bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptidomimetic and Organometallic Derivatives of Primaquine Active against Leishmania infantum
Authors: Vale-Costa Sílvia , Vale Nuno , Matos Joana , Tomás Ana , Moreira Rui , Gomes Paula , Gomes Maria Salomé 
Published: August 2012

ABSTRACT

The current treatment of visceral leishmaniasis is made difficult by the low efficacy, elevated costs, low bioavailability, and high toxicity of many of the available drugs. Primaquine, an antimalarial 8-aminoquinoline, displays activity against
Leishmania
spp., and several of its derivatives have been developed as potential antileishmanial drugs. However, primaquine exhibits low oral bioavailability due to oxidative deamination of its aliphatic chain. We previously developed peptidomimetic and organometallic derivatives of primaquine, with higher resistance to proteolytic degradation and oxidative deamination, which presented significant activity against primaquine-sensitive pathogens such as
Plasmodium
or
Pneumocystis
. In light of these relevant findings, we decided to evaluate these compounds against both the promastigote and intramacrophagic amastigote forms of
Leishmania infantum
, the agent of Mediterranean visceral leishmaniasis. We found that several of these compounds had significant activity against
L. infantum
. One of the peptidomimetic (3c) and one of the organometallic (7a) derivatives of primaquine were active against the clinically relevant intramacrophagic amastigote form of the parasite, causing >96% reductions in the number of amastigotes per 100 macrophages at 60 and 40 μM, respectively, while being less cytotoxic for host cells than the reference drugs sitamaquine and miltefosine. Hence, compounds 3c and 7a represent new entries toward the development of new antileishmanial leads.
Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Linezolid in Patients with Multidrug-Resistant Tuberculosis
Authors: Vu D. H. , Bolhuis M. S. , Koster R. A. , Greijdanus B. , de Lange W. C. M. , van Altena R. , Brouwers J. R. B. J. , Uges D. R. A. , Alffenaar J. W. C. 
Published: August 2012

ABSTRACT
Linezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.
Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy
Authors: Tarning Joel , Chotsiri Palang , Jullien Vincent , Rijken Marcus J. , Bergstrand Martin , Cammas Mireille , McGready Rose , Singhasivanon Pratap , Day Nicholas P. J. , White Nicholas J. , Nosten Francois , Lindegardh Niklas 
Published: August 2012

ABSTRACT

Amodiaquine is effective for the treatment of
Plasmodium vivax
malaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women with
P. vivax
infection and again after delivery. Twenty-seven pregnant women infected with
P. vivax
malaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and without
P. vivax
infections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of complete
in vivo
conversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.
Inhibition of Protein Synthesis on the Ribosome by Tildipirosin Compared with Other Veterinary Macrolides
Authors: Andersen Niels Møller , Poehlsgaard Jacob , Warrass Ralf , Douthwaite Stephen 
Published: August 2012

ABSTRACT

Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including
Mannheimia haemolytica
and
Pasteurella multocida
, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC
50
], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site.
The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague
Authors: Fetherston Jacqueline D. , Mier Ildefonso , Truszczynska Helena , Perry Robert D. 
Published: August 2012

ABSTRACTThe Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. InYersinia pestis, single mutations in eitheryfeorfeoresult in reduced growth under static (limited aeration), iron-chelated conditions, while ayfe feodouble mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. BothfetPand a downstream locus (flpforfetlinkedphenotype) were required for growth of ayfe feo ybtmutant under static, iron-limiting conditions. AnfeoBmutation alone had no effect on the virulence ofY. pestisin either bubonic or pneumonic plague models. Anfeo yfedouble mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD50) relative to the Yfe+Feo+parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of thefeooperon inY. pestis. Under static growth conditions, theY. pestis feo::lacZfusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations infeoC,fnr,arcA,oxyR, orrstABhad no significant effect on transcription of theY. pestis feopromoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.
Host and Bacterial Phenotype Variation in Adhesion of Streptococcus mutans to Matched Human Hosts
Authors: Esberg Anders , Löfgren-Burström Anna , Öhman Ulla , Strömberg Nicklas 
Published: August 2012

