bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood leucocyte cytokine production after LPS stimulation at different concentrations of glucose and/or insulin
Authors: BEITLAND S. , OPDAHL H. , ASPELIN T. , SAETRE L. , LYBERG T. 
Published: December 2008

Background: Previous studies have indicated that alterations in blood glucose and/or insulin levels modify the inflammatory response. The purpose of this study was to elucidate whether increased levels of glucose and/or insulin influence the activation pattern of blood leucocytes and their production of cytokines in vitro.Methods: Venous blood was obtained from eight healthy male volunteers after an overnight fast. Glucose and/or insulin were added to aliquots of whole blood to increase the blood glucose concentration by 5 or 20 mmol/l and/or the insulin concentration by 6 or 30 nmol/l, respectively, before stimulation with E. coli lipopolysaccharide (LPS) at concentrations of 10, 100 or 1000 ng/ml. The samples were subsequently incubated at 37 °C for 6 h before cytokine measurements. After centrifugation the levels of interleukins (IL)‐1β, IL‐6, IL‐8, IL‐10 and tumour necrosis factor (TNF)‐α were measured in plasma using enzyme‐linked immuno‐sorbent assays. The results were compared with cytokine levels in parallel control samples to which only identical amounts of LPS were added.Results: The LPS‐stimulated production of IL‐1β was significantly reduced by on average 26% in samples to which glucose 20 mmol/l was added; addition of insulin and/or glucose 5 mmol/l had no apparent effect on the IL‐1β production at any LPS concentration. The levels of IL‐6, IL‐8, IL‐10 and TNF‐α were not manifestly altered by addition of glucose and/or insulin at any LPS concentration.Conclusion: A substantial increase in blood glucose concentration changed the IL‐1β production, but not the production of other cytokines, in response to LPS stimulation.
Clobazam in the treatment of Lennox‐Gastaut syndrome
Authors: Conry Joan A. , Ng Yu‐Tze , Paolicchi Juliann M. , Kernitsky Lydia , Mitchell Wendy G. , Ritter Frank J. , Collins Stephen D. , Tracy Katherine , Kormany William N. , Abdulnabi Radhi , Riley Bill , Stolle Julie 
Published: December 2008

SummaryPurpose:  This randomized, double‐blind, dose‐ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox‐Gastaut syndrome (LGS).Methods:  Sixty‐eight patients with LGS aged 2–26 years were administered CLB (low dose = target 0.25 mg/kg/day; high dose = target 1.0 mg/kg/day). The study consisted of 4‐week baseline, 3‐week titration, and 4‐week maintenance periods, followed by a 3‐week taper or continuation in an open‐label study. Seizure frequency was recorded in a diary by the parent/caregiver throughout the study.Results:  Weekly drop seizure rates were significantly reduced from baseline in both the high‐dose and low‐dose groups; the reduction was significantly greater in the high‐dose group. A significantly greater proportion of patients in the high‐dose group experienced reductions in drop seizures of ≥25%, ≥50%, and ≥75% compared to the low‐dose group; more patients in the high‐dose group experienced a 100% reduction, but the difference was not significant. Nondrop seizures were also reduced in a dose‐dependent manner. In both investigator and parent/caregiver global evaluations, patients in the high‐dose group showed significantly greater improvements in overall symptoms compared to low‐dose CLB. Adverse events were generally mild or moderate, and were similar between dose groups. Five serious adverse events were reported in four patients, but in no case was CLB discontinued.Conclusions:  Clobazam was well tolerated and reduced drop seizure rates; high‐dose CLB was more effective than low‐dose CLB. Other seizure types were also reduced.
Association of subjective anxiety, depression, and sleep disturbance with quality‐of‐life ratings in adults with epilepsy
Authors: Kwan Patrick , Yu Evelyn , Leung Howan , Leon Teresa , Mychaskiw Marko A. 
Published: December 2008

