bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term stability of quercetin nanocrystals prepared by different methods
Authors: Kakran Mitali , Shegokar Ranjita , Sahoo Nanda Gopal , Gohla Sven , Li Lin , Müller Rainer H 
Published: April 2012

Abstract

Objectives
This study aimed to examine the long-term physical stability of quercetin nanocrystals produced by three methods.

Methods
Quercetin nanocrystals were prepared by high pressure homogenization, bead milling and cavi-precipitation. The nanocrystals produced by these methods were compared for particle size, saturation solubility and dissolution of the drug particles, and were subjected to stability testing.

Key findings
The X-ray diffraction study and microscopic pictures taken under polarized light indicated the crystalline nature of the nanocrystals produced by the three methods. As the crystalline state is relatively more stable than the amorphous state, a good physical stability was expected from the quercetin nanocrystals prepared. The high-pressure homogenized and bead-milled quercetin nanocrystals showed excellent physical stability when stored under refrigeration (4 ± 2°C) and at room temperature (25 ± 2°C) for 180 days. The dissolution properties were not significantly affected on storage at room temperature. However, increase in the storage temperature to 40 ± 2°C led to physical instability. On the other hand, the cavi-precipitated quercetin nanocrystals exhibited a lower stability than the bead-milled and homogenized formulations and did not show the optimum zeta potential values as well. In the case of cavi-precipitated nanocrystals, recrystallization and agglomeration were responsible for the increasing particle size besides the Ostwald ripening phenomenon. The solvents used during cavi-precipitation might have competed with the surfactant for hydration leading to a partial dehydration of the surfactant, which subsequently affected the stability of the quercetin nanocrystals.

Conclusions
High-pressure homogenized and bead-milled quercetin nanocrystals showed better physical stability than the cavi-precipitated ones. Freeze drying immediately after nanocrystal production can help to prevent their agglomeration and thus improve physical stability.
The stopping criteria for mirror‐gazing in body dysmorphic disorder
Authors: Baldock Emma , Anson Martin , Veale David 
Published: April 2012

Objectives. To investigate whether prolonged compulsive mirror‐gazing in body dysmorphic disorder (BDD) is characterized by the prioritization of internally referenced (internal) goals for the mirror session, such as feeling right about one's make‐up or shaven face, over externally referenced (external) goals, such as seeing that one's make‐up is applied, or seeing that there is no more stubble on one's face.Design. Cross‐sectional case control.Methods. Twenty‐one participants with BDD and 18 community controls (CCs) recalled a recent mirror session in a semi‐structured interview and then completed the Mirror‐Gazing Goals and Terminating Factors Questionnaire (MGGTFQ), an instrument developed for the present study.Results. Internal goals were rated as more important in the BDD group than the CC group, but there was no difference between groups in the importance of external goals. The BDD group identified internal goals significantly more frequently than the CC group among their three most important goals. The BDD group reported significantly lower achievement ratings for the three most important goals and were more likely to terminate the session for reasons unrelated to their goals (e.g., frustration). For all participants, the importance of internal goals was positively correlated with the length of the mirror session.Conclusions. The findings support current recommendations for targeting internal goals in interventions for problematic mirror use. Limitations and future directions are discussed, including the need to establish whether the use of internal goals is causally related to the length of the mirror session.Practitioner points
BDD patients prioritize internal goals defined by feeling states when they look in the mirror (e.g., they aim above all to feel right about their make‐up or shaven face), and then tend not to achieve their goals and end the mirror session for reasons unrelated to their goals (e.g., distress or time constraints).
Educating patients about these potentially problematic ‘internal’ goals, and encouraging them to aim for alternative goals (e.g., a fixed length of time, or an external goal defined by visual cues) might help patients to reduce the time they spend looking in the mirror.
The study is limited by the correlational design, the reliance on retrospective reporting, and the lack of a clinical control group.
An investigation of different aspects of overgeneralization in patients with major depressive disorder and borderline personality disorder
Authors: van den Heuvel Thom J. , Derksen Jan J. L. , Eling Paul A. T. M. , van der Staak Cees P. F. 
Published: April 2012

