bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorothioate Di- and Trinucleotides as a Novel Class of Anti-Hepatitis B Virus Agents
Authors: Iyer Radhakrishnan P. , Jin Yi , Roland Arlene , Morrey John D. , Mounir Samir , Korba Brent 
Published: May 2004

ABSTRACT

Several nucleoside analogs are under clinical development for use against hepatitis B virus (HBV). Lamivudine (3TC), a nucleoside analog, and adefovir dipivoxil (ADV), an acyclonucleotide analog, are clinically approved. However, long-term treatment can induce viral resistance, and following the cessation of therapy, viral rebound is frequently observed. There continues to be a need for new antiviral agents with novel mechanisms of action. A library of more than 600 di- and trinucleotide compounds synthesized by parallel synthesis using a combinatorial strategy was screened for potential inhibitors of HBV replication using the chronically HBV-producing cell line 2.2.15. Through an iterative process of synthesis, lead optimization, and screening, three analogs were identified as potent inhibitors of HBV replication: dinucleotides ORI-7246 (drug concentration at which a 10-fold reduction of HBV DNA was observed [EC
90
], 1.4 μM) and ORI-9020 (EC
90
, 1.2 μM) and trinucleotide ORI-7170 (EC
90
, 7.2 μM). These analogs inhibited the replication of both strands of HBV DNA. No suppression of HBV protein synthesis or intracellular core particle formation by these analogs was observed. No inhibition of HBV DNA strand elongation by the analogs or their 5′-triphosphate versions was apparent in in vitro polymerase assays. Although the exact mechanism of action is not yet identified, present data are consistent with an inhibition of the HBV reverse transcriptase-directed priming step prior to elongation of the first viral DNA strand. In transient-transfection assays, these analogs inhibited the replication of 3TC-resistant HBV. Synergistic interactions in combination treatments between the analogs and either 3TC or ADV were observed. These compounds represent a novel class of anti-HBV molecules and warrant further investigation as potential therapeutic agents.
Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis
Authors: Tomaselli Florian , Maier Alfred , Matzi Veronika , Smolle-Jüttner Freyja Maria , Dittrich Peter 
Published: May 2004

ABSTRACT
Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 ± 10.9 mg/liter, and that in serum was 47.3 ± 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 ± 17.9 mg · h/liter) and serum (95.4 ± 46.6 mg · h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.
Effect of Erythromycin on Chronic Respiratory Infection Caused byPseudomonas aeruginosawith Biofilm Formation in an Experimental Murine Model
Authors: Nagata Towako , Mukae Hiroshi , Kadota Junichi , Hayashi Tomayoshi , Fujii Takeshi , Kuroki Misuzu , Shirai Ryo , Yanagihara Katsunori , Tomono Kazunori , Koji Takehiko , Kohno Shigeru 
Published: May 2004

ABSTRACTDiffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stagePseudomonas aeruginosainfection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratoryP. aeruginosainfection. ERY or saline was administered from day 80 after intubation with aP. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viableP. aeruginosaorganisms in the lungs (P< 0.05). The biofilm formed in situ byP. aeruginosaon the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction inP. aeruginosabiofilm formation.
Noninvasive Optical Imaging Method To Evaluate Postantibiotic Effects on Biofilm Infection In Vivo
Authors: Kadurugamuwa Jagath L. , Sin Lin V. , Yu Jun , Francis Kevin P. , Purchio Tony F. , Contag Pamela R. 
Published: May 2004

ABSTRACT

Eradication of
Staphylococcus aureus
biofilms after rifampin treatment was tested in a mouse model of device-related infection by using biophotonic imaging. Following treatment, the bioluminescent signals decreased to undetectable levels, irrespective of the age of the biofilm. After the final treatment, the signals rebounded in a time-dependent manner and reached those for the untreated mice. Readministration of rifampin was unsuccessful in eradicating reestablished infections, with the rifampin MICs for such bacteria being increased and with the bacteria having point mutations in the
rpoB
gene.
Salmonella
Gene
rma
(
ramA
) and Multiple-Drug-Resistant
Salmonella enterica
Serovar Typhimurium
Authors: van der Straaten Tahar , Janssen Riny , Mevius Dik J. , van Dissel Jaap T. 
Published: May 2004

ABSTRACT

MarA and its homologue, RamA, have been implicated in multidrug resistance (MDR).
RamA
overexpression in
Salmonella enterica
serovar Typhimurium and
Escherichia coli
conferred MDR independently of
marA
. Inactivation of
ramA
did not affect the antibiotic susceptibilities of wild-type
S. enterica
serovar Typhimurium or 15 unrelated clinical MDR isolates. Thus,
ramA
overexpression is not a common MDR mechanism in
Salmonella
.
Fitness Cost of SCC
mec
and Methicillin Resistance Levels in
Staphylococcus aureus
Authors: Ender Miriam , McCallum Nadine , Adhikari Rajan , Berger-Bächi Brigitte 
Published: May 2004