SummaryPurpose:  To determine the relative contributions of subjective anxiety, depression, sleep disturbance, and seizure‐related variables to quality‐of‐life scores in adults with epilepsy, and the interrelationships among these factors.Methods:  Consecutive adult patients with epilepsy attending neurology outpatient clinics were recruited. Patients completed the following scales: Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale, Medical Outcomes Study (MOS) Sleep Scale, Epworth Sleepiness Scale, and Quality of Life in Epilepsy Inventory‐31 (QOLIE‐31). Univariate and multivariate linear regression models were used to identify variables associated with QOLIE‐31 overall score. Path analysis model was constructed to test for interrelations between the variables.Results:  Two hundred forty‐seven patients completed the questionnaires. By multivariate analysis, in order of degree of contribution, HADS anxiety subscale score, MOS Sleep Scale Sleep Problems Index score, HADS depression subscale score, number of current antiepileptic drugs used, and seizure freedom in the past 4 weeks, significantly correlated with QOLIE‐31 overall score, accounting for 65.2% of the variance. Complex interrelationships were present between these factors. A general linear model to predict QOLIE‐31 overall score in the presence of these factors was constructed.Conclusion:  Subjective anxiety, depression, and sleep disturbance exerted greater effect than short‐term seizure control on quality of life scores of patients with epilepsy. These factors should be considered simultaneously when evaluating effects of treatment on quality of life.
Fabrication and Characterization of a (100) Three‐Axis‐Oriented Single‐Crystal (Ba0.7Sr0.3)TiO3 Thin Film Prepared by the Chemical Solution Deposition Method
Authors: Hosokura Tadasu , Kageyama Keisuke , Takagi Hiroshi , Sakabe Yukio 
Published: December 2008

Epitaxially grown single‐crystal perovskite (100) three‐axis‐oriented (Ba0.7Sr0.3)TiO3 thin films were prepared on a (100) platinum‐coated (100) magnesium oxide (MgO) single‐crystal substrate by the chemical solution deposition method using a solution derived from Ba(CH3COO)2, Sr(CH3COO)2, and Ti(O‐i‐C3H7)4. The growth of the film was found to depend on the annealing condition. A (Ba,Sr)TiO3 thin film annealed at 1073 K was found to be a single crystal by transmission electron microscope. The single‐crystal film exhibited a (100) three‐axis orientation that followed the (100) orientation of the Pt substrate, as observed from an X‐ray pole figure measurement and selected area electron diffraction patterns.
In Vitro Activity of LK-157, a Novel Tricyclic Carbapenem As Broad-Spectrum β-Lactamase Inhibitor
Authors: Paukner Susanne , Hesse Lars , Preželj Andrej , Šolmajer Tomaž , Urleb Uroš 
Published: December 2008

ABSTRACT

LK-157 is a novel tricyclic carbapenem with potent activity against class A and class C β-lactamases. When tested against the purified TEM-1 and SHV-1 enzymes, LK-157 exhibited 50% inhibitory concentrations (IC
50
s) in the ranges of the clavulanic acid and tazobactam IC
50
s (55 nM and 151 nM, respectively). Moreover, LK-157 significantly inhibited AmpC β-lactamase (IC
50
, 62 nM), as LK-157 was >2,000-fold more potent than clavulanic acid and approximately 28-fold more active than tazobactam. The in vitro activities of LK-157 in combination with amoxicillin, piperacillin, ceftazidime, cefotaxime, ceftriaxone, cefepime, cefpirome, and aztreonam against an array of Ambler class A (TEM-, SHV-, CTX-M-, KPC-, PER-, BRO-, and PC-type)- and class C-producing bacterial strains derived from clinical settings were evaluated in synergism experiments and compared with those of clavulanic acid, tazobactam, and sulbactam. In vitro MICs against ESBL-producing strains (except CTX-M-containing strains) were reduced 2- to >256-fold, and those against AmpC-producing strains were reduced even up to >32-fold. The lowest MICs (≤0.025 to 1.6 μg/ml) were observed for the combination of cefepime and cefpirome with a constant LK-157 concentration of 4 μg/ml, thus raising an interest for further development. LK-157 proved to be a potent β-lactamase inhibitor, combining activity against class A and class C β-lactamases, which is an absolute necessity for use in the clinical setting due to the worldwide increasing prevalence of bacterial strains resistant to β-lactam antibiotics.
Effect of Differences in MIC Values on Clinical Outcomes in Patients with Bloodstream Infections Caused by Gram-Negative Organisms Treated with Levofloxacin
Authors: DeFife Robyn , Scheetz Marc H. , Feinglass Joe M. , Postelnick Michael J. , Scarsi Kimberly K. 
Published: December 2008

