bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen sulfide acts as a mediator of inflammation inacute pancreatitis: in vitro studies using isolated mouse pancreatic acinar cells
Authors: Tamizhselvi Ramasamy , Moore Philip K. , Bhatia Madhav 
Published: May 2007

AbstractHydrogen sulphide (H2S) is synthesized from L‐cysteine via the action of cystathionine‐γ‐lyase (CSE) and cystathionine‐β‐synthase (CBS). We have earlier shown that H2S acts as a mediator of inflammation. However the mechanism remains unclear. In this study, we investigated the presence of H2S and the expression of H2S synthesizing enzymes, CSE and CBS, in isolated mouse pancreatic acini. Pancreatic acinar cells from mice were incubated with or without caerulein (10−7 M for 30 and 60 min). Caerulein increased the levels of H2S and CSE mRNA expression while CBS mRNA expression was decreased. In addition, cells pre‐treated with DL‐propargylglycine (PAG, 3 mM), a CSE inhibitor, reduced the formation of H2S in caerulein treated cells, suggesting that CSE may be the main enzyme involved in H2S formation in mouse acinar cells. Furthermore, substance P (SP) concentration in the acini and expression of SP gene (preprotachykinin‐A, PPT‐A) and neurokinin‐1 receptor (NK‐1R), the primary receptor for SP, are increased in secretagogue caerulein‐treated acinar cells. Inhibition of endogenous production of H2S by PAG significantly suppressed SP concentration, PPT‐A expression and NK1‐R expression in the acini. To determine whether H2S itself provoked inflammation in acinar cells, the cells were treated with H2S donor drug, sodium hydrosulphide (NaHS), (10, 50 and 100 μM), that resulted in a significant increase in SP concentration and expression of PPT‐A and NK1‐R in acinar cells. These results suggest that the pro‐inflammatory effect of H2S may be mediated by SP‐NK‐1R related pathway in mouse pancreatic acinar cells.
The effect of Cyclosporine A on cardiomyocytes differentiation
Authors: Paslaru Liliana , Davidson Sean , Popescu Irinel , Morange Michel 
Published: May 2007

AbstractCyclosporine A (CsA) is a powerful immunosuppressive drug which significantly improved the success of organ transplantation; however, the major limiting factors for the drug's clinical use are its long and short term adverse effects. The present study was conducted to examine, in a dose‐dependent manner, in a model of cardiogenesis, the effect of CsA on cardiomyocytes differentiation.
Adaptive Underrelaxation of Picard Iterations in Ground Water Models
Authors: Durbin Timothy , Delemos David 
Published: May 2007

AbstractThis methods note examines the use of adaptive underrelaxation of Picard iterations to accelerate the solution convergence for nonlinear ground water flow problems. Ground water problems are nonlinear when drains, phreatophytes, stream aquifer, and similar features are simulated. Typically, simple Picard iterations are used to address such nonlinear problems. Nevertheless, the convergence rate can be slow, or convergence cannot be obtained. However, convergence often can be accelerated using Picard iterations with adaptive underrelaxation, and convergence often can be obtained where it otherwise would not occur.
A Hybrid Artificial Neural Network‐Numerical Model for Ground Water Problems
Authors: Szidarovszky Ferenc , Coppola Emery A. , Long Jingjie , Hall Anthony D. , Poulton Mary M. 
Published: May 2007

