bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterising the behaviour of poorly water soluble drugs in the intestine: application of biorelevant media for solubility, dissolution and transport studies
Authors: Kleberg Karen , Jacobsen Jette , Müllertz Anette 
Published: July 2010

AbstractObjectivesBased on the knowledge of human intestinal fluids, compositions of biorelevant media and their impact on solubility, dissolution and permeability studies of poorly soluble drug compounds are discussed.Key findingsHuman intestinal fluids show large variations with regard to composition and pH, which complicate the selection of biorelevant media. The influence of concentration and ratio of bile salts, phospholipids and hydrolysis products, such as monoglycerides and free fatty acids, in well characterised media, on the solubility, dissolution and permeability of a given drug provides valuable information on the behaviour of the drug in the intestine, thus enabling the prediction of the in-vivo absorption.SummaryThis review discusses the implications of biorelevant media composition on the solubility, dissolution and permeability of poorly soluble drug compounds. Biorelevant media contain bile salts and phospholipids and when simulating the fed state also monoglycerides and free fatty acids. Solubility of some poorly soluble drugs increase independently of the type of surfactants included in the biorelevant media, while others have a higher solubility in monoglyceride- and fatty acid-containing media. This is independent of the log P (the octanol–water partition coefficient) of the drug. The use of biorelevant dissolution media improves the correlation to in-vivo data, compared with compendial media, and although the field of permeability studies is complex the use of biorelevant media in this setting shows promise with respect to a better prediction of absorption.
Continuing professional pharmacy development needs assessment of Qatar pharmacists
Authors: Wilbur Kerry 
Published: July 2010

Abstract

Objectives
Maintenance and improvement of knowledge, skills and performance for provision of contemporary patient care is at the core of continuing professional pharmacy development (CPPD). Existing CPPD models worldwide reflect different approaches to lifelong learning. Before implementing the first country-wide CPPD programme in Qatar, pharmacists were surveyed to determine their specific continuing education (CE) needs, preferences and attitudes.

Methods
A systematic review of allied-health literature was conducted to help devise an anonymous web-based CPPD needs-assessment survey. Questions were characterized into domains of interest including pharmacist demographics, internet access, frequency and characteristics of past CE activity, preferences for delivery and content, barriers to participation, and plans for future CE activities. All pharmacists in Qatar were invited to participate through e-mail and fax invitations.

Key findings
After 4 months, 134 of 523 (≈25%) pharmacists had completed the survey. Practice sites (hospital and community) and gender were equally represented. Approximately one-third had no or inadequate internet access in the workplace. In the past 2 years, one-quarter had not attended any live local educational programmes. Major obstacles included poor timing (66%) and excessive workload (56%). Most pharmacists preferred interactive CE programme formats and one-third indicated Arabic as delivery language of choice. The majority expressed high motivation to achieve their CPPD goals and only 12% outrightly opposed mandatory CE for pharmacist re-licensure.

Conclusions
Qatar pharmacists demonstrated support for enhanced CE opportunities. While views and preferences mirror those of colleagues elsewhere, current conditions merit careful consideration of CPPD programme development and delivery, including language and technology capabilities.
Is there variability in drug release and physical characteristics of amiodarone chloride from different commercially available tablets? Possible therapeutic implications
Authors: Ngo Suong N T , Barnes Timothy 
Published: July 2010

Abstract

Objectives
Amiodarone is a low-solubility, high-permeability drug with a narrow therapeutic index and reported bioavailability problems associated with switching formulations. The aim of this study was to identify whether there is variability in drug release and physical characteristics of different commercially available amiodarone hydrochloride formulations in Australia.

Methods
Four available formulations (innovator Cordarone (COR) and generic products G1, G2 and G3) were tested for drug dissolution, content uniformity, hardness, weight variation, friability and disintegration in accordance with the US Pharmacopeia specifications.