ABSTRACT

Emerging evidence suggests that current fluoroquinolone dosing strategies may be inadequate to treat bloodstream infections caused by organisms classified as sensitive. This study sought to determine if differences in MICs for levofloxacin-susceptible gram-negative organisms correlate with differences in patient outcomes. A retrospective cohort study evaluated patients treated with levofloxacin for bloodstream infections caused by susceptible gram-negative organisms. Patients infected with gram-negative organisms for which MICs indicated susceptibility were categorized into three groups: those with organisms for which MICs were low (≤0.25 mg/liter), intermediate (0.5 mg/liter), and high (1 or 2 mg/liter). Patients were evaluated for baseline similarity, all-cause mortality, and measurements of morbidity. A total of 404 patients with bloodstream infections caused by gram-negative organisms were identified. Of these patients, 312 were treated with levofloxacin and included in the analysis. No significant difference in all-cause mortality among the three groups was observed. The high-MIC group had a significantly longer average hospital stay postculture than the low- and intermediate-MIC groups (16.4 days versus 7.3 and 7.9 days;
P
< 0.01) and a significantly longer duration of infection (2.1 days versus 1.0 and 1.2 days;
P
< 0.001). Multivariate analysis adjusting for covariates revealed that a high MIC was associated with an increase of 5.67 days (95% confidence interval, 0.77 to 10.62 days;
P
= 0.02) in the mean length of stay postculture compared to the mean length of stay for the low-MIC group. Patients treated with levofloxacin for bloodstream infections caused by gram-negative organisms for which MICs were elevated, yet still in the susceptible category, had worse outcomes than similar patients infected with organisms for which MICs were lower. In vitro susceptibility classifications of fluoroquinolones for the treatment of bloodstream infections caused by gram-negative organisms require further study.
Population Pharmacokinetic Analysis of Voriconazole Plasma Concentration Data from Pediatric Studies
Authors: Karlsson Mats O. , Lutsar Irja , Milligan Peter A. 
Published: December 2008

ABSTRACT

Voriconazole is a potent triazole with broad-spectrum antifungal activity against clinically significant and emerging pathogens. The present population pharmacokinetic analysis evaluated voriconazole plasma concentration-time data from three studies of pediatric patients of 2 to <12 years of age, incorporating a range of single or multiple intravenous (i.v.) and/or oral (p.o.) doses. An appropriate pharmacokinetic model for this patient population was created using the nonlinear mixed-effect modeling approach. The final model described voriconazole elimination by a Michaelis-Menten process and distribution by a two-compartment model. It also incorporated a statistically significant (
P
< 0.001) influence of the CYP2C19 genotype and of the alanine aminotransferase level on clearance. The model was used in a number of deterministic simulations (based on various fixed, mg/kg of body weight, and individually adjusted doses) aimed at finding suitable i.v. and p.o. voriconazole dosing regimens for pediatric patients. As a result, 7 mg/kg twice a day (BID) i.v. or 200 mg BID p.o., irrespective of body weight, was recommended for this patient population. At these doses, the pediatric area-under-the-curve (AUC) distribution exhibited the least overall difference from the adult AUC distribution (at dose levels used in clinical practice). Loading doses or individual dosage adjustments according to baseline covariates are not considered necessary in administering voriconazole to children.
Linezolid Alone or Combined with Rifampin against Methicillin-Resistant
Staphylococcus aureus
in Experimental Foreign-Body Infection
Authors: Baldoni Daniela , Haschke Manuel , Rajacic Zarko , Zimmerli Werner , Trampuz Andrej 
Published: December 2008

