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.

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.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Targeted disruption of the JAK2/STAT3 pathway in combination with systemic administration of paclitaxel inhibits the priming of ovarian cancer stem cells leading to a reduced tumor burden

Chemotherapy resistance associated with recurrent disease is the major cause of poor survival of ovarian cancer patients. We have recently demonstrated activation of the JAK2/STAT3 pathway and the enhancement of a cancer stem cell (CSC)-like phenotype in ovarian cancer cells treated in vitro with chemotherapeutic agents. To elucidate further these mechanisms in vivo,we used a two-tiered paclitaxel treatment approach in nude mice inoculated with ovarian cancer cells. In the first approach, we demonstrate that a single intraperitoneal administration of paclitaxel in mice 7 days after subcutaneous transplantation of the HEY ovarian cancer cell line resulted in a significant increase in the expression of CA125, Oct4, and CD117 in mice xenografts compared to control mice xenografts which did not receive paclitaxel. In the second approach, mice were administered once weekly with paclitaxel and/or a daily dose of the JAK2-specific inhibitor, CYT387, over 4weeks. Mice receiving paclitaxel only demonstrated a significant decrease in tumor volume compared to control mice. At the molecular level, mouse tumors remaining after paclitaxel administration showed a significant increase in the expression of Oct4 and CD117 coinciding with a significant activation of the JAK2/STAT3 pathway compared to control tumors. The addition of CYT387 with paclitaxel resulted in the suppression of JAK2/STAT3 activation and abrogation of Oct4 and CD117 expression in mouse xenografts. This coincided with significantly smaller tumors in mice administered CYT387 in addition to paclitaxel, compared to the control group and the group of mice receiving paclitaxel only. These data suggest that the systemic administration of paclitaxel enhances Oct4- and CD117-associated CSC-like marker expression in surviving cancer cells in vivo, which can be suppressed by the addition of the JAK2-specific inhibitor CYT387, leading to a significantly smaller tumor burden. These novel findings have the potential for the development of CSC-targeted therapy to improve the treatment outcomes of ovarian cancer patients.

Doctors' knowledge of the law on withholding and withdrawing life-sustaining medical treatment

Objectives To examine the level of knowledge of doctors about the law on withholding and withdrawing life-sustaining treatment from adults who lack decision-making capacity, and factors associated with a higher level of knowledge. Design, setting and participants Postal survey of all specialists in emergency medicine, geriatric medicine, intensive care, medical oncology, palliative medicine, renal medicine and respiratory medicine on the AMPCo Direct database in New South Wales, Victoria and Queensland. Survey initially posted to participants on 18 July 2012 and closed on 31 January 2013. Main outcome measures Medical specialists’ levels of knowledge about the law, based on their responses to two survey questions. Results Overall response rate was 32%. For the seven statements contained in the two questions about the law, the mean knowledge score was 3.26 out of 7. State and specialty were the strongest predictors of legal knowledge. Conclusions Among doctors who practise in the end-of-life field, there are some significant knowledge gaps about the law on withholding and withdrawing life-sustaining treatment from adults who lack decision-making capacity. Significant consequences for both patients and doctors can flow from a failure to comply with the law. Steps should be taken to improve doctors’ legal knowledge in this area and to harmonise the law across Australia.

‘Hiring a Nashville sensation’ : using narrative learning to develop the problem solving skills of contract law students

This article discusses the design of interactive online activities that introduce problem solving skills to first year law students. They are structured around the narrative framework of ‘Ruby’s Music Festival’ where a young business entrepreneur encounters various issues when organising a music festival and students use a generic problem solving method to provide legal solutions. These online activities offer students the opportunity to obtain early formative feedback on their legal problem solving abilities prior to undertaking a later summative assessment task. The design of the activities around the Ruby narrative framework and the benefits of providing students with early formative feedback will be discussed.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Inappropriate formulation choices in the administration of medication to elderly patients with dysphagia in nursing homes

Inappropriate food or medication texture in patients with dysphagia is the most significant risk factor for pneumonia. Dysphagia is prevalent within care homes for the older person as it is largely found in conditions associated with ageing. This study was designed to determine the appropriateness of medication formulation choices in elderly patients with dysphagia in care homes.

