bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Tulathromycin in Healthy and Neutropenic Mice Challenged Intranasally with Lipopolysaccharide from Escherichia coli
Authors: Villarino N. , Brown S. A. , Martín-Jiménez T. 
Published: May 2012

ABSTRACT

Tulathromycin represents the first member of a novel subclass of macrolides, known as triamilides, approved to treat bovine and swine respiratory disease. The objectives of the present study were to assess the concentration-versus-time profile of tulathromycin in the plasma and lung tissue of healthy and neutropenic mice challenged intranasally with lipopolysaccharide (LPS) from
Escherichia coli
O111:B4. BALB/c mice were randomly allocated into four groups of 40 mice each: groups T-28 (tulathromycin at 28 mg/kg of body weight), T-7, T7-LPS, and T7-LPS-CP (cyclophosphamide). Mice in group T-28 were treated with tulathromycin at 28 mg/kg subcutaneously (s.c.) (time 0 h). The rest of the mice were treated with tulathromycin at 7 mg/kg s.c. (time 0 h). Animals in dose groups T-7-LPS and T7-LPS-CP received a single dose of
E. coli
LPS intranasally at −7 h. Mice in group T7-LPS-CP were also rendered neutropenic with cyclophosphamide (150 mg/kg intraperitoneally) prior to the administration of tulathromycin. Blood and lung tissue samples were obtained from 5 mice from each dose group at each sampling time over 144 h after the administration of tulathromycin. There were not statistical differences in lung tissue concentrations among groups T-7, T-7-LPS, and T7-LPS-CP. For all dose groups, the distribution of tulathromycin in the lungs was rapid and persisted at relatively high levels during 6 days postadministration. The concentration-versus-time profile of tulathromycin in lung tissue was not influenced by the intranasal administration of
E. coli
LPS. The results suggest that in mice, neutrophils may not have a positive influence on tulathromycin accumulation in lung tissue when the drug is administered during either a neutrophilic or a neutropenic state.
Moxifloxacin Population Pharmacokinetics in Patients with Pulmonary Tuberculosis and the Effect of Intermittent High-Dose Rifapentine
Authors: Zvada Simbarashe P. , Denti Paolo , Geldenhuys Hennie , Meredith Sandra , van As Danelle , Hatherill Mark , Hanekom Willem , Wiesner Lubbe , Simonsson Ulrika S. H. , Jindani Amina , Harrison Thomas , McIlleron Helen M. 
Published: May 2012

ABSTRACT
We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.
The Cyclophilin Inhibitor SCY-635 Disrupts Hepatitis C Virus NS5A-Cyclophilin A Complexes
Authors: Hopkins Sam , Bobardt Michael , Chatterji Udayan , Garcia-Rivera Jose A. , Lim Precious , Gallay Philippe A. 
Published: May 2012

ABSTRACT

The nonimmunosuppressive cyclophilin (Cyp) inhibitor SCY-635 blocks hepatitis C virus (HCV) replication both
in vitro
and
in vivo
and represents a novel potent anti-HCV agent. However, its mechanism of action remains to be fully elucidated. A growing body of evidence suggests that cyclophilin A (CypA) is absolutely necessary for HCV replication and that the HCV nonstructural 5A (NS5A) protein serves as a main viral ligand for CypA. In this study, we examined the effect of SCY-635 on HCV replication. Specifically, we asked whether SCY-635 blocks HCV replication by targeting CypA-NS5A interactions. We also investigated the possibility that HCV can escape SCY-635 selection pressure and whether this resistance influences either CypA-NS5A interactions or the dependence of HCV on CypA. We found not only that SCY-635 efficiently inhibits HCV replication, but it is sufficient alone to clear HCV replicon-containing cells. We found that SCY-635 prevents CypA-NS5A interactions in a dose-dependent manner. SCY-635 prevents the contact between CypA and NS5A derived from genotypes 1 to 3. Together, these data suggest that NS5A-CypA interactions control HCV replication and that SCY-635 blocks viral replication by preventing the formation of these complexes. We also found that NS5A mutant proteins found in SCY-635-resistant HCV replicons behave similarly to wild-type NS5A in terms of both CypA binding and SCY-635-mediated dissociation and inhibition of CypA binding. However, the NS5A mutations found in SCY-635-resistant HCV replicons rescued viral replication in CypA-knockdown cells, suggesting that the NS5A mutations, which arose
in vitro
under SCY-635 selection, do not alter the binding affinity of CypA for NS5A. These specific mutations in NS5A eliminate the dependence of HCV RNA replication on the expression of host CypA
Edwardsiella tarda Eta1, an
In Vivo
-Induced Antigen That Is Involved in Host Infection
Authors: Sun Yun , Zheng Wen-Jiang , Hu Yong-Hua , Sun Bo-Guang , Sun Li 
Published: May 2012