ABSTRACT

We investigated the activity of linezolid, alone and in combination with rifampin (rifampicin), against a methicillin-resistant
Staphylococcus aureus
(MRSA) strain in vitro and in a guinea pig model of foreign-body infection. The MIC, minimal bactericidal concentration (MBC) in logarithmic phase, and MBC in stationary growth phase were 2.5, >20, and >20 μg/ml, respectively, for linezolid; 0.01, 0.08, and 2.5 μg/ml, respectively, for rifampin; and 0.16, 0.63, >20 μg/ml, respectively, for levofloxacin. In time-kill studies, bacterial regrowth and the development of rifampin resistance were observed after 24 h with rifampin alone at 1× or 4× the MIC and were prevented by the addition of linezolid. After the administration of single intraperitoneal doses of 25, 50, and 75 mg/kg of body weight, linezolid peak concentrations of 6.8, 12.7, and 18.1 μg/ml, respectively, were achieved in sterile cage fluid at ≈3 h. The linezolid concentration remained above the MIC of the test organism for 12 h with all doses. Antimicrobial treatments of animals with cage implant infections were given twice daily for 4 days. Linezolid alone at 25, 50, and 75 mg/kg reduced the planktonic bacteria in cage fluid during treatment by 1.2 to 1.7 log
10
CFU/ml; only linezolid at 75 mg/kg prevented bacterial regrowth 5 days after the end of treatment. Linezolid used in combination with rifampin (12.5 mg/kg) was more effective than linezolid used as monotherapy, reducing the planktonic bacteria by ≥3 log
10
CFU (
P
< 0.05). Efficacy in the eradication of cage-associated infection was achieved only when linezolid was combined with rifampin, with cure rates being between 50% and 60%, whereas the levofloxacin-rifampin combination demonstrated the highest cure rate (91%) against the strain tested. The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA.
Robust Antiviral Efficacy upon Administration of a Nucleoside Analog to Hepatitis C Virus-Infected Chimpanzees
Authors: Carroll Steven S. , Ludmerer Steven , Handt Larry , Koeplinger Kenneth , Zhang Nanyan Rena , Graham Donald , Davies Mary-Ellen , MacCoss Malcolm , Hazuda Daria , Olsen David B. 
Published: December 2008

ABSTRACT

Hepatitis C virus (HCV) infects an estimated 170 million individuals worldwide and is associated with an increased incidence of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Currently approved therapies to treat HCV infection consist of combinations of pegylated alpha interferon and ribavirin which result in a sustained viral response in 40 to 60% of patients. Efforts to develop improved therapies include the development of direct inhibitors of virally encoded enzymes such as the viral RNA-dependent RNA polymerase. A nucleoside analog, 2′-
C
-methyl-7-deaza-adenosine (MK-0608), has been shown to inhibit viral RNA replication in the subgenomic HCV genotype 1b replicon, with a 50% effective concentration (EC
50
) of 0.3 μM (EC
90
= 1.3 μM). To determine efficacy in vivo, MK-0608 was administered to HCV-infected chimpanzees, resulting in dose- and time-dependent decreases in plasma viral loads. In separate experiments, chimpanzees dosed for 7 days with MK-0608 at 0.2 and 2 mg per kg of body weight per day by intravenous administration experienced average reductions in viral load of 1.0 and >5 log
10
IU/ml, respectively. Two other HCV-infected chimpanzees received daily doses of 1 mg MK-0608 per kg via oral administration. After 37 days of oral dosing, one chimpanzee with a high starting viral load experienced a reduction in viral load of 4.6 log
10
, and the viral load in the other chimpanzee fell below the limit of quantification (LOQ) of the HCV TaqMan assay (20 IU/ml). Importantly, viral load remained below the LOQ throughout the duration of dosing and for at least 12 days after dosing ended. The results demonstrate a robust antiviral effect on the administration of MK-0608 to HCV-infected chimpanzees.
In Vitro Efficacy of ST246 against Smallpox and Monkeypox
Authors: Smith Scott K. , Olson Victoria A. , Karem Kevin L. , Jordan Robert , Hruby Dennis E. , Damon Inger K. 
Published: December 2008

ABSTRACT
Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of ≤0.067 μM against variola virus and <0.04 μM against monkeypox virus. In a dose-dependent manner, plaque size and comet tail formation were markedly reduced in the presence of the drug at low, noncytotoxic concentrations between 0.015 and 0.05 μM. Our in vitro phenotype data suggest that ST-246 inhibits variola and monkeypox viruses similarly by reducing the production and release of enveloped orthopoxvirus and support the development of ST-246 as an antiviral therapeutic compound for the treatment of severe systemic orthopoxvirus infections.
Virologic Failure in Therapy-Naïve Subjects on Aplaviroc plus Lopinavir-Ritonavir: Detection of Aplaviroc Resistance Requires Clonal Analysis of Envelope
Authors: Kitrinos Kathryn M. , Amrine-Madsen Heather , Irlbeck David M. , Word J. Michael , Demarest James F. 
Published: December 2008