The Pirate Bazaar: The Social Life of Copyright Law

This thesis provides a cultural history of Australian copyright law and related artistic controversies. It examines a number of disputes over authorship, collaboration, and appropriation across a variety of cultural fields. It considers legal controversies over the plagiarism of texts, the defacing of paintings, the sampling of musical works, the ownership of plays, the co-operation between film-makers, the sharing of MP3 files on the Internet, and the appropriation of Indigenous culture. Such narratives and stories relate to a broad range of works and subject matter that are protected by copyright law. This study offers an archive of oral histories and narratives of artistic creators about copyright law. It is founded upon interviews with creative artists and activists who have been involved in copyright litigation and policy disputes. This dialogical research provides an insight into the material and social effects of copyright law. This thesis concludes that copyright law is not just a ‘creature of statute’, but it is also a social and imaginative construct. In the lived experience of the law, questions of aesthetics and ethics are extremely important. Industry agreements are quite influential. Contracts play an important part in the operation of copyright law. The media profile of personalities involved in litigation and policy debates is pertinent. This thesis claims that copyright law can be explained by a mix of social factors such as ethical standards, legal regulations, market forces, and computer code. It can also be understood in terms of the personal stories and narratives that people tell about litigation and copyright law reform. Table of Contents Prologue 1 Introduction A Creature of Statute: Copyright Law and Legal Formalism 6 Chapter One The Demidenko Affair: Copyright Law and Literary Works 33 Chapter Two Daubism: Copyright Law and Artistic Works 67 Chapter Three The ABCs of Anarchism: Copyright Law and Musical Works 105 Chapter Four Heretic: Copyright Law and Dramatic Works 146 Chapter Five Shine: Copyright Law and Film 186 Chapter Six Napster: Infinite Digital Jukebox or Pirate Bazaar? Copyright Law and Digital Works 232 Chapter Seven Bangarra Dance Theatre: Copyright Law and Indigenous Culture 275 Chapter Eight The Cathedral and the Bazaar: The Future of Copyright Law 319

Estate contestation in Australia: An empirical study of a year of case law

This article reports on a study which reviewed all publicly available succession law judgments in Australia during a 12-month period. The article begins with a brief overview of the relevant Australian law and the method adopted for the case review to provide some context for the analysis that follows. It then shifts to its primary objective: to provide an overview of Australian estate litigation during this period with a particular focus on analysing the family provision contests, which comprised over half the cases in the sample. The article examines how many estates were subject to family provision claims, who were contesting them, and to what extent those challenges were successful. The article also considers variation in estate litigation across Australian states and the impact of estate size on contests. It concludes by identifying the themes that emerged from these judicial cases and outlines their significance for law and practice reform.

Effect Of Administration Of Luteinizing-Hormone (Lh) And Deprivation Of Lh On The Proteins Of Smooth Endoplasmic-Reticulum Of Immature And Adult-Rat Leydig-Cells

Analysis of proteins of smooth endoplasmic reticulum (SER) of Leydig cells from immature and admit rats by two-dimensional polyacrylamide gel electrophoresis (SDS-PAGE) revealed the presence of several new proteins in the adult rats. Administration of human chorionic gonadotropin to immature rats for ten days also resulted in a significant increase as well as the appearance of several new proteins. The general pattern of SDS-PAGE analysis of the SER proteins of Leydig cells resembled that of the adult rat. SDS-PAGE analysis of the SER proteins of Leydig cells from adult rats following deprivation of endogenous luteinizing hormone by administration of antiserum to ovine luteinizing hormone resulted in a pattern which to certain extent resembled that of an immature I at. Western Blot analysis of luteinizing hormone antiserum treated rat Leydig cell proteins revealed a decrease in the 17-alpha-hydroxylase compared to the control. These results provide biochemical evidence for the suggestion that one of the main functions of luteinizing hormone is the control of biogenesis and/or turnover SER of Leydig cells in the rat.

The Role of the Law in Communicating Patient Safety

This chapter considers the role of the law in communicating patient safety. Downie, Lahey, Ford, et al’s (2006) preventing, knowing and responding theoretical framework is adopted to classify the different elements of patient safety law. Rather than setting out all relevant patient safety laws in detail, this chapter highlights key legal strategies which are employed to: prevent the occurrence of patient safety incidents (preventing); support the discovery and open discussion of patient safety incidents when they do occur (knowing),; and guide responses after they occur (responding) (Downie, Lahey, Ford, et al 2006). The law is increasingly being invoked to facilitate open discussion of and communication surrounding patient safety. After highlighting some legal strategies used to communicate patient safety, two practice examples are presented. The practice examples highlight different aspects of patient safety law and are indicative of communication issues commonly faced in practice. The first practice example focuses on the role of the Ccoroner in communicating patient safety. This example highlights the investigative role of the law in relation to patient safety (knowing). It also showcases the preventing responding and preventing elements in respect of the significant number of communication errors that can occur in a multi-disciplinary, networked health system. The main focus of the second practice example is responding example illustrates how the law responds to health service providers’ and professionals’ miscommunication (and subsequent incidents) during treatment, however it also touches upon knowing and preventing.

Functional changes in rat liver mitochondria on administration of 2-methyl-4-dimethylaminoazobenzene

Administration of 2-methyl-4-dimethylaminobenzene in the diet (0.1%, w/w) for 85-90 days doubled the content of mitochondria in the livers of rats. The azodye was covalently bound to liver proteins, and about 15% of the amount found in liver was associated with the mitochondrial fraction. Mitochondria isolated from the livers of azodye-fed animals showed drastically lowered ability to oxidize NAD+-linked substrates. The inhibited electron-transfer step was the reduction of ubiquinone. The organelles showed a large increase in succinate oxidase activity. The activity of cytochrome oxidase and the content of cytochrome aa3 were substantially higher in these organelles. Azodye-fed animals showed depressed serum cholesterol concentrations. The content of ubiquinone in liver also registered a small increase.

Effect of administration of clofibrate and clofenapate on kidney mitochondria of the rat

Abstract is not available.