bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Ginkgo biloba extract on the pharmacokinetics and pharmacodynamics of tolbutamide in protein-restricted rats
Authors: Taki Yuko , Hagiwara Eri , Hirose Chiemi , Shinozuka Kazumasa , Umegaki Keizo , Yamada Shizuo 
Published: July 2011

Abstract

Objectives
Effects of repeated administration of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide were examined in rats fed a low-protein diet.

Methods
Rats were given a low (7% casein) or control (20% casein) protein diet for 21 days and administered Ginkgo biloba extract (100 mg/kg per day) for the last 5 days. Tolbutamide was co-administered on the last day. Blood glucose and plasma tolbutamide concentrations were determined over the subsequent 12 h and the activity of hepatic cytochrome P450s were determined at 12 h after dosing.

Key findings
There were significant decreases in body weight, the ratio of liver to body weight, and plasma albumin concentrations in rats on the low-protein diet compared with controls. The hypoglycaemic effect of tolbutamide was significantly greater and the concentration of the drug in plasma was higher in the former group. The repeated administration of Ginkgo biloba extract had little influence on the hypoglycaemic effect of tolbutamide, but tended to decrease the drug concentration in plasma of control rats, while it reduced significantly the hypoglycaemic action and plasma concentration of tolbutamide in the protein-restricted rats.

Conclusions
The effects of Ginkgo biloba extract on the pharmacokinetics and pharmacodynamics of tolbutamide were significantly enhanced in rats on the low-protein diet.
Why does genetic causal information alter perceived treatment effectiveness? An analogue study
Authors: Wright Alison J. , Sutton Stephen R. , Hankins Matthew , Whitwell Sophia C.L. , Macfarlane Angela , Marteau Theresa M. 
Published: July 2011

Objectives.  When a health problem is perceived as having a genetic cause, this appears to increase the perceived effectiveness of pharmacological treatments and reduce perceived effectiveness of non‐pharmacological treatments. Potential mediators of this effect include causal attributions, perceived severity, and perceived control over the health problem. This study aimed to use experimental methods to establish which beliefs mediate the effect of genetic causal information on perceived effectiveness of treatments.Design. A 4(cause: environmental, family history, genetic test, family history & genetic test)×2(severity: higher or low) between‐subjects design using vignettes about heart disease risk, obesity or depression.Methods.  A total of 647 adults, randomly assigned to read one of the experimental vignettes, were interviewed. Key outcomes were perceived effectiveness of medication and of non‐pharmacological treatments. Potential mediators of perceived severity, perceived controllability, and causal attributions were also assessed.Results.  For heart disease risk, genetic causes reduced perceived effectiveness of non‐pharmacological treatments (an effect mediated by causal attributions and perceived control) but did not influence perceived medication effectiveness. For obesity, neither severity nor cause influenced the perceived effectiveness of either treatment. For depression, genetic causes only increased perceived effectiveness of medication for more severe depression, an effect mediated by perceived control.Conclusions.  The impact of genetic causal information on perceived effectiveness of treatments varies with type of health problem. When genetic causal information influences perceived treatment effectiveness, it does so by altering causal attributions and perceived controllability. However, these effects are small and unlikely to translate into clinically meaningful differences in health‐enhancing behaviours.
‘Waste the waist’: The development of an intervention to promote changes in diet and physical activity for people with high cardiovascular risk
Authors: Gillison Fiona , Greaves Colin , Stathi Afroditi , Ramsay Rosemary , Bennett Paul , Taylor Gordon , Francis Margaret , Chandler Roger 
Published: July 2011

Objectives. To identify an evidence‐based intervention to promote changes in diet and physical activity and adapt it for a UK primary care setting for people with high cardiovascular risk.Design. A three‐stage mixed‐methods design was used to facilitate a strategic approach to programme selection and adaptation.Method. Stage 1: Criteria for scientific quality and local appropriateness were developed for the selection/adaptation of an intervention to promote lifestyle change in people of high cardiovascular risk through (1) patient interviews, (2) a literature search to extract evidence‐based criteria for behavioural interventions, and (3) stakeholder consultation. Stage 2: Potential interventions for adaptation were identified and ranked according to their performance against the criteria developed in Stage 1. Stage 3: Intervention mapping (IM) techniques were used to (1) specify the behavioural objectives that participants would need to reach in order to attain programme outcomes, and (2) adapt the selected intervention to ensure that evidence‐based strategies to target all identified behavioural objectives were included.Results. Four of 23 potential interventions identified met the 11 essential criteria agreed by a multi‐disciplinary stakeholder committee. Of these, the Greater Green Triangle programme (Laatikainenet al., 2007) was ranked highest and selected for adaptation. The IM process identified 13 additional behaviour change strategies that were used to adapt the intervention for the local context.Conclusions. IM provided a useful set of techniques for the systematic adaptation of an existing lifestyle intervention to a new population and context, and facilitated transparent working processes for a multi‐disciplinary team.
The transmission of attitudes towards food: Twofold specificity of similarities with parents and friends
Authors: Guidetti Margherita , Conner Mark , Prestwich Andrew , Cavazza Nicoletta 
Published: July 2011