Objective. The aim of this study was to investigate whether (a) overgeneralization is restricted to negative attributions directed at the self; or whether it also extends to positive self‐attributions and to attributions of situations in the outside world, and (b) whether the valence and direction (positively or negatively, to the self‐ or across situations) of overgeneralization processes vary among different patient populations.Methods. Patients with major depressive disorder (MDD, n = 34), borderline personality disorder (BPD, n = 18), or both (n = 35), and never‐depressed non‐patients (NPs; n = 50) completed various measures of overgeneralization.Results. Patients with MDD show higher levels of negative overgeneralization but lower levels of positive overgeneralization to the self‐ and across situations than NPs. Patients with MDD show more negative than positive overgeneralization to the self: a negative bias. They, however, do show higher levels of positive than negative overgeneralization across situations. Patients with BPD show the same pattern for overgeneralization to the self, but their higher levels of negative overgeneralization across situations are not exceeded by their positive counterpart.Conclusions. Results indicate that patient groups differ from NPs not only with respect to negative, but also with respect to positive overgeneralization. Furthermore, the valence and direction of overgeneralization processes vary among MDD and BPD patient populations. More specifically, findings suggest that, as compared to never‐depressed individuals, patients with BPD and patients with MDD alike, lack a buffer against negative overgeneralization directed at the self. In patients with BPD, not only the high level of overgeneralization to the self, but also the high level of overgeneralization across situations seems to be problematic, since both types of overgeneralization appear not to be buffered by their positive counterparts.
Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors against the Initial Autocleavage in Gag-Pol Polyprotein Processing
Authors: Davis David A. , Soule Erin E. , Davidoff Katharine S. , Daniels Sarah I. , Naiman Nicole E. , Yarchoan Robert 
Published: April 2012

ABSTRACTInhibitors of HIV protease have proven to be important drugs in combination anti-HIV therapy. These inhibitors were designed to target mature protease and prevent viral particle maturation by blocking Gag and Gag-Pol processing by mature protease. Currently there are few data assessing the ability of these protease inhibitors to block the initial step in autoproteolytic processing of Gag-Pol. This unique step involves the dimerization of two Gag-Pol polyproteins and autocleavage of the Gag-Pol polyprotein by the embedded dimeric protease. We developed a plasmid encoding a modified form of Gag-Pol that can undergo autoprocessing only at the initial cleavage site between p2 and nucleocapsid. Using anin vitrotranscription/translation system, we assessed the ability of six different approved protease inhibitors (darunavir, indinavir, nelfinavir, ritonavir, saquinavir, and tipranavir) to block this initial autocleavage step. Of these inhibitors, darunavir and saquinavir were the most effective. Darunavir and saquinavir were also the most effective at blocking the initial autoprocessing of full-length Gag-Pol in HIV-1-infected T cells. Thus, we have identified at least two HIV-1 protease inhibitors that have activity against the primary autocatalytic step of the embedded HIV-1 protease in Gag-Pol at concentrations that may be attained in HIV-1-infected patients. Due to unique aspects of the initial processing step, it may be possible to develop inhibitors with greater potency against this step, thus halting viral maturation at the earliest stages. The transcription/translation assay could be used to develop more potent inhibitors of this essential first step in viral maturation.
Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria
Authors: Pou Sovitj , Winter Rolf W. , Nilsen Aaron , Kelly Jane Xu , Li Yuexin , Doggett J. Stone , Riscoe Erin W. , Wegmann Keith W. , Hinrichs David J. , Riscoe Michael K. 
Published: April 2012