Key findings
The tested formulations exhibited variable dissolution behaviours: G1 and G3 exhibited the fastest dissolution, G2 dissolution was the slowest and Cordarone showed a medium dissolution. After 3 months' exposure to high temperature (40 ± 2°C) and relative humidity (75 ± 5%), the products exhibited a higher degree of disparity, with drug-release profiles of the generics being markedly different from that of Cordarone. This suggests possible implications on bioequivalence for patients who live in warm/tropical regional areas. Most products met the US Pharmacopeia specifications for drug-content uniformity and other test physical characteristics.

Conclusions
The results suggested that variability in drug release profiles in vitro of amiodarone formulations might be a potential indicator of compromised bioavailability, causing possible interference with the therapeutic response of the drug.
Do researchers use pharmacists' communication as an outcome measure? A scoping review of pharmacist involvement in diabetes care
Authors: Babinec Patricia M , Rock Melanie J , Lorenzetti Diane L , Johnson Jeffrey A 
Published: July 2010

Abstract

Objectives
Pharmacy practice increasingly revolves around obtaining and interpreting information. We investigated whether and how pharmacy practice researchers design their studies in ways that acknowledge verbal communication between pharmacists and patients with diabetes.

Methods
We conducted a scoping review of pharmacists' interventions with patients previously diagnosed as having diabetes with the aim of assessing how many used communication (quality and quantity) as an outcome measure. A scoping review identifies gaps in the literature and draws conclusions regarding the overall state of a research programme, but does not necessarily identify gaps in the quality of the studies reviewed. Quality assessment, therefore, was not conducted. MEDLINE, EMBASE, the Cochrane Library and International Pharmaceutical Abstracts were searched from 2003 to 2008 to identify relevant studies published in English. Reference lists of key studies were also scanned to identify additional studies. Randomized controlled trials and related studies of pharmacists verbal communication with diabetic patients were included.

Key findings
Some 413 abstracts were identified through database and reference searching. Of these, 65 studies met abstract inclusion criteria and 16 studies met full-text inclusion criteria necessary for this review. The majority of included studies report on patients' health outcomes, beliefs about drugs, self-reported health-related quality-of-life scales or some combination of these measures as indicators of pharmacists' interventions. Nine studies included information on the duration of the initial interaction between pharmacists and patients with diabetes; 13 reported on the number of follow-up contacts with pharmacists, and seven studies indicated that pharmacists participating in interventions had received training in diabetes management or in patient-centred care. No studies included or evaluated transcripts of pharmacist–patient interactions.

Summary
Results reveal a gap in the existing literature. In studies of diabetes, pharmacy practice researchers do not appear to consider the influence of pharmacists' communication skills on health outcomes. Future studies should be designed to incorporate a communication research component.
Cross-sectional survey of community pharmacists' views of the electronic Minor Ailment Service in Scotland
Authors: Paudyal Vibhu , Hansford Denise , Scott Cunningham I T , Stewart Derek 
Published: July 2010

Abstract

Objectives
The aim was to investigate community pharmacists' views on the implementation of the electronic Minor Ailment Service (e-MAS) in Scottish community pharmacies and to quantify the barriers and facilitators to service provision.

Methods
A postal cross-sectional survey of all community pharmacies in Scotland (n = 1138) was conducted. A combination of open, closed and Likert-type questions were used.

Key findings
A response rate of 49.5% was achieved. A majority of respondents (over 84%) ranked their level of implementation of e-MAS as 4 or 5 on the five-point scale where point 1 represented ‘not at all’ and 5 represented ‘very high’. A majority also identified opportunities to extend professional roles (83.3%), opportunities for more effective patient treatment (78.5%), opportunities to better meet patient expectations (74.4%) and financial advantage to their pharmacy (52.6%) as benefits of e-MAS. Suspected misuse/overuse of the service by some customers (75.1%) and time required for recording each consultation or supply (61.3%) were two barriers agreed upon by the majority of the respondents.

