Evaluation of herbs as potential alternatives for bear bile and rhino horn used in traditional Chinese medicines: chemical and biological analysis.

There is currently an unsustainable rate of exploitation of certain species of plants and animals for use in traditional medicines. Bear bile and rhino horn are derived from endangered species and are traditionally combined with medicinal herbs as anti-bacterial and anti-inflammatory agents. This study was designed to assess herbs for use as possible alternatives for these two products. Herbs were selected based on their traditional use as antiinflammatory and anti-bacterial agents. Chemical methods were used to confirm the plant species of the herbs and to measure concentrations of metals and pesticide residues as a means for assessing their quality. Antibacterial activities were determined using a direct bioautography technique. Anti-inflammatory activities of the herb extracts and isolated compounds were ascertained using an in vitro nuclear factor kappaB (NF-KB) activity, as assessed by IL-6 luciferase gene reporter assay. A novel assay was developed to estimate drug-herb interactions by measuring the effects of selected herbs and drugs on the production of eicosatrienoic acids from hepatic cytochrome P450 (CYP450) metabolism of arachidonic acid. In addition, CYP3A4 enzyme assays were conducted. The pesticide residue and heavy metal concentrations of the tested herbs was found not to exceed the existing legally permitted concentrations in foodstuffs, but the rhino horn sample contained elevated levels of Cd, Pb, Hg and Zn. Rhino horn was not found to be an effective anti-bacterial or anti-inflammatory agent In the assays used in this study. Seventeen herbs demonstrated anti-bacterial activity. Also, nine herbs demonstrated inhibitory NF-KB activity. Preliminary results indicate that co-administration of Scutel/aria baicalensis, Salvia miltiorrhiza, Rehmann/a glutinosa or Coptidis Rhizoma with drugs metabolised by CYP3A4, could lead to possible drug-herb interactions. Based on the Information obtained in these studies nine herbs are proposed as alternatives to rhino horn; eight herbs and two Kampo medicines are proposed as alternatives to bear bile

Gap bootstrap methods for massive data sets with an application to transportation engineering

In this paper we describe two bootstrap methods for massive data sets. Naive applications of common resampling methodology are often impractical for massive data sets due to computational burden and due to complex patterns of inhomogeneity. In contrast, the proposed methods exploit certain structural properties of a large class of massive data sets to break up the original problem into a set of simpler subproblems, solve each subproblem separately where the data exhibit approximate uniformity and where computational complexity can be reduced to a manageable level, and then combine the results through certain analytical considerations. The validity of the proposed methods is proved and their finite sample properties are studied through a moderately large simulation study. The methodology is illustrated with a real data example from Transportation Engineering, which motivated the development of the proposed methods.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS587 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model

In this study, cell death regulation and induction in AML cell line from a relapsed MLL-rearranged cell model (MOLM-13) was investigated with doxorubin (Dox) and betulinic acid (BetA), singly and in combination. CyQUANT Direct® and Annexin V/propidium iodide double staining were used to measure the cytotoxic and cell death induction effects of the compounds, respectively. Reactive oxygen species (ROS) generation was measured using 2′,7′-dichlorofluorescin diacetate staining. Expressions of proteins and genes were examined by Western blot and reverse transcription polymerase chain reaction analysis, respectively. BetA (20 μM) and Dox (1 μM) indicated a synergistic growth inhibitory effect on MOLM-13 cells. The combined drug caused more cells to reside in irreversible late apoptotic stage compared to the single treatments (p < 0.05). Elevation in ROS may be the synergistic mechanism involved in MOLM-13 cell death since ROS can directly disrupt mitochondrial activity. In contrast, in leukaemic U-937 cells, the combination treatments attenuated Dox-induced cell death. Dox and the drug combination selectively reduced (p < 0.05) a recently reported anti-apoptotic Bcl-2 protein isoform p15-20-Bcl-2 in MOLM-13 by our group, without affecting the usually reported p26-Bcl-2-α. Further studies using known inhibitors of apoptosis are required to confirm the potential of Dox-BetA combination to modulate these pathways