AbstractNumerical models constitute the most advanced physical‐based methods for modeling complex ground water systems. Spatial and/or temporal variability of aquifer parameters, boundary conditions, and initial conditions (for transient simulations) can be assigned across the numerical model domain. While this constitutes a powerful modeling advantage, it also presents the formidable challenge of overcoming parameter uncertainty, which, to date, has not been satisfactorily resolved, inevitably producing model prediction errors. In previous research, artificial neural networks (ANNs), developed with more accessible field data, have achieved excellent predictive accuracy over discrete stress periods at site‐specific field locations in complex ground water systems. In an effort to combine the relative advantages of numerical models and ANNs, a new modeling paradigm is presented. The ANN models generate accurate predictions for a limited number of field locations. Appending them to a numerical model produces an overdetermined system of equations, which can be solved using a variety of mathematical techniques, potentially yielding more accurate numerical predictions. Mathematical theory and a simple two‐dimensional example are presented to overview relevant mathematical and modeling issues. Two of the three methods for solving the overdetermined system achieved an overall improvement in numerical model accuracy for various levels of synthetic ANN errors using relatively few constrained head values (i.e., cells), which, while demonstrating promise, requires further research. This hybrid approach is not limited to ANN technology; it can be used with other approaches for improving numerical model predictions, such as regression or support vector machines (SVMs).
In Vitro Resistance Selection and In Vivo Efficacy of Morpholino Oligomers against West Nile Virus
Authors: Deas Tia S. , Bennett Corey J. , Jones Susan A. , Tilgner Mark , Ren Ping , Behr Melissa J. , Stein David A. , Iversen Patrick L. , Kramer Laura D. , Bernard Kristen A. , Shi Pei-Yong 
Published: May 2007

ABSTRACT
We characterize in vitro resistance to and demonstrate the in vivo efficacy of two antisense phosphorodiamidate morpholino oligomers (PMOs) against West Nile virus (WNV). Both PMOs were conjugated with an Arg-rich peptide. One peptide-conjugated PMO (PPMO) binds to the 5′ terminus of the viral genome (5′-end PPMO); the other targets an essential 3′ RNA element required for genome cyclization (3′ conserved sequence I [3′ CSI] PPMO). The 3′ CSI PPMO displayed a broad spectrum of antiflavivirus activity, suppressing WNV, Japanese encephalitis virus, and St. Louis encephalitis virus, as demonstrated by reductions in viral titers of 3 to 5 logs in cell cultures, likely due to the absolute conservation of the 3′ CSI PPMO-targeted sequences among these viruses. The selection and sequencing of PPMO-resistant WNV showed that the 5′-end-PPMO-resistant viruses contained two to three mismatches within the PPMO-binding site whereas the 3′ CSI PPMO-resistant viruses accumulated mutations outside the PPMO-targeted region. The mutagenesis of a WNV infectious clone demonstrated that the mismatches within the PPMO-binding site were responsible for the 5′-end PPMO resistance. In contrast, a U insertion or a G deletion located within the 3′-terminal stem-loop of the viral genome was the determinant of the 3′ CSI PPMO resistance. In a mouse model, both the 5′-end and 3′ CSI PPMOs (administered at 100 or 200 μg/day) partially protected mice from WNV disease, with minimal to no PPMO-mediated toxicity. A higher treatment dose (300 μg/day) caused toxicity. Unconjugated PMOs (3 mg/day) showed neither efficacy nor toxicity, suggesting the importance of the peptide conjugate for efficacy. The results suggest that a modification of the peptide conjugate composition to reduce its toxicity yet maintain its ability to effectively deliver PMO into cells may improve PMO-mediated therapy.
Steady-State Disposition of the Nonpeptidic Protease Inhibitor Tipranavir when Coadministered with Ritonavir
Authors: Chen Linzhi , Sabo John P. , Philip Elsy , Mao Yanping , Norris Stephen H. , MacGregor Thomas R. , Wruck Jan M. , Garfinkel Sandra , Castles Mark , Brinkman Amy , Valdez Hernan 
Published: May 2007