Conclusions
A majority of respondents had positive views towards e-MAS. The benefits agreed upon by the majority of the respondents relate to known facilitators of community pharmacy practice change. Major barriers, namely suspected misuse of the service by some customers and timely process for recording consultation or supply, could affect pharmacists' efficiency in service delivery and need to be addressed. These results could inform similar schemes that may be introduced locally in the UK or elsewhere.
In Vitro
Sensitivity of
Plasmodium falciparum
Clinical Isolates from the China-Myanmar Border Area to Quinine and Association with Polymorphism in the Na
+
/H
+
Exchanger
Authors: Meng Hao , Zhang Rongping , Yang Henglin , Fan Qi , Su Xinzhuan , Miao Jun , Cui Liwang , Yang Zhaoqing 
Published: July 2010

ABSTRACT

Quinine resistance (QNR) in
Plasmodium falciparum
has been detected in many regions of the world where malaria is endemic. Genetic polymorphisms in at least four genes are implicated in QN susceptibility, and their significance often depends on the genetic background of the parasites. In this study, we have culture-adapted 60
P. falciparum
clinical isolates from the China-Myanmar border and assessed their
in vitro
responses to QN. Our results showed that >50% of the parasite isolates displayed reduced sensitivity to QN, with a half-maximal inhibitory concentration (IC
50
) above 500 nM. Genotyping of
pfcrt
found that an overwhelming proportion of the parasite population had the chloroquine-resistant genotype, whereas
pfmdr1
mutation genotypes and gene amplification were rare. Genotyping of the
P. falciparum
Na
+
/H
+
exchanger gene (
pfnhe1
) at the minisatellite ms4760 locus identified 10 haplotypes. Haplotype 7, which harbors three copies of the DNNND repeat, was the most predominant, accounting for nearly half of the parasite isolates. Correlation studies did not reveal significant associations of the polymorphisms in
pfcrt
and
pfmdr1
genes with QN response. However, the ms4760 haplotypes were highly associated with
in vitro
QN responses. In particular, parasite isolates with an increased DNNND copy number tended to have significantly reduced QN susceptibility, whereas parasite isolates with a higher NHNDNHNNDDD copy number had increased QN susceptibility. This study provided further support for the importance of
pfnhe1
polymorphisms in influencing QNR in
P. falciparum
.
Activity of a Trisubstituted Pyrrole in Inhibiting Sporozoite Invasion and Blocking Malaria Infection
Authors: Panchal Dhruv , Bhanot Purnima 
Published: July 2010

ABSTRACT

Malaria infection is initiated by
Plasmodium
sporozoites infecting the liver. Preventing sporozoite infection would block the obligatory first step of the infection and perhaps reduce disease severity. In addition, such an approach would decrease
P
lasmodium
vivax
hypnozoite formation and therefore disease relapses. Here we describe the activity of a trisubstituted pyrrole, 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl] pyridine, in inhibiting motility, invasion, and consequently infection by
P. berghei
sporozoites. In tissue culture, the compound was effective within the first 3 h of sporozoite addition to HepG2 cells.
In vivo
, intraperitoneal administration of the compound significantly inhibited liver-stage parasitemia in
P. yoelii
sporozoite-infected mice and prevented the appearance of blood-stage parasites.
P. berghei
sporozoites lacking the parasite cGMP-dependent protein kinase, the primary target of the compound in erythrocyte-stage parasites, remained infectious to HepG2 cells and sensitive to the drug. These results suggest that the drug has an additional target(s) in sporozoites. We propose that drugs that inhibit sporozoite infection offer a feasible approach to malaria prophylaxis.
IncI1 Plasmid Carrying Extended-Spectrum-β-Lactamase Gene
bla
CTX-M-1
in
Salmonella enterica
Isolates from Poultry and Humans in France, 2003 to 2008
Authors: Cloeckaert Axel , Praud Karine , Lefevre Martine , Doublet Benoît , Pardos Maria , Granier Sophie A. , Brisabois Anne , Weill François-Xavier 
Published: July 2010

ABSTRACT

We report the dissemination of a conjugative IncI1 plasmid carrying
bla
CTX-M-1
, conferring resistance to extended-spectrum cephalosporins, in
Salmonella enterica
isolates from poultry and humans in France from 2003 to 2008. By IncI1 plasmid subtyping, this plasmid was shown to be genetically related to that found in
Escherichia coli
isolates from healthy poultry in France.
The ABC Transporter AnrAB Contributes to the Innate Resistance of
Listeria monocytogenes
to Nisin, Bacitracin, and Various β-Lactam Antibiotics
Authors: Collins Barry , Curtis Nicola , Cotter Paul D. , Hill Colin , Ross R. Paul 
Published: July 2010