ABSTRACT

Transformation of a type I SCC
mec
element into
Staphylococcus aureus
yielded highly oxacillin-resistant transformants with a reduced growth rate. Faster-growing variants could again be selected at the cost of reduced resistance levels, demonstrating an inverse correlation between oxacillin resistance levels and growth rate.
In Vitro Effects of Albendazole Sulfoxide and Praziquantel against
Taenia solium
and
Taenia crassiceps
Cysts
Authors: Palomares Francisca , Palencia Guadalupe , Pérez Rodolfo , González-Esquivel Dinora , Castro Nelly , Cook Helgi Jung 
Published: May 2004

ABSTRACT

We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against
Taenia
cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts much slower and is less potent than PZQ.
High-Level Resistance to Ceftazidime Conferred by a Novel Enzyme, CTX-M-32, Derived from CTX-M-1 through a Single Asp240-Gly Substitution
Authors: Cartelle Monica , del Mar Tomas Maria , Molina Francisca , Moure Rita , Villanueva Rosa , Bou German 
Published: May 2004

ABSTRACT

A clinical strain of
Escherichia coli
isolated from pleural liquid with high levels of resistance to cefotaxime, ceftazidime, and aztreonam harbors a novel CTX-M gene (
bla
CTX-M-32
) whose amino acid sequence differs from that of CTX-M-1 by a single Asp240-Gly substitution. Moreover, by site-directed mutagenesis we demonstrated that this replacement is a key event in ceftazidime hydrolysis
Molecular Characterization of a Carbapenem-Hydrolyzing Class A β-Lactamase, SFC-1, from
Serratia fonticola
UTAD54
Authors: Henriques Isabel , Moura Alexandra , Alves Artur , Saavedra Maria José , Correia António 
Published: May 2004

ABSTRACT

An environmental isolate of
Serratia fonticola
resistant to carbapenems contains a gene encoding a class A β-lactamase with carbapenemase activity. The enzyme was designated SFC-1. The
bla
SFC-I
gene is contained in the chromosome of
S. fonticola
UTAD54 and is absent from other
S. fonticola
strains.
Potential New Anti-Human Immunodeficiency Virus Type 1 Compounds Depress Virus Replication in Cultured Human Macrophages
Authors: Ewart Gary D. , Nasr Najla , Naif Hassan , Cox Graeme B. , Cunningham Anthony L. , Gage Peter W. 
Published: May 2004

ABSTRACT

We report that the amiloride analogues 5-(
N
,
N
-hexamethylene)amiloride and 5-(
N
,
N
-dimethyl)amiloride inhibit, at micromolar concentrations, the replication of human immunodeficiency virus type 1 (HIV-1) in cultured human blood monocyte-derived macrophages. These compounds also inhibit the in vitro activities of the HIV-1 Vpu protein and might represent lead compounds for a new class of anti-HIV-1 drugs.
Effect of trail design and grooming on the incidence of injuries at alpine ski areas
Authors: Bergstrøm K A , Ekeland A 
Published: May 2004

Objectives:To identify the conditions at certain sites on slopes known as black spots for injury.Method:In the Hafjell and Voss alpine ski areas in Norway, 1410 skiing injuries were recorded from December 1990 through the 1996 season. In Hafjell, 183 of these injuries were plotted on an area map during the two first seasons. Similarly, in Voss, 214 injuries were plotted on an area map for two seasons. During the last three seasons in Hafjell, 835 ski injuries were related to 6712 snow grooming hours and 6 829 084 lift journeys.Results:The mean injury rate was 2.2 injuries per 1000 skier days, and the mean injury severity score (ISS) was 3.1. Accumulations of injuries at three sites (black spots) were recorded on the Hafjell area map. These injuries represented 40% of all injuries in the alpine area (p<0.05). Seven injury accumulation sites were recorded on the alpine area map of Voss, representing 22% of the total injuries (p>0.05). Grooming of the slopes was rated poor for the 49% of injuries that occurred at the sites of injury concentration and significantly different (27%) from injuries that occurred at random in Hafjell. The corresponding values in Voss were 50% and 25% respectively. Grooming hours appeared to be inversely proportional to the number of injuries:R =  −0.99 (p<0.02). The mean ISS declined significantly in Hafjell over the observation period (p<0.001).Conclusion:Inappropriate trail design and slope grooming seem to result in an accumulation of injuries at certain sites. Modification in construction and maintenance of the courses may reduce the number of injuries and mean ISS.
Role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation
Authors: Hayes S C , Davies P S , Parker T W , Bashford J , Green A 
Published: May 2004

