Pharmacokinetics of cimifugin in rat plasma after oral administration of the extract of Saposhnikovia divaricatae root : Determination of cimifugin by high performance liquid chromatography coupled with solid phase extraction

High performance liquid chromatography (HPLC) coupled with the solid phase extraction method was developed for determining cimifugin (a coumarin derivative; one of Saposhnikovia divaricatae's constituents) in rat plasma after oral administration of Saposhnikovia divaricatae extract (SDE), and the pharmacokinetics of cimifugin either in SDE or as a single compound was investigated. The HPLC analysis was performed on a commercially available column (4.6 mm x 200 mm, 5 pm) with the isocratic elution of solvent A (Methanol) and solvent B (Water) (A:B=60:40) and the detection wavelength was set at 250 nm. The calibration curve was linear over the range of 0.100-10.040 microg/mL. The limit of detection was 30 ng/mL. At the rat plasma concentrations of 0.402, 4.016, 10.040 microg/mL, the intra-day precision was 6.21%, 3.98%, and 2.23%; the inter-day precision was 7.59%, 4.26%, and 2.09%, respectively. The absolute recovery was 76.58%, 76.61%, and 77.67%, respectively. When the dosage of SDE was equal to the pure compound calculated by the amount of cimifugin, it was found to have two maximum peaks while the pure compound only showed one peak in the plasma concentration-time curve. The pharmacokinetic characteristics of SDE showed the superiority of the extract and the properties of traditional Chinese medicine.

Validating SMPS-measured size distribution of double-mode spherical Silica nanoparticles by Transmission Electron Microscope (TEM)

A nanoparticles size is one of their key physical characteristics that can affect their fate in a human’s respiratory tract (in case of inhalation) and also in the environment. Hence, measuring the size distribution of nanoparticles is absolutely essential and contributes greatly to their characterization. For years, Scanning Mobility Particle Sizers (SMPS), which rely on measuring the electrical mobility diameter of particles, have been used as one of the most reliable real-time instruments for the size distribution measurement of nanoparticles. Despite its benefits, this instrument has some drawbacks, including equivalency problems for non-spherical particles (i.e. assuming a non-spherical particle is equal to a spherical particle of diameter d due to the same electrical mobility), as well as limitations in terms of its use in workplaces, because of its large size and the complexity of its operation...

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Fuel consumption and gas emissions of an automatic transmission vehicle following simple eco-driving instructions on urban roads

Following eco-driving instructions can reduce fuel consumption between 5 to 20% on urban roads with manual cars. The majority of Australian cars have an automatic transmission gear-box. It is therefore of interest to verify whether current eco-driving instructions are e cient for such vehicles. In this pilot study, participants (N=13) drove an instrumented vehicle (Toyota Camry 2007) with an automatic transmission. Fuel consumption of the participants was compared before and after they received simple eco-driving instructions. Participants drove the same vehicle on the same urban route under similar tra c conditions. We found that participants drove at similar speeds during their baseline and eco-friendly drives, and reduced the level of their accelerations and decelerations during eco-driving. Fuel consumption decreased for the complete drive by 7%, but not on the motorway and inclined sections of the study. Gas emissions were estimated with the VT-micro model, and emissions of the studied pollutants (CO2, CO, NOX and HC) were reduced, but no di erence was observed for CO2 on the motorway and inclined sections. The di erence for the complete lap is 3% for CO2. We have found evidence showing that simple eco-driving instructions are e cient in the case of automatic transmission in an urban environment, but towards the lowest values of the spectrum of fuel consumption reduction from the di erent eco-driving studies.

Impact of socio-ecological variability on the transmission of malaria in Yunnan Province, China

This thesis is a population-based epidemiological study to explore the spatial and temporal pattern of malaria, and to assess the relationship between socio-ecological factors and malaria in Yunnan, China. Geospatial and temporal approaches were applied; the high risk areas of the disease were identified; and socio-ecological drivers of malaria were assessed. These findings will provide important evidence for the control and prevention of malaria in China and other countries with a similar situation of endemic malaria.

HPLC method for preliminary analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus

An HPLC with SPE method has been developed for analysis of constituents in rat blood after oral administration of the extract of Acanthopanax senticosus (ASE). The plasma sample was prepared by SPE method equipped with Oasis HLB cartridge (3cc, 60 mg). The analysis was performed on a Dikma Diamonsil RP(18) column (4.6 mmx150 mm, 5 microm) with the gradient elution of solvent A (ACN) and solvent B (0.1% aqueous phosphoric acid, v/v) and the detection wavelength was set at 270 nm. The calibration curve was linear over the range of 0.156-15.625 microg/mL. The LOD was 60 ng/mL. The intraday precision was less than 5.80%, and the interday precision was less than 6.0%. The recovery was (87.30 +/- 1.73)%. As a result, 19 constituents were detected in rat plasma after oral administration of the ASE, including 11 original compounds in ASE and eight metabolites, and three of the metabolites originated from syringin in ASE. Six constituents were identified by comparing with the corresponding reference compounds.

Voltammetric monitoring of gold nanoparticle formation facilitated by glycyl-L-tyrosine : relation to electronic spectra and transmission electron microscopy images

Voltammetric techniques have been introduced to monitor the formation of gold nanoparticles produced via the reaction of the amino acid glycyl-L-tyrosine with Au(III) (bromoaurate) in 0.05 M KOH conditions. The alkaline conditions facilitate amino acid binding to Au(III), inhibit the rate of reduction to Au(0), and provide an excellent supporting electrolyte for voltammetric studies. Data obtained revealed that a range of time-dependent gold solution species are involved in gold nanoparticle formation and that the order in which reagents are mixed is critical to the outcome. Concomitantly with voltammetric measurements, the properties of gold nanoparticles formed are probed by examination of electronic spectra in order to understand how the solution environment present during nanoparticle growth affects the final distribution of the nanoparticles. Images obtained by the ex situ transmission electron microscopy (TEM) technique enable the physical properties of the nanoparticles isolated in the solid state to be assessed. Use of this combination of in situ and ex situ techniques provides a versatile framework for elucidating the details of nanoparticle formation.