ABSTRACT

A
mariner
transposon bank was used to identify loci that contribute to the innate resistance of
Listeria monocytogenes
to the lantibiotic nisin. In addition to highlighting the importance of a number of loci previously associated with nisin resistance (
mprF
,
virRS
, and
telA
), a nisin-sensitive phenotype was associated with the disruption of
anrB
(
lmo2115
), a gene encoding the permease component of an ABC transporter. The contribution of
anrB
to nisin resistance was confirmed by the creation of nonpolar deletion mutants. The loss of this putative multidrug resistance transporter also greatly enhanced sensitivity to bacitracin, gallidermin, and a selection of β-lactam antibiotics. A comparison of the relative antimicrobial sensitivities of a number of mutants established the Δ
anrB
strain as being one of the most bacitracin-sensitive
L. monocytogenes
strains identified to date.
Role for Neutrophils in Host Immune Responses and Genetic Factors That Modulate Resistance toSalmonella entericaSerovar Typhimurium in the Inbred Mouse Strain SPRET/Ei
Authors: Dejager Lien , Pinheiro Iris , Bogaert Pieter , Huys Liesbeth , Libert Claude 
Published: July 2010

ABSTRACTInfection withSalmonella entericaserovar Typhimurium is a complex disease in which the host-bacterium interactions are strongly influenced by genetic factors of the host. We demonstrate that SPRET/Ei, an inbred mouse strain derived fromMus spretus, is resistant toS.Typhimurium infections. The kinetics of bacterial proliferation, as well as histological examinations of tissue sections, suggest that SPRET/Ei mice can control bacterial multiplication and spreading despite significant attenuation of the cytokine response. The resistance of SPRET/Ei mice toS.Typhimurium infection is associated with increased leukocyte counts in the circulation and enhanced neutrophil influx into the peritoneum during the course of infection. A critical role of neutrophils was confirmed by neutrophil depletion: neutropenic SPRET/Ei mice were sensitive to infection withS.Typhimurium and showed much higher bacterial loads. To identify genes that modulate the natural resistance of SPRET/Ei mice toS.Typhimurium infection, we performed a genome-wide study using an interspecific backcross between C3H/HeN and SPRET/Ei mice. The results of this analysis demonstrate that at least two loci, located on chromosomes 6 and 11, affect survival following lethal infection withS.Typhimurium. These two loci contain several interesting candidate genes which may have important implications for the search for genetic factors controllingSalmonellainfections in humans and for our understanding of complex host-pathogen interactions in general.
EspP, a Serine Protease of EnterohemorrhagicEscherichia coli, Impairs Complement Activation by Cleaving Complement Factors C3/C3b and C5
Authors: Orth Dorothea , Ehrlenbach Silvia , Brockmeyer Jens , Khan Abdul Basit , Huber Georg , Karch Helge , Sarg Bettina , Lindner Herbert , Würzner Reinhard 
Published: July 2010

ABSTRACTHemolytic-uremic syndrome (HUS) is a life-threatening disorder characterized by hemolytic anemia, thrombocytopenia, and renal insufficiency. It is caused mainly by infections with enterohemorrhagicEscherichia coli(EHEC). Recently, Shiga toxin 2, the best-studied virulence factor of EHEC, was reported to interact with complement, implying that complement may be involved in the pathogenesis of EHEC-induced HUS. The aim of the present study was to investigate whether or not the serine protease EspP, an important virulence factor of EHEC, interacts with complement proteins. EspP did not have any effect on the integrity of factor H or factor I. However, EspP was shown to cleave purified C3/C3b and C5. Cleavage of the respective complement proteins also occurred in normal human serum (NHS) as a source of C3/C3b or C5 or when purified complement proteins were added to the supernatant of an EspP-producing wild-type strain. Edman degradation allowed unequivocal mapping of all three main C3b fragments but not of the three main C5 fragments. Complement activation was significantly downregulated in all three pathways for C5-depleted serum to which C5, preincubated with EspP, was added (whereas C5 preincubated with an EspP mutant was able to fully reconstitute complement activation). This indicates that EspP markedly destroyed the functional activity, as measured by a commercial total complement enzyme-linked immunosorbent assay (Wieslab). Downregulation of complement by EspPin vivomay influence the colonization of EHEC bacteria in the gut or the disease severity of HUS.
DivIC Stabilizes FtsL against RasP Cleavage
Authors: Wadenpohl Inga , Bramkamp Marc 
Published: July 2010