ABSTRACT

Sontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains of
Plasmodium falciparum in vitro
. We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC
50
s) against drug-sensitive and multidrug-resistant strains and
in vivo
efficacy against patent infections of
Plasmodium yoelii
in mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.
Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan
Authors: Liao Chun-Hsing , Ko Wen-Chien , Lu Jang-Jih , Hsueh Po-Ren 
Published: April 2012

ABSTRACT

A total of 403 nonduplicate isolates of
Clostridium difficile
were collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC
90
of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC
90
of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (
n
= 81, 20.1%) was accompanied by single or multiple mutations in
gyrA
and
gyrB
genes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreported
gyrB
mutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains of
C. difficile
in the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potent
in vitro
activity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns.
Biochemical and Genetic Characterization of Carbapenem-Hydrolyzing β-Lactamase OXA-229 from Acinetobacter bereziniae
Authors: Bonnin Rémy A. , Ocampo-Sosa Alain A. , Poirel Laurent , Guet-Revillet Hélène , Nordmann Patrice 
Published: April 2012

ABSTRACT

Acinetobacter bereziniae
(formerly
Acinetobacter
genomospecies 10) isolate Nec was recovered from a skin sample of a patient hospitalized in Paris, France. It was resistant to penicillins, penicillin-inhibitor combinations, and carbapenems. Cloning and expression in
Escherichia coli
identified the carbapenem-hydrolyzing class D β-lactamase OXA-229, which is weakly related to other oxacillinases (66% amino acid identity with the closest oxacillinase, OXA-58). It hydrolyzed penicillins, oxacillin, and imipenem but not expanded-spectrum cephalosporins. Sequencing of the genetic context of the
bla
OXA-229
gene did not identify an insertion sequence but did identify mutations in the promoter sequences in comparison to the fully susceptible
A. bereziniae
reference strain. The overexpression of
bla
OXA-229
in
A. bereziniae
Nec as a source of carbapenem resistance was identified by quantitative real-time PCR.
Decreased Susceptibility to Noncarbapenem Antimicrobials in Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates in Toronto, Canada
Authors: Lowe Christopher F. , McGeer Allison , Muller Matthew P. , Katz Kevin 
Published: April 2012

ABSTRACT

Retrospective review from 11 Canadian hospitals showed increasing incidence of extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
and
Klebsiella pneumoniae
from 0.12 per 1,000 inpatient days during 2005 to 0.47 per 1,000 inpatient days during 2009. By 2009, susceptibility rates of ESBL-positive
E. coli
/
K. pneumoniae
were as follows: ciprofloxacin, 12.8%/9.0%; TMP/SMX, 32.9%/12.2%; and nitrofurantoin, 83.8%/10.3%. Nosocomial and nonnosocomial ESBL-producing
E. coli
isolates had similar susceptibility profiles, while nonnosocomial ESBL-producing
K. pneumoniae
was associated with decreased ciprofloxacin (
P
= 0.03) and nitrofurantoin (
P
< 0.001) susceptibilities.
Resistance Analysis of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir
Authors: McPhee Fiona , Friborg Jacques , Levine Steven , Chen Chaoqun , Falk Paul , Yu Fei , Hernandez Dennis , Lee Min S. , Chaniewski Susan , Sheaffer Amy K. , Pasquinelli Claudio 
Published: April 2012