Objectives. The present study explored whether similarity of students’ food attitudes with those of their parents and friends varies as a function of both the food and type of measurement. We expected greater resemblance with parents for attitudes towards fruit and for implicit attitudes and greater resemblance with friends for attitudes towards snacks and for explicit attitudes.Design. We compared the resemblance in implicit and explicit attitudes towards fruit and preference for sweet over savoury snacks between target‐parent and target‐friend pairings. The parental‐peer mutual influence effect was separated from cultural effect by comparing real and random dyads.Methods. Target participants were 85 students who recruited one parent and one best friend each. All participants completed online two Implicit Association Tests and rated their liking for fruit and sweet/savoury snacks.Results. Our target participants’ attitudes towards fruit were predicted by those of their parents rather than friends, with this relationship being detected through implicit but not explicit measures. Conversely, target participants’ preference for sweet over savoury snacks was predicted with those of their friends but not parents, with this relationship being detected through explicit but not implicit measures.Conclusions. Young adults’ resemblance to parents and friends, in terms of food attitudes, seems specific both to the food type and to the attitude measure, suggesting that parents’ influence concerns healthy food and is exerted at an implicit attitude level; whereas friends’ influence concerns junk food and is exerted at an explicit attitude level. The theoretical and practical implications are discussed.
Distant and New Mutations in CTX-M-1 β-Lactamase Affect Cefotaxime Hydrolysis
Authors: Pérez-Llarena Francisco José , Kerff Frédéric , Abián Olga , Mallo Susana , Fernández María Carmen , Galleni Moreno , Sancho Javier , Bou Germán 
Published: July 2011

ABSTRACT

The CTX-M β-lactamases are an increasingly prevalent group of extended-spectrum β-lactamases (ESBL). Point mutations in CTX-M β-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M β-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 β-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the
103
VNYN
106
loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues—Thr71Ile, Met135Ile, Arg164His, and Asn244Asp—that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M β-lactamases, five of which are in positions distant from the catalytic center.
In Vivo
Synergism of Ceftobiprole and Vancomycin against Experimental Endocarditis Due to Vancomycin-Intermediate Staphylococcus aureus
Authors: Entenza J. M. , Veloso T. R. , Vouillamoz J. , Giddey M. , Majcherczyk P. , Moreillon P. 
Published: July 2011

ABSTRACT

The efficacy of ceftobiprole combined with vancomycin was tested against two vancomycin-intermediate
Staphylococcus aureus
(VISA) strains, PC3 and Mu50, in rats with experimental endocarditis. Animals with infected aortic vegetations were treated for 3 days with doses simulating the kinetics after intravenous administration in humans of (i) the standard dose of ceftobiprole of 500 mg every 12 h (b.i.d.) (SD-ceftobiprole), (ii) a low dose of ceftobiprole of 250 mg b.i.d. (LD-ceftobiprole), (iii) a very low dose of ceftobiprole of 125 mg b.i.d. (VLD-ceftobiprole), (iv) SD-vancomycin of 1 g b.i.d., or (v) LD- or VLD-ceftobiprole combined with SD-vancomycin. Low dosages of ceftobiprole were purposely used to highlight positive drug interactions. Treatment with SD-ceftobiprole sterilized 12 of 14 (86%) and 10 of 13 (77%) vegetations infected with PC3 and Mu50, respectively (
P
< 0.001 versus controls). In comparison, LD-ceftobiprole sterilized 10 of 11 (91%) vegetations infected with PC3 (
P
< 0.01 versus controls) but only 3 of 12 (25%) vegetations infected with Mu50 (
P
> 0.05 versus controls). VLD-ceftobiprole and SD-vancomycin alone were ineffective against both strains (≤8% sterile vegetations). In contrast, the combination of VLD-ceftobiprole and SD-vancomycin sterilized 7 of 9 (78%) and 6 of 14 (43%) vegetations infected with PC3 and Mu50, respectively, and the combination of LD-ceftobiprole and SD-vancomycin sterilized 5 of 6 (83%) vegetations infected with Mu50 (
P
< 0.05 versus controls and monotherapy). Thus, ceftobiprole monotherapy simulating standard therapeutic doses was active against VISA experimental endocarditis. Moreover, subtherapeutic LD- and VLD-ceftobiprole synergized with ineffective vancomycin to restore efficacy. Hence, combining ceftobiprole with vancomycin broadens the therapeutic margin of these two compounds against VISA infections.
First Description of an Escherichia coli Strain Producing NDM-1 Carbapenemase in Spain
Authors: Solé Mar , Pitart Cristina , Roca Ignasi , Fàbrega Anna , Salvador Pilar , Muñoz Laura , Oliveira Inés , Gascón Joaquim , Marco Francesc , Vila Jordi 
Published: July 2011

