu. However, under atmospheric conditions, the response of wild-type AvLOx electrode was suppressed by 9–12% due to oxygen interference. The Ala96Leu mutant maintained 56–69% of the response current at the same l-lactate level and minimized the relative bias error to −19% from −49% of wild-type. This study provided significant insight into the enzymatic reaction mechanism of AvLOx and presented a novel approach to minimize oxygen interference in sensor applications, which will enable accurate detection of l-lactate concentrations.



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