ABSTRACTThe essential cell division protein FtsL is a substrate of the intramembrane protease RasP. Using heterologous coexpression experiments, we show here that the division protein DivIC stabilizes FtsL against RasP cleavage. Degradation seems to be initiated upon accessibility of a cytosolic substrate recognition motif.
MET Kinase Inhibitor SGX523 Synergizes with Epidermal Growth Factor Receptor Inhibitor Erlotinib in a Hepatocyte Growth Factor–Dependent Fashion to Suppress Carcinoma Growth
Authors: Zhang Yu-Wen , Staal Ben , Essenburg Curt , Su Yanli , Kang Liang , West Rich , Kaufman Dafna , DeKoning Tom , Eagleson Bryn , Buchanan Sean G. , Vande Woude George F. 
Published: July 2010

Abstract
The hepatocyte growth factor (HGF)-MET pathway supports several hallmark cancer traits, and it is frequently activated in a broad spectrum of human cancers (http://www.vai.org/met/). With the development of many cancer drugs targeting this pathway, there is a need for relevant in vivo model systems for preclinical evaluation of drug efficacy. Here, we show that production of the human HGF ligand in transgenic severe combined immunodeficient mice (hHGFtg-SCID mice) enhances the growth of many MET-expressing human carcinoma xenografts, including those derived from lung, breast, kidney, colon, stomach, and pancreas. In this model, the MET-specific small-molecule kinase inhibitor SGX523 partially inhibits the HGF-dependent growth of lung, breast, and pancreatic tumors. However, much greater growth suppression is achieved by combinatorial inhibition with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. Together, these results validate the hHGFtg-SCID mouse model for in vivo determination of MET sensitivity to drug inhibition. Our findings also indicate that simultaneously targeting the MET and EGFR pathways can provide synergistic inhibitory effects for the treatment of cancers in which both pathways are activated. Cancer Res; 70(17); 6880–90. ©2010 AACR.
Distribution and Categorization of Left Ventricular Measurements in the General Population
Authors: Wild Philipp S. , Sinning Christoph R. , Roth Alexander , Wilde Sandra , Schnabel Renate B. , Lubos Edith , Zeller Tanja , Keller Till , Lackner Karl J. , Blettner Maria , Vasan Ramachandran S. , Münzel Thomas , Blankenberg Stefan 
Published: July 2010

Background—
Echocardiography, the dominant imaging modality for quantification of left ventricular metrics, has undergone continuing development in the past few decades. However, given the lack of population-based data, current guidelines are still based on restricted and small data sets analyzed with methods including expert opinion. This work presents empirically derived reference values from a large-scale, epidemiologic study conducted with state-of-the-art imaging technology and methods.

Methods and Results—
The distribution of echocardiographic measurements of the left ventricle was analyzed in a population-based sample of 5000 mid-Europeans from the Gutenberg Heart Study in Germany. The randomly selected, noninstitutionalized sample provides data on apparently healthy individuals, as well as on those with prevalent disease. Standardized echocardiograms were recorded in a comprehensive data set at a single site with centralized training and certification of sonographers. Sex-specific reference limits and categories indicating the grade of deviation from the reference were calculated, and nomograms were created by quantile regression. Detailed information is given on the association between left ventricular geometry and age.

Conclusions—
The rapidly evolving echocardiographic technology with persistent improvements in image quality and new measurement conventions require the evaluation of new reference limits for left ventricular metrics. The present investigation formulates reference limits and nomograms from state-of-the-art technology and methods based on a large population-based data set. The distribution of echocardiographic measures of left ventricular geometry presents, in part, nonlinear associations with age, which should be the subject of future investigations.