ABSTRACT

The commensal pathogen
Streptococcus mutans
uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of
S. mutans
(
n
= 70 isolates) from caries and caries-free human extremes (
n
= 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of
S. mutans
Ingbritt and matched isolates and saliva samples correlated (
r
= 0.929), suggesting that the host specify about four-fifths (
r
2
= 0.86) of the variation in matched adhesion. Half of the variation in
S. mutans
Ingbritt adhesion to saliva from the caries cases-controls (
n
= 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B
1
, and B
2
) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B
1
and B
2
tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in
S. mutans
adhesion than anticipated previously.
Genome Sequence of Lactococcus garvieae IPLA 31405, a Bacteriocin-Producing, Tetracycline-Resistant Strain Isolated from a Raw-Milk Cheese
Authors: Flórez Ana Belén , Reimundo Pilar , Delgado Susana , Fernández Elena , Alegría Ángel , Guijarro José A. , Mayo Baltasar 
Published: August 2012

ABSTRACTThis work describes the draft genome sequence ofLactococcus garvieaeIPLA 31405, isolated from a traditional Spanish cheese. The genome contains a lactose-galactose operon, a bacteriocin locus, two integrated phages, a transposon harboring an activetet(M) gene, and two theta-type plasmid replicons. Genes encoding virulence factors were not recorded.
Genome Sequence ofn-Alkane-Degrading Hydrocarboniphaga effusa Strain AP103T(ATCC BAA-332T)
Authors: Chang Hung-Kuang , Zylstra Gerben J. , Chae Jong-Chan 
Published: August 2012

ABSTRACTHydrocarboniphaga effusastrain AP103T(ATCC BAA-332T) is a member of theGammaproteobacteriautilizingn-alkanes as the sole source of carbon and energy. Here we report the draft genome sequence of AP103T, which consists of 5,193,926 bp with a G + C content of 65.18%.
Draft Genome Sequence of the Human Pathogen Halomonas stevensii S18214T
Authors: Kim Kwang Kyu , Lee Keun Chul , Jeong Haeyoung , Stevens David A. , Lee Jung-Sook 
Published: August 2012

ABSTRACTHalomonas stevensiiis a Gram-negative, moderately halophilic bacterium causing environmental contamination and infections in a dialysis center. Here we present the 3.7-Mb draft genome sequence of the type strain (S18214T) ofH. stevensii, which will give insight into the pathogenic potential ofH. stevensii.
Genome Sequence of Enterococcus hirae (Streptococcus faecalis) ATCC 9790, a Model Organism for the Study of Ion Transport, Bioenergetics, and Copper Homeostasis
Authors: Gaechter Thomas , Wunderlin Christof , Schmidheini Tobias , Solioz Marc 
Published: August 2012

ABSTRACTEnterococcus hiraeATCC 9790 is a Gram-positive lactic acid bacterium that has been used in basic research for over 4 decades. Here we report the sequence and annotation of the 2.8-Mb genome ofE. hiraeand its endemic 29-kb plasmid pTG9790.
Complete Genome Sequence of Streptococcus agalactiae ZQ0910, a Pathogen Causing Meningoencephalitis in the GIFT Strain of Nile Tilapia (Oreochromis niloticus)
Authors: Wang Bei , Jian Jichang , Lu Yishan , Cai Shuanghu , Huang Yuchong , Tang Jufen , Wu Zaohe 
Published: August 2012

ABSTRACTStreptococcus agalactiae(group B streptococcus [GBS]) is a pathogen that causes meningoencephalitis in Nile tilapia (Oreochromis niloticus). Here, we reported the complete genome sequence ofS. agalactiaestrain ZQ0910, which was isolated from the GIFT strain of Nile tilapia in Guangdong, China.
Genome Sequence of a Neisseria meningitidis Capsule Null Locus Strain from the Clonal Complex of Sequence Type 198
Authors: Schork Sabine , Schlüter Andreas , Blom Jochen , Schneiker-Bekel Susanne , Pühler Alfred , Goesmann Alexander , Frosch Matthias , Schoen Christoph 
Published: August 2012

ABSTRACTNeisseria meningitidisis a commensal and accidental pathogen exclusively of humans. Although the production of polysaccharide capsules is considered to be essential for meningococcal virulence, there have been reports of constitutively unencapsulated strains causing invasive meningococcal disease (IMD). Here we report the genome sequence of a capsule null locus (cnl) strain of sequence type 198 (ST-198), which is found in half of the reported cases of IMD caused bycnlmeningococcal strains.
Draft Genome Sequences of Eight Salmonella enterica Serotype Newport Strains from Diverse Hosts and Locations
Authors: Cao Guojie , Zhao Shaohua , Strain Errol , Luo Yan , Timme Ruth , Wang Charles , Brown Eric , Meng Jianghong , Allard Marc 
Published: August 2012