ABSTRACT

A carbapenem-resistant
Escherichia coli
strain (DVR22) was recovered from a stool specimen from a patient with traveler's diarrhea who had traveled to India. Molecular screening led to the first identification of NDM-1 in Spain. The
bla
NDM-1
gene was located in a conjugative plasmid of ca. 300 kb that also contained the
bla
CTX-M-15
,
bla
TEM-1
, Δ
bla
DHA-1
, and
armA
genes. In addition,
bla
NDM-1
was preceded by an IS
Aba125
insertion element only found in
Acinetobacter
spp.
Phylogenetic Sequence Variations in Bacterial rRNA Affect Species-Specific Susceptibility to Drugs Targeting Protein Synthesis
Authors: Akshay Subramanian , Bertea Mihai , Hobbie Sven N. , Oettinghaus Björn , Shcherbakov Dimitri , Böttger Erik C. , Akbergenov Rashid 
Published: July 2011

ABSTRACT

Antibiotics targeting the bacterial ribosome typically bind to highly conserved rRNA regions with only minor phylogenetic sequence variations. It is unclear whether these sequence variations affect antibiotic susceptibility or resistance development. To address this question, we have investigated the drug binding pockets of aminoglycosides and macrolides/ketolides. The binding site of aminoglycosides is located within helix 44 of the 16S rRNA (A site); macrolides/ketolides bind to domain V of the 23S rRNA (peptidyltransferase center). We have used mutagenesis of rRNA sequences in
Mycobacterium smegmatis
ribosomes to reconstruct the different bacterial drug binding sites and to study the effects of rRNA sequence variations on drug activity. Our results provide a rationale for differences in species-specific drug susceptibility patterns and species-specific resistance phenotypes associated with mutational alterations in the drug binding pocket.
Infectious Diseases in Patients with IRAK-4, MyD88, NEMO, or IκBα Deficiency
Authors: Picard Capucine , Casanova Jean-Laurent , Puel Anne 
Published: July 2011

SUMMARY

Autosomal recessive IRAK-4 and MyD88 deficiencies predispose affected patients to recurrent invasive pyogenic bacterial infection. Both defects result in the selective impairment of cellular responses to Toll-like receptors (TLRs) other than TLR3 and of cellular responses to most interleukin-1 receptors (IL-1Rs), including IL-1R, IL-18R, and IL-33R. Hypomorphic mutations in the X-linked
NEMO
gene and hypermorphic mutations in the autosomal
IKBA
gene cause X-linked recessive and autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) syndromes. Both of these defects impair NF-κB-mediated cellular responses to multiple receptors, including TLRs, IL-1Rs, and tumor necrosis factor receptors (TNF-Rs). They therefore confer a much broader predisposition to infections than that for IRAK-4 and MyD88 deficiencies. These disorders were initially thought to be rare but have now been diagnosed in over 170 patients worldwide. We review here the infectious diseases affecting patients with inborn errors of NF-κB-dependent TLR and IL-1R immunity.
Mycoplasma genitalium: from Chrysalis to Multicolored Butterfly
Authors: Taylor-Robinson David , Jensen Jørgen Skov 
Published: July 2011

SUMMARYThe history, replication, genetics, characteristics (both biological and physical), and factors involved in the pathogenesis ofMycoplasma genitaliumare presented. The latter factors include adhesion, the influence of hormones, motility, possible toxin production, and immunological responses. The preferred site of colonization, together with current detection procedures, mainly by PCR technology, is discussed. The relationships betweenM. genitaliumand various diseases are highlighted. These diseases include acute and chronic nongonococcal urethritis, balanoposthitis, chronic prostatitis, and acute epididymitis in men and urethritis, bacterial vaginosis, vaginitis, cervicitis, pelvic inflammatory disease, and reproductive disease in women. A causative relationship, or otherwise strong association, between several of these diseases andM. genitaliumis apparent, and the extent of this, on a subjective basis, is presented; also provided is a comparison betweenM. genitaliumand two other genital tract-orientated mollicutes, namely,Mycoplasma hominis, the first mycoplasma of human origin to be discovered, andUreaplasmaspecies. Also discussed is the relationship betweenM. genitaliumand infertility and also arthritis in both men and women, as is infection in homosexual and immunodeficient patients. Decreased immunity, as in HIV infections, may enhance mycoplasmal detection and increase disease severity. Finally, aspects of the antimicrobial susceptibility and resistance ofM. genitalium, together with the treatment and possible prevention of mycoplasmal disease, are discussed.
Review and International Recommendation of Methods for Typing Neisseria gonorrhoeae Isolates and Their Implications for Improved Knowledge of Gonococcal Epidemiology, Treatment, and Biology
Authors: Unemo Magnus , Dillon Jo-Anne R. 
Published: July 2011