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long‑circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability. The cytotoxic and pro‑apoptotic effects of free BL and liposomal BL were also evaluated. The results demonstrated that 100 nm liposomes were the most stable formulation when compared with 200 and 400 nm liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL (prepared in DMSO), indicating that the liposome may be a potential vehicle to deliver BL for the treatment of CML. Flow cytometry analysis showed that there was significant (P<0.005) cell cycle arrest in the sub‑G1 phase (compared with vehicle control), indicating cell apoptosis following 20 µM liposomal BL or free BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL preparations was further confirmed through the staining of treated cells with Annexin V‑fluorescein isothiocyanate/propidium iodide. A significant increase in reactive oxygen species (ROS) gene­ration was observed in free BL and liposomal BL treated cells, with a higher level of ROS produced from those treated with free BL. This indicated that cell apoptosis induced by BL may be via ROS generation and liposome delivery may further extend the effect through its long‑circulating property

Evidence for the outcomes and impact of clinical pharmacy: context of UK hospital pharmacy practice

Objectives: The role of clinical pharmacists in hospitals has evolved and continues to expand. In the UK, outside of a few national policy drivers, there are no agreed priorities, measures or defined outcomes for hospital clinical pharmacy (CP). This paper aims to (1) highlight the need to identify and prioritise specific CP roles, responsibilities and practices that will bring the greatest benefit to patients and health systems and (2) describe systematic weaknesses in current research methodologies for evaluating CP services and propose a different approach. Method: Published reviews of CP services are discussed using the Economic, Clinical and Humanistic Outcomes framework. Recurring themes regarding study methodologies, measurements and outcomes are used to highlight current weaknesses in studies evaluating CP. Results: Published studies aiming to demonstrate the economic, clinical or humanistic outcomes of CP often suffer from poor research design and inconsistencies in interventions, measurements and outcomes. This has caused difficulties in drawing meaningful conclusions regarding CP’s definitive contribution to patient outcomes. Conclusion: There is a need for more research work in National Health Service (NHS) hospitals, employing a different paradigm to address some of the weaknesses of existing research on CP practice. We propose a mixed-methods approach, including qualitative research designs, and with emphasis on cost-consequence analyses for economic evaluations. This approach will provide more meaningful data to inform policy and demonstrate the contribution of hospital CP activities to patient care and the NHS

Comparative Study of Mathematical Models for Ghana’s Gold Production

Sigmoid functions were used to approximate the cumulative gold production in Ghana. The functions examined were the logistic, Gompertz, Gaussian, Probit and the Hill, which were then used to predict into the future. Although all the five approximated models gave a good estimation of the reality, the Gompertz function was identified to give the best approximation of the observed trend of gold production in Ghana. The model was selected based on its high proportion of variance explained (R2 = 0.9402) as well as having the least value in terms of error (RMSE) and information loss (AIC). The model suggested that gold production could escalate to a level of 7040813 Oz in the future. It also showed that, industrial scale production of gold should be possible even after the year 2050 provided the current upward trend of gold production in Ghana continues. Keywords: Sigmoid, Logistic, Gompertz, Gaussian, Probit, Hill, Gol

Evaluation of herbs as potential alternatives for bear bile and rhino horn used in traditional Chinese medicines : chemical and biological analysis