ABSTRACT

The CCR100136 (EPIC) study evaluated the antiviral activity of the novel CCR5 entry inhibitor aplaviroc in combination with lopinavir-ritonavir in drug-naïve human immunodeficiency virus type 1-infected subjects. Although the trial was stopped prematurely due to idiosyncratic hepatotoxicity, 11 subjects met the protocol-defined virologic failure criteria. Clonal analyses of the viral envelope tropism, aplaviroc susceptibility, and
env
sequencing were performed on plasma at day 1 and at the time of virologic failure. Molecular evolutionary analyses were also performed. Treatment-emergent resistance to aplaviroc or lopinavir-ritonavir was not observed at the population level. However, aplaviroc resistance was detected prior to therapy at both the clonal and population levels in one subject with virologic failure and in six subjects in a minority (<50%) of clones at day 1 or at the time of virologic failure. Reduced aplaviroc susceptibility manifested as a 50% inhibitory concentration curve shift and/or a plateau. Sequence changes in the clones with aplaviroc resistance were unique to each subject and scattered across the envelope coding region. Clones at day 1 and at the time of virologic failure were not phylogenetically distinct. Two subjects with virologic failure had a population tropism change from CCR5- to dual/mixed-tropic during treatment. Virologic failure during a regimen of aplaviroc and lopinavir-ritonavir may be associated with aplaviroc resistance, only at the clonal level, and/or, infrequently, tropism changes.
The Emerging Human Pathogen
Photorhabdus asymbiotica
Is a Facultative Intracellular Bacterium and Induces Apoptosis of Macrophage-Like Cells
Authors: Costa S. C. P. , Girard P. A. , Brehélin M. , Zumbihl R. 
Published: December 2008

ABSTRACT

Photorhabdus
species are gram-negative entomopathogenic bacteria of the family
Enterobacteriaceae
. Among the different members of the genus, one species,
Photorhabdus asymbiotica
, is a pathogen of both insects and humans. The pathogenicity mechanisms of this bacterium are unknown. Here we show that
P. asymbiotica
is a facultative intracellular pathogen that is able to replicate inside human macrophage-like cells. Furthermore,
P. asymbiotica
was shown for the first time in an intracellular location after insect infection. We also demonstrated that among Australian and American clinical isolates, only the Australian strains were able to invade nonphagocytic human cells. In cell culture infection experiments, Australian clinical isolates as well as cell-free bacterial culture supernatant induced strong apoptosis of a macrophage cell line at 6 h postinfection. American isolates also induced cellular death, but much later than that induced by Australian ones. Mammalian cultured cells analyzed for key features of apoptosis displayed apoptotic nuclear morphology, activation of the initiator caspases 8 and 9 and the executioner caspases 3 and 7, and poly(ADP-ribose) polymerase proteolysis, suggesting activation of both the intrinsic and extrinsic apoptotic pathways.
Lactobacillus bulgaricus
Prevents Intestinal Epithelial Cell Injury Caused by
Enterobacter sakazakii
-Induced Nitric Oxide both In Vitro and in the Newborn Rat Model of Necrotizing Enterocolitis
Authors: Hunter Catherine J. , Williams Monica , Petrosyan Mikael , Guner Yigit , Mittal Rahul , Mock Dennis , Upperman Jeffrey S. , Ford Henri R. , Prasadarao Nemani V. 
Published: December 2008

ABSTRACT

Enterobacter sakazakii
is an emerging pathogen that has been associated with outbreaks of necrotizing enterocolitis (NEC) as well as infant sepsis and meningitis. Our previous studies demonstrated that
E. sakazakii
induces NEC in a newborn rat model by inducing enterocyte apoptosis. However, the mechanisms responsible for enterocyte apoptosis are not known. Here we demonstrate that
E. sakazakii
induces significant production of nitric oxide (NO) in rat intestinal epithelial cells (IEC-6) upon infection. The elevated production of NO, which is due to increased expression of inducible NO synthase, is responsible for apoptosis of IEC-6 cells. Notably, pretreatment of IEC-6 cells with
Lactobacillus bulgaricus
(ATCC 12278) attenuated the upregulation of NO production and thereby protected the cells from
E. sakazakii
-induced apoptosis. Furthermore, pretreatment with
L. bulgaricus
promoted the integrity of enterocytes both in vitro and in the infant rat model of NEC, even after challenge with
E. sakazakii
. Infection of IEC-6 cells with
E. sakazakii
upregulated several genes related to apoptosis, cytokine production, and various signaling pathways, as demonstrated by rat gene array analysis, and this upregulation was subdued by pretreatment with
L. bulgaricus
. In agreement with these data,
L. bulgaricus
pretreatment protected newborn rats infected with
E. sakazakii
from developing NEC, resulting in improved survival.