Objectives:To evaluate the effect of peripheral blood stem cell transplantation on functional capacity, and to determine the role of a mixed type, moderate intensity exercise programme in the recovery of patients after intensive cancer treatment.Methods:Peak aerobic capacity and muscular strength (upper body, lower body, and handgrip strength) measures were assessed before (PI) and after (PII) transplant and after a 12 week intervention period (PIII). After PII, 12 patients aged 16–64 years were allotted in equal numbers to a control group or exercise intervention group.Results:Mean peak aerobic capacity and muscular strength were reduced after the transplant, with significant (p<0.05) decreases for upper body strength. No change was found in aerobic capacity and muscular strength between PII and PIII for the control group. In contrast, participation in the exercise programme led to significant improvements in peak aerobic capacity (p<0.05) and upper and lower body strength (p<0.01). In addition, values recorded after the three month intervention period were significantly higher than before treatment for peak aerobic capacity (litres/min (p<0.05) and ml/kg/min (p<0.01)) and lower body strength (p<0.01).Conclusion:Intensive treatment for cancer can adversely affect aerobic capacity and muscular strength. A mixed type, moderate intensity exercise programme can help patients to regain fitness and strength within three months. No exercise can exacerbate physical losses resulting from treatment.
Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study
Authors: Predel H G , Koll R , Pabst H , Dieter R , Gallacchi G , Giannetti B , Bulitta M , Heidecker J L , Mueller E A 
Published: May 2004

Objectives:To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries.Methods:This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.Results:The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2(95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group.Conclusions:A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries.
Effect of a Standardized Meal on the Bioavailability of a Single Oral Dose of Tibolone 2.5 mg in Healthy Postmenopausal Women
Authors: Timmer Cees J. , Huisman Johannes A. M. 
Published: May 2004

Study Objective. To assess the effect of food on absorption and pharmaco‐kinetic disposition of tibolone.Design. Open‐label, randomized, crossover study with a 1‐week washout period.Setting. Institut für Klinische Pharmakologie, Höhenkirchen‐Siegertsbrunn, Germany.Subjects. Twenty‐four healthy, early postmenopausal women.Intervention. Single doses of tibolone 2.5 mg were administered after subjects consumed a high‐fat meal or fasted.Measurements and Main Results. Plasma concentrations of tibolone and its three primary metabolites, Δ4‐tibolone, 3α‐hydroxytibolone, and 3β‐hydroxytibolone, were assayed by gas chromatography with mass spectrometry. Peak plasma concentration (Cmax), time to Cmax, area under the plasma concentration versus time curve from time zero to infinity (AUC0‐∞), and elimination half‐life were calculated, and food effects were evaluated. Plasma concentrations of tibolone and Δ4‐tibolone were too low to estimate AUC0‐∞ and half‐life. Absorption or formation of 3α‐hydroxytibolone and 3β‐hydroxytibolone was slower in fed participants than in fasting participants, but this was of no clinical relevance because of the long‐term nature of tibolone treatment. Meal consumption did not affect AUC0‐∞ or half‐life for 3α‐hydroxytibolone and 3β‐hydroxytibolone.Conclusion. Food consumption decreased and delayed Cmax but had no effect on the exposure of tibolone and its metabolites. Tibolone therefore can be administered irrespective of meal timing.
Effect of Milk Thistle on the Pharmacokinetics of Indinavir in Healthy Volunteers
Authors: Piscitelli Stephen C. , Formentini Elizabeth , Burstein Aaron H. , Alfaro Raul , Jagannatha Shyla , Falloon Judith 
Published: May 2004

Study Objective. To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition.Design. Prospective open‐label drug interaction study.Setting. Outpatient clinic.Subjects. Ten healthy volunteers.Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11‐day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction.Measurements and Main Results. Indinavir concentrations were measured by using a validated high‐performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour‐0 concentration, hour‐8 concentration (C8), time to reach Cmax, and area under the plasma concentration‐time curve over the 8‐hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%.Conclusion. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.
Effectiveness of Pretreatment in Decreasing Adverse Events Associated with Pamidronate in Children and Adolescents
Authors: Robinson Renee F. , Nahata Milap C. , Hayes John R. , Batisky Donald L. , Bates Carlton M. , Mahan John D. 
Published: May 2004