ABSTRACT

Asunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) NS3 protease inhibitor demonstrating efficacy in alfa interferon-sparing, direct-acting antiviral dual-combination regimens (together with the NS5A replication complex inhibitor daclatasvir) in patients chronically infected with HCV genotype 1b. Here, we describe a comprehensive
in vitro
genotypic and phenotypic analysis of asunaprevir-associated resistance against genotypes 1a and 1b using HCV replicons and patient samples obtained from clinical studies of short-term asunaprevir monotherapy. During genotype 1a resistance selection using HCV replicons, the primary NS3 protease substitutions identified were R155K, D168G, and I170T, which conferred low- to moderate-level asunaprevir resistance (5- to 21-fold) in transient-transfection susceptibility assays. For genotype 1b, a higher level of asunaprevir-associated resistance was observed at the same selection pressures, ranging from 170- to 400-fold relative to the wild-type control. The primary NS3 protease substitutions identified occurred predominantly at amino acid residue D168 (D168A/G/H/V/Y) and were associated with high-level asunaprevir resistance (16- to 280-fold) and impaired replication capacity. In asunaprevir single-ascending-dose and 3-day multiple-ascending-dose studies in HCV genotype 1a- or 1b-infected patients, the predominant pre-existing NS3 baseline polymorphism was NS3-Q80K. This substitution impacted initial virologic response rates in a single-ascending-dose study, but its effects after multiple doses were more ambiguous. Interestingly, for patient NS3 protease sequences containing Q80 and those containing K80, susceptibilities to asunaprevir were comparable when tested in an enzyme assay. No resistance-associated variants emerged in these clinical studies that significantly impacted susceptibility to asunaprevir. Importantly, asunaprevir-resistant replicons remained susceptible to an NS5A replication complex inhibitor, consistent with a role for asunaprevir in combination therapies.
Nonspecific Effect of Mycograb on Amphotericin B MIC
Authors: Richie D. L. , Ghannoum M. A. , Isham N. , Thompson K. V. , Ryder N. S. 
Published: April 2012

ABSTRACT

Mycograb C28Y is a recombinant human antibody fragment thought to target HSP-90 and potentiate amphotericin B (AMB). Absence of
in vivo
efficacy led us to reevaluate its
in vitro
activity. Interactions between AMB and Mycograb were investigated using a checkerboard design. Addition of Mycograb or various unrelated proteins, including human serum, resulted in similar decreases in the MIC of AMB. Potentiation of AMB by Mycograb appears to be a nonspecific protein effect.
First Identification of OXA-72 Carbapenemase from Acinetobacter pittii in Colombia
Authors: Montealegre Maria Camila , Maya Juan José , Correa Adriana , Espinal Paula , Mojica Maria F. , Ruiz Sory J. , Rosso Fernando , Vila Jordi , Quinn John P. , Villegas Maria Virginia 
Published: April 2012

ABSTRACT

OXA-72 has been reported in few countries around the world. We report the first case in Colombia in an
Acinetobacter pittii
clinical isolate. The arrival of a new OXA, into a country with high endemic resistance, poses a significant threat, especially because the potential for widespread dissemination is considerable.
Dogs of Nomadic Pastoralists in Northern Kenya Are Reservoirs of Plasmid-Mediated Cephalosporin- and Quinolone-Resistant Escherichia coli, Including Pandemic Clone B2-O25-ST131
Authors: Albrechtova Katerina , Dolejska Monika , Cizek Alois , Tausova Dagmar , Klimes Jiri , Bebora Lily , Literak Ivan 
Published: April 2012

ABSTRACT

Resistance in
Escherichia coli
isolates colonizing gastrointestinal tracts of dogs, cats, and their owners in Northern Kenya was investigated with an emphasis on extended-spectrum beta-lactamases (ESBLs). Totals of 47 (22%,
n
= 216), 2 (4%,
n
= 50), and 4 (17%,
n
= 23) CTX-M-15-producing
E. coli
isolates were obtained from dogs, cats, and humans, respectively. CTX-M-15-producing
E. coli
isolates with identical PFGE profiles were detected in animals and humans living in the same area.
The Spiroindolone Drug Candidate NITD609 Potently Inhibits Gametocytogenesis and Blocks Plasmodium falciparum Transmission to Anopheles Mosquito Vector
Authors: van Pelt-Koops J. C. , Pett H. E. , Graumans W. , van der Vegte-Bolmer M. , van Gemert G. J. , Rottmann M. , Yeung B. K. S. , Diagana T. T. , Sauerwein R. W. 
Published: April 2012