There is currently an unsustainable rate of exploitation of certain species of plants and animals for use in traditional medicines. Bear bile and rhino horn are derived from endangered species and are traditionally combined with medicinal herbs as anti-bacterial and anti-inflammatory agents. This study was designed to assess herbs for use as possible alternatives for these two products. Herbs were selected based on their traditional use as antiinflammatory and anti-bacterial agents. Chemical methods were used to confirm the plant species of the herbs and to measure concentrations of metals and pesticide residues as a means for assessing their quality. Antibacterial activities were determined using a direct bioautography technique. Anti-inflammatory activities of the herb extracts and isolated compounds were ascertained using an in vitro nuclear factor kappaB (NF-KB) activity, as assessed by IL-6 luciferase gene reporter assay. A novel assay was developed to estimate drug-herb interactions by measuring the effects of selected herbs and drugs on the production of eicosatrienoic acids from hepatic cytochrome P450 (CYP450) metabolism of arachidonic acid. In addition, CYP3A4 enzyme assays were conducted. The pesticide residue and heavy metal concentrations of the tested herbs was found not to exceed the existing legally permitted concentrations in foodstuffs, but the rhino horn sample contained elevated levels of Cd, Pb, Hg and Zn. Rhino horn was not found to be an effective anti-bacterial or anti-inflammatory agent In the assays used in this study. Seventeen herbs demonstrated anti-bacterial activity. Also, nine herbs demonstrated inhibitory NF-KB activity. Preliminary results indicate that co-administration of Scutel/aria baicalensis, Salvia miltiorrhiza, Rehmann/a glutinosa or Coptidis Rhizoma with drugs metabolised by CYP3A4, could lead to possible drug-herb interactions. Based on the Information obtained in these studies nine herbs are proposed as alternatives to rhino horn; eight herbs and two Kampo medicines are proposed as alternatives to bear bile.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Internuclear gene silencing in Phytophthora infestans is established through chromatin remodelling

In the plant pathogen Phytophthora infestans, nuclear integration of inf1 transgenic DNA sequences results in internuclear gene silencing of inf1. Although silencing is regulated at the transcriptional level, it also affects transcription from other nuclei within heterokaryotic cells of the mycelium. Here we report experiments exploring the mechanism of internuclear gene silencing in P. infestans. The DNA methylation inhibitor 5-azacytidine induced reversion of the inf1-silenced state. Also, the histone deacetylase inhibitor trichostatin-A was able to reverse inf1 silencing. inf1-expression levels returned to the silenced state when the inhibitors were removed except in non-transgenic inf1-silenced strains that were generated via internuclear gene silencing, where inf1 expression was restored permanently. Therefore, inf1-transgenic sequences are required to maintain the silenced state. Prolonged culture of non-transgenic inf1-silenced strains resulted in gradual reactivation of inf1 gene expression. Nuclease digestion of inf1-silenced and non-silenced nuclei showed that inf1 sequences in silenced nuclei were less rapidly degraded than non-silenced inf1 sequences. Bisulfite sequencing of the endogenous inf1 locus did not result in detection of any cytosine methylation. Our findings suggest that the inf1-silenced state is based on chromatin remodelling

Evaluation of the effectiveness of Eladi Keram for the treatment of acne vulgaris: a randomised controlled pilot study

Introduction: Acne is a multifactorial and common skin disease which can significantly affect the quality of life of sufferers. In this study, a topical herbal preparation traditionally used in Ayurvedic medicine was evaluated as a treatment for individuals with acne on their shoulders and backs. Methods: Study participants were randomly assigned either to treatment (Eladi Keram) or vehicle control (coconut oil) groups under double blind conditions and instructed on its daily home application. Standardised lesion counting and acne grading were conducted in accordance with US Food and Drug Administration guidelines and with reference to the Leeds Acne Grading Technique. Participants were assessed for severity of the condition at commencement and on day 28 of treatment. Results: The treatment group showed improvements of 42% (p < 0.005) on the Investigators Global Assessment scale, a 60% (p < 0.05) reduction in inflammatory lesions, a 59% (p < 0.05) reduction in non-inflammatory lesions, and a 59% (p < 0.005) reduction in combined lesion count. The control group showed no statistically significant changes for these criteria. Conclusion: This study is the first reported clinical evaluation of Eladi Keram as a treatment for acne and findings suggest that it could be effective in reducing inflammatory and non-inflammatory lesions, warranting further investigation by means of a larger scale clinical trial