Study Objectives. To assess the effectiveness of pretreatment with ibuprofen or acetaminophen compared with no pretreatment in decreasing adverse events in children and adolescents receiving the first and second series of pamidronate therapy; and to compare the effectiveness of ibuprofen versus acetaminophen for prevention of adverse events associated with pamidronate infusion.Design. Retrospective case review.Setting. Children's hospital.Patients. Twenty‐seven children and adolescents aged 3–21 years receiving pamidronate therapy.Measurements and Main Results. Data for patient demographics, medical history, genetic history of disease, pamidronate infusion dosage, and concurrent drug therapy were collected. Adverse drug events secondary to pamidronate infusion and subsequent drug therapies received were documented. Data were categorized by presence or absence of pretreatment and analyzed by cross‐tabulation to determine whether the presence of adverse events differed between groups (no pretreatment, acetaminophen pretreatment, and ibuprofen pretreatment). Fewer adverse events were reported in patients receiving ibuprofen (17% of patients) versus acetaminophen (83%). Differences in presence of fever (χ2=10.5, p=0.005) and bone pain (χ2=7.3, p=0.027) among the three pretreatment groups were also statistically significant.Conclusion. Pretreatment with ibuprofen or acetaminophen appears to decrease the occurrence of adverse events from pamidronate therapy. However, adverse events seem less likely to occur with ibuprofen. Further study is necessary to determine the relationship between occurrence of adverse events, other possible treatment strategies, and patient adherence with pamidronate therapy.
Pharmacodynamic Effects of Zidovudine 600 mg Once/Day versus 300 mg Twice/Day in Therapy‐Naïve Patients Infected with Human Immunodeficiency Virus
Authors: Ruane Peter J. , Richmond Gary J. , DeJesus Edwin , Hill‐Zabala Christina E. , Danehower Susan C. , Liao Qiming , Johnson Judy , Shaefer Mark S. 
Published: May 2004

Study Objective. To compare the virologic activity of zidovudine monotherapy administered as 600 mg once/day versus 300 mg twice/day.Design. Phase II, randomized (1:1), open‐label study.Setting. Thirteen medical centers in the United States.Patients. Thirty‐two antiretroviral‐naïve patients infected with human immunodeficiency virus (HIV).Intervention. Patients were administered either zidovudine 600 mg every 24 hours (16 patients) or 300 mg every 12 hours (16 patients) for 13 days.Measurements and Main Results. Plasma HIV‐1 RNA concentration was measured daily. Study end points were between‐group differences in change from baseline of log10‐transformed HIV‐1 RNA and in rates of viral load decline measured by the slope of HIV‐1 RNA over time. At baseline, mean HIV‐1 RNA was similar in the once/day and twice/day groups (4.33 and 4.40 log10 copies/ml, respectively). At day 14, a trend toward lower mean reduction in HIV‐1 RNA from baseline was observed in the once/day group (−0.585, 95% confidence interval [CI] −0.728 to −0.442 log10 copies/ml) compared with the twice/day group (−0.849, 95% CI −1.067 to −0.630 log10 copies/ml, p=0.056). Viral load reduction also tended to be slower in the once/day group, as indicated by the smaller slope of viral load decline in the once/day group than in the twice/day group during days 1–14 (−0.045 vs −0.065 log10 copies/ml/day, p=0.065). Both zidovudine regimens were similarly well tolerated.Conclusion. Zidovudine 600 mg once/day has antiviral activity, although less pronounced and more slowly achieved than that seen with zidovudine 300 mg twice/day. No differences were observed between the two treatment groups with respect to safety profile or tolerability.
Model‐free recursive LQ controller design (learning LQ control)
Authors: Kawamura Yoshiaki , Nakano Masahiro , Yamamoto Hiroyuki 
Published: May 2004

AbstractA new data‐based iterative self‐optimizing approach to practical design (learning/adaptive process) of the infinite‐horizon LQ regulator is proposed. Optimality is given by a certain orthogonality condition of response signals, and the global convergence of feedback gain is proved for MIMO systems by an expansion of the Riccati equation. The design is applied to stabilizing control and steady state error‐less control of physical systems. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: Bis{[diacetyl‐bis(2,6‐isopropylphenylimine)]nickel(I)(µ‐chloro)}
Authors: Shao Qing , Sun Hongmei , Shen Qi , Zhang Yong 
Published: May 2004

AbstractThe first α‐diimine nickel(I) complex having a chloro bridge is reported. The centrosymmetric dinuclear structure of {[ArNC(Me)C(Me)NAr]NiCl}2[Ar2,6−C6H3(i‐Pr)2] features two chelating α‐diimine ligands and two bridged chlorine atoms, so that a distorted tetrahedral N2Cl2 coordination geometry for nickel results. Copyright © 2004 John Wiley & Sons, Ltd.