ABSTRACT

Edwardsiella tarda
, a Gram-negative bacterium, is a severe fish pathogen that can also infect humans. In this study, we identified, via
in vivo
-induced antigen technology, an
E. tarda
antigen, Eta1, and analyzed its function in a Japanese flounder (
Paralichthys olivaceus
) model. Eta1 is composed of 226 residues and shares homology with putative bacterial adhesins. Quantitative real-time reverse transcriptase (RT)-PCR analysis indicated that when cultured
in vitro
,
eta1
expression was growth phase dependent and reached maximum at mid-logarithmic phase. During infection of flounder lymphocytes,
eta1
expression was drastically increased at the early stage of infection. Compared to the wild type, the
eta1
-defective mutant, TXeta1, was unaffected in growth but exhibited attenuated overall virulence, reduced tissue dissemination and colonization capacity, and impaired ability to invade flounder lymphocytes and to block the immune response of host cells. The lost virulence of TXeta1 was restored when a functional
eta1
gene was reintroduced into the strain. Western blot and immunodetection analyses showed that Eta1 is localized to the outer membrane and exposed on the surface of
E. tarda
and that recombinant Eta1 (rEta1) was able to interact with flounder lymphocytes. Consistent with these observations, antibody blocking of Eta1 inhibited
E. tarda
infection at the cellular level. Furthermore, when used as a subunit vaccine, rEta1 induced strong protective immunity in flounder against lethal
E. tarda
challenge. Taken together, these results indicate that Eta1 is an
in vivo
-induced antigen that mediates pathogen-host interaction and, as a result, is required for optimal bacterial infection.
Efficacy and tolerability of a β-1 selective β blocker, bisoprolol, as a first-line antihypertensive in Indian patients diagnosed with essential hypertension (BRIGHT): an open-label, multicentric observational study
Authors: Channaraya V , Marya R K , Somasundaram M , Mitra Debashish , Tibrewala K D 
Published: May 2012

ObjectivesThis study was aimed to evaluate the efficacy and tolerability of bisoprolol, in Indian patients diagnosed with stage I essential hypertension as first-line drug.DesignThis was an open-label, phase IV, multicentric prospective study.Settings239 outpatient centres across India.ParticipantsAfter ethical approval, patients who were willing to sign informed consent, who are newly diagnosed with JNC VII stage I essential hypertension (systolic blood pressure 140–159 mm Hg or diastolic blood pressure 90–99 mm Hg) and who are prescribed bisoprolol were enrolled in the study. Patients with significant organ disease or complications, women of childbearing age refusing reliable contraceptive method, patients with known contraindications (like symptomatic bradycardia, significant atrioventricular blockade, sick sinus syndrome) and patients with known hypersensitivity reactions to bisoprolol and unwilling patients were excluded.Primary and secondary outcomes measuresThe primary outcome measure was percentage of patients achieving blood pressure (BP) ≤140/90 mm Hg at the end of 12 weeks, while multiple secondary outcome measures were assessed.ResultsOf 2418 patients screened, 2161 patients were recruited (66.64% men, mean age 51.7±9.8 years, smokers 19.19%) and 2131 (96.44%) patients achieved BP control. There was significant reduction in systolic blood pressure (−25.29; SD: 13.22 mm Hg), diastolic blood pressure (−14.14; SD: 7.67 mm Hg) and heart rate (−12/min; SD: 6.15) compared with baseline (all p values <0.05). The median dose of bisoprolol and average period required for the response were 5 mg/day and 33 days, respectively. Bisoprolol was found to be well tolerated in the patients up to 10 mg/day. A total of 1.9% patients showed adverse events, which were mild to moderate in severity without any severe adverse event. None required treatment withdrawal.ConclusionBisoprolol is an effective and safe option to control BP. Thus, it can be used as one of the first-line antihypertensive in Indian patients.
Neural Control of Ventricular Rate in Ambulatory Dogs With Pacing-Induced Sustained Atrial Fibrillation
Authors: Park Hyung-Wook , Shen Mark J. , Han Seongwook , Shinohara Tetsuji , Maruyama Mitsunori , Lee Young-Soo , Shen Changyu , Hwang Chun , Chen Lan S. , Fishbein Michael C. , Lin Shien-Fong , Chen Peng-Sheng 
Published: May 2012

Background—
We hypothesize that inferior vena cava–inferior atrial ganglionated plexus nerve activity (IVC-IAGPNA) is responsible for ventricular rate (VR) control during atrial fibrillation (AF) in ambulatory dogs.