ABSTRACT

The global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of
in vitro
assays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of
Plasmodium falciparum
gametocytes
in vitro
in a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the
Anopheles stephensi
mosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different
P. falciparum
transmission stages.
Members of the Francisella tularensis Phagosomal Transporter Subfamily of Major Facilitator Superfamily Transporters Are Critical for Pathogenesis
Authors: Marohn Mark E. , Santiago Araceli E. , Shirey Kari Ann , Lipsky Michael , Vogel Stefanie N. , Barry Eileen M. 
Published: April 2012

ABSTRACT

Francisella tularensis
is the causative agent of tularemia. Due to its aerosolizable nature and low infectious dose,
F. tularensis
is classified as a category A select agent and, therefore, is a priority for vaccine development. Survival and replication in macrophages and other cell types are critical to
F. tularensis
pathogenesis, and impaired intracellular survival has been linked to a reduction in virulence. The
F. tularensis
genome is predicted to encode 31 major facilitator superfamily (MFS) transporters, and the nine-member
Francisella
phagosomal transporter (Fpt) subfamily possesses homology with virulence factors in other intracellular pathogens. We hypothesized that these MFS transporters may play an important role in
F. tularensis
pathogenesis and serve as good targets for attenuation and vaccine development. Here we show altered intracellular replication kinetics and attenuation of virulence in mice infected with three of the nine Fpt mutant strains compared with wild-type (WT)
F. tularensis
LVS. The vaccination of mice with these mutant strains was protective against a lethal intraperitoneal challenge. Additionally, we observed pronounced differences in cytokine profiles in the livers of mutant-infected mice, suggesting that alterations in
in vivo
cytokine responses are a major contributor to the attenuation observed for these mutant strains. These results confirm that this subset of MFS transporters plays an important role in the pathogenesis of
F. tularensis
and suggest that a focus on the development of attenuated Fpt subfamily MFS transporter mutants is a viable strategy toward the development of an efficacious vaccine.
Cj1136 Is Required for Lipooligosaccharide Biosynthesis, Hyperinvasion, and Chick Colonization by Campylobacter jejuni
Authors: Javed Muhammad Afzal , Cawthraw Shaun A. , Baig Abiyad , Li Jianjun , McNally Alan , Oldfield Neil J. , Newell Diane G. , Manning Georgina 
Published: April 2012

ABSTRACT

Campylobacter jejuni
is a major cause of bacterial food-borne enteritis worldwide, and invasion into intestinal epithelial cells is an important virulence mechanism. Recently we reported the identification of hyperinvasive
C. jejuni
strains and created a number of transposon mutants of one of these strains, some of which exhibited reduced invasion into INT-407 and Caco-2 cells. In one such mutant the transposon had inserted into a homologue of
cj1136
, which encodes a putative galactosyltransferase according to the annotation of the
C. jejuni
NCTC11168 genome. In the current study, we investigated the role of
cj1136
in
C. jejuni
virulence, lipooligosaccharide (LOS) biosynthesis, and host colonization by targeted mutagenesis and complementation of the mutation. The
cj1136
mutant showed a significant reduction in invasion into human intestinal epithelial cells compared to the wild-type strain 01/51. Invasion levels were partially restored on complementing the mutation. The inactivation of
cj1136
resulted in the production of truncated LOS, while biosynthesis of a full-length LOS molecule was restored in the complemented strain. The
cj1136
mutant showed an increase in sensitivity to the bile salts sodium taurocholate and sodium deoxycholate and significantly increased sensitivity to polymyxin B compared to the parental strain. Importantly, the ability of the mutant to colonize 1-day-old chicks was also significantly impaired. This study confirms that a putative galactosyltransferase encoded by
cj1136
is involved in LOS biosynthesis and is important for
C. jejuni
virulence, as disruption of this gene and the resultant truncation of LOS affect both colonization
in vivo
and invasiveness
in vitro
.