A snapshot of 40 years in early childhood education and care through oral histories

The year 2012 marked 40 years since the introduction of the Child Care Act 1972 and the federal government introduced financial support for the provision of child care services in Australia. Significant changes have occurred in social, political and theoretical contexts of early childhood education and care (ECEC) during this time. Bringing these to life, this paper investigates archival data of key changes in ECEC in association with oral histories of staff, parents and children associated with The Gowrie Qld during the years 1972‒2012. With narrative analysis considered alongside historical information, two dominant issues emerge as integral to ECEC in the past, now and the future. These are: 1) what constitutes effective teaching and learning in the educational program and 2) professional expectations in ECEC. Building an historical picture, this paper provides for critical reflection on the past to inform current and future practices.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

Talking the talk : therapeutic jurisprudence and oral competence

In Australian criminal justice systems, a wide range of pathways to sentencing and punishment exist alongside traditional court processes. In particular, therapeutic jurisprudence ('TJ') processes have emerged during the last quarter of a century and now occupy a key position in the criminal justice landscape. This article provides an introduction to TJ, highlighting in particular the emphasis it places on the active participation of offenders, before critically discussing offenders' capacity to engage with TJ processes. The article then summarises the research on the oral competence of offenders, and argues that offenders who lack oral competence may be disadvantaged in TJ processes. Finally, we provide an overview of the limited guidance that has been provided to TJ practitioners on how to maximise the participation of offenders with limited oral competence.

Non-invasive clinical measurement of the viscoelastic properties of tendon using acoustic wave transmission

Background. In isotropic materials, the speed of acoustic wave propagation is governed by the bulk modulus and density. For tendon, which is a structural composite of fluid and collagen, however, there is some anisotropy requiring an adjustment for Poisson's ratio. This paper explores these relationships using data collected, in vivo, on human Achilles tendon and then compares estimates of elastic modulus and hysteresis against published values from in vitro mechanical tests. Methods. Measurements using conventional B-model ultrasound imaging, inverse dynamics and acoustic transmission techniques were used to determine dimensions, loading conditions and longitudinal speed of sound in the Achilles tendon during a series of isometric plantar flexion exercises against body weight. Upper and lower bounds for speed of sound versus tensile stress in the tendon were then modelled and estimates of the elastic modulus and hysteresis of the Achilles tendon derived. Results. Axial speed of sound varied between 1850 and 2090 ms-1 with a non-linear, asymptotic dependency on the level of tensile stress (5-35 MPa) in the tendon. Estimates derived for the elastic modulus of the Achilles tendon ranged between 1-2 GPa. Hysteresis derived from models of the stress-strain relationship, ranged from 3-11%. Discussion. Estimates of elastic modulus agree closely with those previously reported from direct measurements obtained via mechanical tensile tests on major weight bearing tendons in vitro [1,2]. Hysteresis derived from models of the stress-strain relationship is consistent with direct measures from various mamalian tendon (7-10%) but is lower than previous estimates in human tendon (17-26%) [3]. This non-invasive method would appear suitable for monitoring changes in tendon properties during dynamic sporting activities.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Examining the impact of climate change on dengue transmission in the Asia-Pacific region

Dengue fever (DF) is a serious public health concern in many parts of the world. An increase in DF incidence has been observed globally over the past decades. Multiple factors including urbanisation, increased international travels and global climate change are thought to be responsible for increased DF. However, little research has been conducted in the Asia-Pacific region about the impact of these changes on dengue transmission. The overarching aim of this thesis is to explore the spatiotemporal pattern of DF transmission in the Asia-Pacific region and project the future risk of DF attributable to climate change. Annual data of DF outbreaks for sixteen countries in the Asia-Pacific region over the last fifty years were used in this study. The results show that the geographic range of DF in this region increased significantly over the study period. Thailand, Vietnam and Laos were identified as the highest risk areas and there was a southward expansion observed in the transmission pattern of DF which might have originated from Philippines or Thailand. Additionally, the detailed DF data were obtained and the space-time clustering of DF transmission was examined in Bangladesh. Monthly DF data were used for the entire country at the district level during 2000-2009. Dhaka district was identified as the most likely DF cluster in Bangladesh and several districts of the southern part of Bangladesh were identified as secondary clusters in the years 2000-2002. In order to examine the association between meteorological factors and DF transmission and to project the future risk of DF using different climate change scenarios, the climate-DF relationship was examined in Dhaka, Bangladesh. The results show that climate variability (particularly maximum temperature and relative humidity) was positively associated with DF transmission in Dhaka. The effects of climate variability were observed at a lag of four months which might help to potentially control and prevent DF outbreaks through effective vector management and community education. Based on the quantitative assessment of the climate-DF relationship, projected climate change will likely increase mosquito abundance and activity and DF in this area. Assuming a temperature increase of 3.3oC without any adaptation measures and significant changes in socio-economic conditions, the consequence will be devastating, with a projected annual increase of 16,030 cases in Dhaka, Bangladesh by the end of this century. Therefore, public health authorities need to be prepared for likely increase of DF transmission in this region. This study adds to the literature on the recent trends of DF and impacts of climate change on DF transmission. These findings may have significant public health implications for the control and prevention of DF, particularly in the Asia- Pacific region.