Methods and Results—

We recorded bilateral cervical vagal nerve activity (VNA) and IVC-IAGPNA during baseline sinus rhythm and during pacing-induced sustained AF in 6 ambulatory dogs. Integrated nerve activities and average VR were measured every 10 seconds over 24 hours. Left VNA was associated with VR reduction during AF in 5 dogs (from 211 bpm [95% CI, 186–233] to 178 bpm [95% CI, 145–210];
P
<0.001) and right VNA in 1 dog (from 208 bpm [95% CI, 197–223] to 181 bpm [95% CI, 163–200];
P
<0.01). There were good correlations between IVC-IAGPNA and left VNA in the former 5 dogs and between IVC-IAGPNA and right VNA in the last dog. IVC-IAGPNA was associated with VR reduction in all dogs studied. Right VNA was associated with baseline sinus rate reduction from 105 bpm (95% CI, 95–116) to 77 bpm (95% CI, 64–91;
P
<0.01) in 4 dogs, whereas left VNA was associated with sinus rate reduction from 111 bpm (95% CI, 90–1250) to 81 bpm (95% CI, 67–103;
P
<0.01) in 2 dogs.

Conclusions—
IVC-IAGPNA is invariably associated with VR reduction during AF. In comparison, right or left VNA was associated with VR reduction only when it coactivates with the IVC-IAGPNA. The vagal nerve that controls VR during AF may be different from that which controls sinus rhythm.
Short- and Long-Term Outcomes With Drug-Eluting and Bare-Metal Coronary Stents
Authors: Bangalore Sripal , Kumar Sunil , Fusaro Mario , Amoroso Nicholas , Attubato Michael J. , Feit Frederick , Bhatt Deepak L. , Slater James 
Published: May 2012

Background—
Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined.

Methods and Results—
PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration–approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (≤1 year) and long-term efficacy (target-vessel revascularization, target-lesion revascularization) and safety (death, myocardial infarction, stent thrombosis) outcomes were evaluated and trial-level data pooled by both mixed-treatment comparison and direct comparison analyses. From 76 randomized clinical trials with 117 762 patient-years of follow-up, compared with BMS, each DES reduced long-term target-vessel revascularization (39%–61%), but the magnitude varied by DES type (EES∼SES∼ZES-R>PES∼ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35–0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent.

Conclusions—
DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent.
Increasing prevalence of ESBL production among Irish clinical Enterobacteriaceae from 2004 to 2008: an observational study
Authors: Fennell Jérôme , Vellinga Akke , Hanahoe Belinda , Morris Dearbhaile , Boyle Fiona , Higgins Francis , Lyons Maura , O’Connell Karina , Keady Deirbhile , Cormican Martin 
Published: May 2012

Abstract

Background
Extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae infections are associated with delayed initiation of appropriate treatment, poor outcomes and increased hospital stay and expense. Although initially associated with healthcare settings, more recent international reports have shown increasing isolation of ESBLs in the community. Both hospital and community ESBL epidemiology in Ireland are poorly defined.

Methods
This report describes clinical and laboratory data from three hospitals over 4.5 years. All significant isolates of Enterobacteriaceae were subjected to standardized antimicrobial susceptibility testing and screening for ESBL production. Available patient data from hospital databases were reviewed.

Results
The database included 974 ESBL producing organisms from 464 patients. Urine and blood isolates represented 84% and 3% of isolates respectively. E. coli predominated (90.9%) followed by K. pneumoniae (5.6%). The majority of patients (n = 246, 53.0%) had been admitted to at least one of the study hospitals in the year prior to first isolation of ESBL. The overall 30-day all-cause mortality from the date of culture positivity was 9.7% and the 1 year mortality was 61.4%. A Cox regression analysis showed age over 60, male gender and previous hospital admissions were significant risk factors for death within 30 days of ESBL isolation. Numbers of ESBL-producing E. coli isolated from urine and blood cultures increased during the study. Urine isolates were more susceptible than blood isolates. Co-resistance to other classes of antimicrobial agents was more common in ESBL producers from residents of long stay facilities (LSF) compared with hospital inpatients who lived at home.

Conclusions
This work demonstrates a progressively increasing prevalence of ESBL Enterobacteriaceae in hospital, LSF and community specimens in a defined catchment area over a long time period . These results will improve clinician awareness of this problem and guide the development of empiric antimicrobial regimens for community acquired bloodstream and urinary tract infections.
Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma
Authors: Romilda Cardin , Marika Piciocchi , Alessandro Sinigaglia , Enrico Lavezzo , Marina Bortolami , Andromachi Kotsafti , Umberto Cillo , Giacomo Zanus , Claudia Mescoli , Massimo Rugge , Fabio Farinati 
Published: May 2012

AbstractBackgroundMicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS), host’s repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death.MethodsTissue samples obtained either at surgery, [neoplastic (HCC) and adjacent non-cancerous cirrhotic tissues (NCCT)] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy) were analysed for 8-OHdG (HPLC-ED), OGG1 (a DNA repair gene) polymorphism (PCR-RFLP), telomerase activity, telomere length (T/S, by RT-PCR), Taqman microRNA assay and Bad/Bax mRNA (RT-PCR). Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues), 22 from chronic hepatitis (CH) and 10 controls (cholecystectomy patients - CON) were examined.ResultsEight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001). Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002); conversely T/S was significantly lower in HCC (p=0.05). MiR-199a-b, -195, -122, -92a and −145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA.ConclusionsThe above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS-mediated oxidative DNA damage, and suggest that this correlates with induction of telomerase activity and, as a novel finding, with over-expression of miR-92, a microRNA that plays a role in both the apoptotic process and in cellular proliferation pathways.
Retro-mode imaging and fundus autofluorescence with scanning laser ophthalmoscope of retinal dystrophies
Authors: Maurizio Battaglia Parodi , Pierluigi Iacono , Stelios Kontadakis , Stefano Vergallo , Marialucia Cascavilla , Ilaria Zucchiatti , Francesco Bandello 
Published: May 2012

Abstract

Background
Retinal dystrophies display a considerably wide range of phenotypic variability, which can make diagnosis and clinical staging difficult. The aim of the study is to analyze the contribution of retro-mode imaging (RMI) and fundus autofluorescence (FAF) to the characterization of retinal dystrophies.

Methods
Eighteen consecutive patients affected by retinal dystrophies underwent a complete ophthalmological examination, including best corrected visual acuity with ETDRS charts, blue-light fundus autofluorescence, (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), and RMI. The primary outcome was the identification of abnormal patterns on RMI. The secondary outcome was the correlation with the findings on BL-FAF and NIR-FAF.

Results
Overall, the main feature of RMI is represented by a pseudo-3D pattern of all the lesions at the posterior pole. More specifically, any accumulation of material within the retina appears as an area of elevation of different shape and size, displaying irregular and darker borders. No precise correlations between RMI, BL-AF, and NIR-AF imaging was found.

Conclusions
RMI and FAF appear to be useful tools for characterizing retinal dystrophies. Non-invasive diagnostic tools may yield additional information on the clinical setting and the monitoring of the patients.
Experience with using second life for medical education in a family and community medicine education unit
Authors: Melús-Palazón Elena , Bartolomé-Moreno Cruz , Palacín-Arbués Juan Carlos , Lafuente-Lafuente Antonio , García Inmaculada García , Guillen Sara , Esteban Ana B , Clemente Silvia , Marco Ángeles M , Gargallo Pilar M , López Carlos , Magallón-Botaya Rosa 
Published: May 2012

Abstract

Background
The application of new technologies to the education of health professionals is both a challenge and a necessity. Virtual worlds are increasingly being explored as a support for education. Aim: The aim of this work is to study the suitability of Second Life (SL) as an educational tool for primary healthcare professionals.

Methods
Design: Qualitative study of accredited clinical sessions in SL included in a continuing professional development (CPD) programme for primary healthcare professionals. Location: Zaragoza I Zone Family and Community Medicine Education Unit (EU) and 9 health centres operated by the Aragonese Health Service, Aragon, Spain. Method: The EU held two training workshops in SL for 16 healthcare professionals from 9 health centres by means of two workshops, and requested them to facilitate clinical sessions in SL. Attendance was open to all personnel from the EU and the 9 health centres. After a trail period of clinical sessions held at 5 health centres between May and November 2010, the CPD-accredited clinical sessions were held at 9 health centres between February and April 2011. Participants: 76 healthcare professionals attended the CPD-accredited clinical sessions in SL. Main measurements: Questionnaire on completion of the clinical sessions.

Results
Response rate: 42-100%. Questionnaire completed by each health centre on completion of the CPD-accredited clinical sessions: Access to SL: 2 centres were unable to gain access. Sound problems: 0% (0/9). Image problems: 0% (0/9). Voice/text chat: used in 100% (10/9); 0 incidents. Questionnaire completed by participants in the CPD-accredited clinical sessions: Preference for SL as a tool: 100% (76/76). Strengths of this method: 74% (56/76) considered it eliminated the need to travel; 68% (52/76) believed it made more effective use of educational resources; and 47% (36/76) considered it improved accessibility. Weaknesses: 91% (69/76) experienced technical problems, while; 9% (7/76) thought it was impersonal and with little interaction. 65.79% (50/76) believed it was better than other distance learning methods and 38.16% (29/76) believed it was better than face-to-face learning.

Conclusions
SL is a tool that allows educational activities to be designed that involve a number of health centres in different geographical locations, consequently eliminating the need to travel and making more effective use of educational resources.