ABSTRACTSalmonellosis is a major contributor to the global public health burden.Salmonella entericaserotype Newport has ranked among threeSalmonellaserotypes most commonly associated with food-borne outbreaks in the United States. It was thought to be polyphyletic and composed of independent lineages. Here we report draft genomes of eight strains ofS. Newport from diverse hosts and locations.
Draft Genome Sequence of Escherichia coli W26, an Enteric Strain Isolated from Cow Feces
Authors: Kim Mincheol , Yi Hana , Cho Yong-Joon , Jang Jeonghwan , Hur Hor-Gil , Chun Jongsik 
Published: August 2012

ABSTRACTAn enteric bacterium,Escherichia coliW26 (KACC 16630), was isolated from feces from a healthy cow in South Korea. Here, we report the draft genome sequence of the isolate, which is closely affiliated with commensal strains belonging toE. coliphylogroup B1.
Draft Genome Sequence of Brevibacterium massiliense Strain 541308T
Authors: Roux Véronique , Robert Catherine , Gimenez Grégory , Raoult Didier 
Published: August 2012

ABSTRACTA draft genome sequence ofBrevibacterium massiliense, an aerobic bacterium isolated from a human ankle discharge, is described here. CRISPR-associated proteins were found to be encoded in the genome, and analysis of transport proteins was performed.
Complete Genome Sequence of the Naphthalene-Degrading Pseudomonas putida Strain ND6
Authors: Li Shanshan , Zhao Huabing , Li Yaxiao , Niu Shumin , Cai Baoli 
Published: August 2012

ABSTRACTPseudomonas putidastrain ND6 is an efficient naphthalene-degrading bacterium. The complete genome of strain ND6 was sequenced and annotated. The genes encoding the enzymes involved in catechol degradation by theortho-cleavage pathway were found in the chromosomal sequence, which indicated that strain ND6 is able to metabolize naphthalene by the catecholmeta- andortho-cleavage pathways.
Current practices in determining return to play following head injury in professional football in the UK
Authors: Price Jo , Malliaras Peter , Hudson Zoe 
Published: August 2012

ObjectiveTo investigate the awareness of English football team doctors of the ‘Consensus in Sport’ (CIS) guidelines for the assessment and management of concussion, and to identify adherence to these internationally accepted recommendations.MethodA questionnaire was sent to Club Medical Officers of all the 92 English Football league teams.ResultsThe majority (55.6%) of teams in the English Football Association (FA) do not routinely follow the CIS guidelines. Only 21% of teams routinely record an approved preseason cognitive score and only 42% complete a recommended postconcussion assessment. One-third are still using outdated fixed periods of abstinence following a concussion.ConclusionsFA players are not being treated according to the guidelines recommended by International sporting organisations. The endorsement of the CIS guidelines by the English FA would ensure that all medical teams have a sound and safe protocol for managing concussed players and making return to play decisions.
Association of objectively measured physical activity with established and novel cardiovascular biomarkers in elderly subjects: every step counts
Authors: Klenk Jochen , Denkinger Michael , Nikolaus Thorsten , Peter Richard , Rothenbacher Dietrich , Koenig Wolfgang ,   the ActiFE Study Group
Published: August 2012

ObjectiveTo analyse the relationship between objectively measured daily walking duration and cardiovascular biomarkers of inflammation, cardiac dysfunction and renal impairment.MethodsBetween March 2009 and April 2010, physical activity was assessed in 1253 community-dwelling individuals living in Germany aged ≥65 years (57% men) over 1 week using a thigh-worn accelerometer. C reactive protein (CRP), white blood cells (WBC), N-terminal pro-brain natriuretic peptide, high-sensitive troponin T (hsTnT), creatinine (Cr) and cystatin C (CysC) were also measured. Least-square means of daily walking duration were calculated for quartiles of each biomarker adjusted for sex, age, pre-existing cardiovascular disease and smoking status.ResultsAfter adjustment for covariates, statistically significant linear associations with walking duration were observed for WBC, hsTnT, Cr and CysC. CRP quartiles 1 and 2 showed no significant difference followed by a significant inverse dose–response relationship. A similar pattern, but less pronounced, was seen for N-terminal pro-brain natriuretic peptide. Mean differences between the first two quartiles of CRP and its fourth quartile were 17 min. Between categories 1 (more beneficial) and 4 of WBC, hsTnT, Cr and CysC the differences were 15, 12, 23 and 20 min, respectively.ConclusionIncreased walking duration is associated with a more favourable profile of cardiovascular biomarkers in elderly subjects.
Immune response and protective efficacy of S9 ribosomal protein of Streptococcus pneumoniae in a model of sepsis
Authors: Araújo Helton Fernandes , Campos Patrícia Cota , Camargo Dhian Renato Almeida , Pereira Filippe Nonato Roberto , Samuel Michelle Lara , Oliveira Marluce Aparecida Assunção , Fortes-Dias Consuelo Latorre , Leclercq Sophie Yvette 
Published: August 2012