ABSTRACT

The pharmacokinetic and metabolite profiles of the antiretroviral agent tipranavir (TPV), administered with ritonavir (RTV), in nine healthy male volunteers were characterized. Subjects received 500-mg TPV capsules with 200-mg RTV capsules twice daily for 6 days. They then received a single oral dose of 551 mg of TPV containing 90 μCi of [
14
C]TPV with 200 mg of RTV on day 7, followed by twice-daily doses of unlabeled 500-mg TPV with 200 mg of RTV for up to 20 days. Blood, urine, and feces were collected for mass balance and metabolite profiling. Metabolite profiling and identification was performed using a flow scintillation analyzer in conjunction with liquid chromatography-tandem mass spectrometry. The median recovery of radioactivity was 87.1%, with 82.3% of the total recovered radioactivity excreted in the feces and less than 5% recovered from urine. Most radioactivity was excreted within 24 to 96 h after the dose of [
14
C]TPV. Radioactivity in blood was associated primarily with plasma rather than red blood cells. Unchanged TPV accounted for 98.4 to 99.7% of plasma radioactivity. Similarly, the most common form of radioactivity excreted in feces was unchanged TPV, accounting for a mean of 79.9% of fecal radioactivity. The most abundant metabolite in feces was a hydroxyl metabolite, H-1, which accounted for 4.9% of fecal radioactivity. TPV glucuronide metabolite H-3 was the most abundant of the drug-related components in urine, corresponding to 11% of urine radioactivity. In conclusion, after the coadministration of TPV and RTV, unchanged TPV represented the primary form of circulating and excreted TPV and the primary extraction route was via the feces.
Amiodarone and Bepridil Inhibit Anthrax Toxin Entry into Host Cells
Authors: Sanchez Ana M. , Thomas Diane , Gillespie Eugene J. , Damoiseaux Robert , Rogers Joseph , Saxe Jonathan P. , Huang Jing , Manchester Marianne , Bradley Kenneth A. 
Published: May 2007

ABSTRACT

Anthrax lethal toxin is one of the fundamental components believed to be responsible for the virulence of
Bacillus anthracis
. In order to find novel compounds with anti-lethal toxin properties, we used a cell-based assay to screen a collection of approximately 500 small molecules. Nineteen compounds that blocked lethal toxin-mediated killing of RAW 264.7 macrophages were identified, and we report here on the characterization of the two most potent antitoxic compounds, amiodarone and bepridil. These drugs are used to treat cardiac arrhythmia or angina in humans at doses similar to those that provide protection against lethal toxin in vitro. Our results support a model whereby the antitoxic properties of both drugs result from their ability to block endosomal acidification, thereby blocking toxin entry. Amiodarone was tested in vivo and found to significantly increase survival of lethal toxin-challenged Fischer rats.
Efficacy of Telavancin in the Treatment of Experimental Endocarditis Due to Glycopeptide-Intermediate
Staphylococcus aureus
Authors: Miró José M. , García-de-la-Mària Cristina , Armero Yolanda , de-Lazzari Elisa , Soy Dolors , Moreno Asunción , del Rio Ana , Almela Manel , Mestres Carlos A. , Gatell José M. , Jiménez-de-Anta María-Teresa , Marco Francesc 
Published: May 2007

ABSTRACT

The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate
Staphylococcus aureus
: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 μg/ml and 6 μg/ml, respectively, for telavancin and 46 μg/ml and 6 μg/ml, respectively, for vancomycin. In glycopeptide-intermediate
S. aureus
ATCC 700788, telavancin sterilized 6 of 16 vegetations (37%), whereas vancomycin sterilized 4 of 20 (20%) (
P
= 0.29) compared with 0 of 17 in the control group. In HIP 5836 experiments, telavancin and vancomycin sterilized 5 of 16 (31%) and 1 of 15 (7%) vegetations (
P
= 0.17), respectively, compared with none in the control group. Telavancin reduced vegetation titers by 2.0 and 2.3 logs greater than vancomycin for the ATCC 700788 (4.6 [2.0 to 5.8] versus 6.6 [2.0 to 6.9] log CFU/g vegetation;
P
= 0.05) and HIP 5836 (4.4 [2.0 to 7.4] versus 6.7 [4.5 to 8.7] log CFU/g vegetation;
P
= 0.09) strains, respectively; these differences did not reach statistical significance. All isolates from vegetations remained susceptible to telavancin after therapy. The results suggest that telavancin may be an effective treatment for endocarditis caused by glycopeptide-intermediate
S. aureus
.
Transcriptional Response of
Candida parapsilosis
following Exposure to Farnesol
Authors: Rossignol Tristan , Logue Mary E. , Reynolds Kieran , Grenon Muriel , Lowndes Noel F. , Butler Geraldine 
Published: May 2007