SUMMARY

Gonorrhea, which may become untreatable due to multiple resistance to available antibiotics, remains a public health problem worldwide. Precise methods for typing
Neisseria gonorrhoeae
, together with epidemiological information, are crucial for an enhanced understanding regarding issues involving epidemiology, test of cure and contact tracing, identifying core groups and risk behaviors, and recommending effective antimicrobial treatment, control, and preventive measures. This review evaluates methods for typing
N. gonorrhoeae
isolates and recommends various methods for different situations. Phenotypic typing methods, as well as some now-outdated DNA-based methods, have limited usefulness in differentiating between strains of
N. gonorrhoeae.
Genotypic methods based on DNA sequencing are preferred, and the selection of the appropriate genotypic method should be guided by its performance characteristics and whether short-term epidemiology (microepidemiology) or long-term and/or global epidemiology (macroepidemiology) matters are being investigated. Currently, for microepidemiological questions, the best methods for fast, objective, portable, highly discriminatory, reproducible, typeable, and high-throughput characterization are
N. gonorrhoeae
multiantigen sequence typing (NG-MAST) or full- or extended-length
porB
gene sequencing. However, pulsed-field gel electrophoresis (PFGE) and Opa typing can be valuable in specific situations, i.e., extreme microepidemiology, despite their limitations. For macroepidemiological studies and phylogenetic studies, DNA sequencing of chromosomal housekeeping genes, such as multilocus sequence typing (MLST), provides a more nuanced understanding.
Onchocerciasis: the Role of Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment
Authors: Tamarozzi Francesca , Halliday Alice , Gentil Katrin , Hoerauf Achim , Pearlman Eric , Taylor Mark J. 
Published: July 2011

SUMMARYThe discovery ofWolbachiaintracellular bacteria within filarial nematodes, includingOnchocerca volvulus, the causative agent of onchocerciasis or “river blindness,” has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminateWolbachia, delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role forWolbachiain transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae.Wolbachiahas also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with theWolbachia-mediated recruitment of mast cells, enhance infectivity. TheWolbachiaactivation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance ofWolbachiasymbiosis in onchocerciasis.
Expert Systems in Clinical Microbiology
Authors: Winstanley Trevor , Courvalin Patrice 
Published: July 2011

SUMMARYThis review aims to discuss expert systems in general and how they may be used in medicine as a whole and clinical microbiology in particular (with the aid of interpretive reading). It considers rule-based systems, pattern-based systems, and data mining and introduces neural nets. A variety of noncommercial systems is described, and the central role played by the EUCAST is stressed. The need for expert rules in the environment of reset EUCAST breakpoints is also questioned. Commercial automated systems with on-board expert systems are considered, with emphasis being placed on the “big three”: Vitek 2, BD Phoenix, and MicroScan. By necessity and in places, the review becomes a general review of automated system performances for the detection of specific resistance mechanisms rather than focusing solely on expert systems. Published performance evaluations of each system are drawn together and commented on critically.
Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum
Authors: Rikihisa Yasuko 
Published: July 2011

SUMMARYAnaplasma phagocytophilumpersists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis.A. phagocytophilumis an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks.A. phagocytophilumevolved the remarkable ability to hijack the regulatory system of host cells.A. phagocytophilumalters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-γ). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlyingA. phagocytophiluminfection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease.
Inactivation of
clpB
in the Pathogen Leptospira interrogans Reduces Virulence and Resistance to Stress Conditions
Authors: Lourdault Kristel , Cerqueira Gustavo M. , Wunder Elsio A. , Picardeau Mathieu 
Published: July 2011

ABSTRACT

Leptospira interrogans
is the causative agent of leptospirosis, which is an emerging zoonotic disease. Resistance to stress conditions is largely uncharacterized for this bacterium. We therefore decided to analyze a
clpB
mutant that we obtained by random transposon mutagenesis. The mutant did not produce any of the two isoforms of ClpB. The
clpB
mutant exhibited growth defects at 30° and 37°C and in poor nutrient medium and showed increased susceptibility to oxidative stress, whereas the genetically complemented strain was restored in ClpB expression and
in vitro
wild-type growth. We also showed that the
clpB
mutant was attenuated in virulence in an animal model of acute leptospirosis. Our findings demonstrate that ClpB is involved in the general stress response. The chaperone is also necessary, either directly or indirectly, for the virulence of the pathogen
L. interrogans
.