Vaccination is the most promising strategy to reduce the incidence of pneumococcal infection. Although there are vaccines available, all of them are based on polysaccharide antigens (conjugated or not). In addition to their high cost, those vaccines do not cover all serotypes. To overcome these hindrances, we evaluated the immunogenicity and the protective efficacy of the S9 ribosomal protein of Streptococcus pneumoniae with the aim of developing a protein-based vaccine in the future. The gene encoding the S9 ribosomal protein was cloned in pET21-a expression vector, and the recombinant S9 protein was used to immunize mice. Significantly higher levels of anti-S9 immunoglobulin G were achieved (with predominance of immunoglobulin G1) in comparison with the control. Antibodies elicited against S. pneumoniae protein extract in rabbit recognized the recombinant S9 protein by Western blot, thus demonstrating its immunogenicity. Moreover, mice immunized with recombinant S9 protein and challenged with a virulent strain of S. pneumoniae presented a significant reduction of bacteremia after 24 h of infection as compared with the control. However, in the S9-immunized mice the onset of death was insignificantly delayed, but all of them died by the fourth day postinfection.
Occurrence of clinical isolates ofKlebsiella pneumoniaeharboring chromosomally mediated and plasmid-mediated CTX-M-15 β-lactamase in a Tunisian hospital
Authors: Chouchani Chedly , El Salabi Allaaeddin , Marrakchi Rim , Abouelkacem Nader , Walsh Timothy R. 
Published: August 2012

The spread of multidrug-resistant strains of Klebsiella pneumoniae in hospitals is of concern to clinical microbiologists, health care professionals, and physicians because of the impact infections caused by these bacteria have in causing morbidity and mortality. Clinical isolates of K. pneumoniae have been found to show resistance to third-generation cephalosporins as a result of acquiring extended-spectrum β-lactamase-producing genes, such as blaCTX-M. Since little is known about the mechanisms of antibiotic resistance observed in Kasserine hospital, Tunisia, this study was undertaken to investigate the mechanisms by which clinical isolates of K. pneumoniae resist β-lactam antibiotics. Twelve strains of K. pneumoniae were collected from patients admitted to Kasserine hospital; these isolates showed multiresistance phenotypes. Molecular genetics investigations using polymerase chain reaction, S1 digestion, and pulsed-field gel electrophoresisshowed that blaCTX-M-15in association with ISEcp1 is responsible for the resistance of these strains to third-generation cephalosporins. It has been determined that blaCTX-M-15is chromosomally mediated and plasmid mediated, which alarming need for infection control to prevent the outbreak of such a resistance mechanism.
Microarray-based transcriptome ofListeria monocytogenesadapted to sublethal concentrations of acetic acid, lactic acid, and hydrochloric acid
Authors: Tessema Girum Tadesse , Møretrø Trond , Snipen Lars , Heir Even , Holck Askild , Naterstad Kristine , Axelsson Lars 
Published: August 2012

Listeria monocytogenes , an important foodborne pathogen, commonly encounters organic acids in food-related environments. The transcriptome of L. monocytogenes L502 was analyzed after adaptation to pH 5 in the presence of acetic acid, lactic acid, or hydrochloric acid (HCl) at 25 °C, representing a condition encountered in mildly acidic ready-to-eat food kept at room temperature. The acid-treated cells were compared with a reference culture with a pH of 6.7 at the time of RNA harvesting. The number of genes and magnitude of transcriptional responses were higher for the organic acids than for HCl. Protein coding genes described for low pH stress, energy transport and metabolism, virulence determinates, and acid tolerance response were commonly regulated in the 3 acid-stressed cultures. Interestingly, the transcriptional levels of histidine and cell wall biosynthetic operons were upregulated, indicating possible universal response against low pH stress in L. monocytogenes. The opuCABCD operon, coding proteins for compatible solutes transport, and the transcriptional regulator sigL were significantly induced in the organic acids, strongly suggesting key roles during organic acid stress. The present study revealed the complex transcriptional responses of L. monocytogenes towards food-related acidulants and opens the roadmap for more specific and in-depth future studies.