ABSTRACT

In
Candida albicans
, the quorum-sensing molecule farnesol inhibits the transition from yeast to hyphae but has no effect on cellular growth. We show that the addition of exogenous farnesol to cultures of
Candida parapsilosis
causes the cells to arrest, but not at a specific stage in the cell cycle. The cells are not susceptible to additional farnesol. However, the cells do eventually recover from arrest. Unlike in
C. albicans
, in
C. parapsilosis
sterols are localized to the tips of budding cells, and this polarization is disrupted by the addition of farnesol. We used the results of a genome sequence survey to design and manufacture partial genomic microarrays that were applied to determining the transcriptional response of
C. parapsilosis
to the presence of exogenous farnesol. In both
C. albicans
and
C. parapsilosis
, exposure to farnesol results in increased expression of the oxidoreductases
GRP2
and
ADH7
and altered expression of genes involved in sterol metabolism. There is no effect on expression of
C. parapsilosis
orthologs of genes involved in hyphal growth in
C. albicans.
Farnesol therefore differs significantly in its effects on
C. parapsilosis
and
C. albicans
.
Systematic Comparison of the Population Pharmacokinetics and Pharmacodynamics of Piperacillin in Cystic Fibrosis Patients and Healthy Volunteers
Authors: Bulitta J. B. , Duffull S. B. , Kinzig-Schippers M. , Holzgrabe U. , Stephan U. , Drusano G. L. , Sörgel F. 
Published: May 2007

ABSTRACTRespiratory tract infections cause 90% of premature mortality in patients with cystic fibrosis (CF). Treatment ofPseudomonas aeruginosainfection is often very problematic. Piperacillin-tazobactam has good activity againstP. aeruginosa, but its pharmacokinetics (PK) in CF patients has not been compared to the PK in healthy volunteers in a controlled clinical study. Therefore, we compared the population PK and pharmacodynamics (PD) of piperacillin between CF patients and healthy volunteers. We studied 8 adult (median age, 20 years) CF patients (average total body weight [WT], 43.1 ± 7.8 kg) and 26 healthy volunteers (WT, 71.1 ± 11.8 kg) who each received 4 g piperacillin as a 5-min intravenous infusion. We determined piperacillin levels by high-performance liquid chromatography, and we used NONMEM for population PK and Monte Carlo simulation. We used a target time of nonprotein-bound concentration above the MIC of 50%, which represents near-maximal bacterial killing. Unscaled total clearance was 25% lower, and the volume of distribution was 31% lower in CF patients. Allometric scaling by lean body mass reduced the unexplained (random) between-subject variability in clearance by 26% compared to the variability of linear scaling by WT. A standard dosage regimen of 3 g/70 kg body WT every 4 h as a 30-min infusion (daily dose, 18 g) achieved a robust (≥90%) probability-of-target attainment (PTA) for MICs of ≤12 mg/liter in CF patients and ≤16 mg/liter in healthy volunteers. Alternative modes of administration allowed a marked dose reduction to 9 g daily. Prolonged (4-h) infusions of 3 g/70 kg WT every 8 h and continuous infusion (daily dose, 9 g), achieved a robust PTA for MICs of ≤16 mg/liter in both groups. Piperacillin achieved PTA expectation values of 64% and 89% againstP. aeruginosainfection in CF patients, based on susceptibility data from two German CF clinics.
Babesial Vector Tick Defensin againstBabesiasp. Parasites
Authors: Tsuji Naotoshi , Battsetseg Badgar , Boldbaatar Damdinsuren , Miyoshi Takeharu , Xuan Xuenan , Oliver James H. , Fujisaki Kozo 
Published: May 2007

ABSTRACTAntimicrobial peptides are major components of host innate immunity, a well-conserved, evolutionarily ancient defensive mechanism. Infectious disease-bearing vector ticks are thought to possess specific defense molecules against the transmitted pathogens that have been acquired during their evolution. We found in the tickHaemaphysalis longicornisa novel parasiticidal peptide named longicin that may have evolved from a common ancestral peptide resembling spider and scorpion toxins.H. longicornisis the primary vector forBabesiasp. parasites in Japan. Longicin also displayed bactericidal and fungicidal properties that resemble those of defensin homologues from invertebrates and vertebrates. Longicin showed a remarkable ability to inhibit the proliferation of merozoites, an erythrocyte blood stage of equineBabesia equi, by killing the parasites. Longicin was localized at the surface of theBabesiasp. parasites, as demonstrated by confocal microscopic analysis. In an in vivo experiment, longicin induced significant reduction of parasitemia in animals infected with the zoonotic and murineB. microti. Moreover, RNA interference data demonstrated that endogenous longicin is able to directly kill the canineB. gibsoni, thus indicating that it may play a role in regulating the vectorial capacity in the vector tickH. longicornis. Theoretically, longicin may serve as a model for the development of chemotherapeutic compounds against tick-borne disease organisms.
The prevalence of syndrome Z (the interaction of obstructive sleep apnoea with the metabolic syndrome) in a teaching hospital in Singapore
Authors: Venkateswaran Sridhar , Shankar Praveen 
Published: May 2007

Abstract

Background
Syndrome Z describes the interaction of obstructive sleep apnoea (OSA) with the metabolic syndrome.

Purpose of study
A pilot study to determine the prevalence of syndrome Z in a teaching hospital in Singapore.

Methods
Patients (age ⩾18 years) recruited for this prospective study had to satisfy three of the following five inclusion criteria: fasting glucose &gt;6.1 mmol/l, blood pressure ⩾130/85 mm Hg, HDL cholesterol &lt;1.04 mmol/l in men and &lt;1.2 mmol/l in women, triglycerides ⩾1.7 mmol/l, and a waist circumference &gt;102 cm in men and &gt;88 cm in women. All subjects underwent standard overnight polysomnography. Overnight fasting glucose and lipid levels were measured and baseline anthropometric data recorded. All sleep studies were scored and reported by a sleep physician. OSA was deemed to be present if the respiratory disturbance index (RDI) was ⩾5, with mild, moderate and severe categories classified according to the Chicago criteria.

Results
There were 24 patients (19 males and five females) of whom 10 were Chinese, eight Malay and five of Indian origin, with one other. Mean age was 48±13.5 years, mean body mass index was 34.9±6.1 kg/m2 and mean waist circumference was 111.3±15.7 cm. 23 (95.8%) of the patients had OSA with a mean RDI of 39.6±22.4 events/h with 15 patients (62.5%) in the severe category. The five patients who fulfilled all five criteria for diagnosis of the metabolic syndrome had severe OSA.

Conclusion
The prevalence of OSA in our studied population exhibiting the metabolic syndrome is very high. Therefore, a polysomnogram should always be considered for this subset of patients.
Comparison of P-POSSUM and O-POSSUM in predicting mortality after oesophagogastric resections
Authors: Nagabhushan J S , Srinath S , Weir F , Angerson W J , Sugden B A , Morran C G 
Published: May 2007

Abstract

Background
P-POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and morbidity) predicts mortality and morbidity in general surgical patients providing an adjunct to surgical audit. O-POSSUM was designed specifically to predict mortality and morbidity in patients undergoing oesophagogastric surgery.

Aim
To compare P-POSSUM and O-POSSUM in predicting surgical mortality in patients undergoing elective oesophagogastric cancer resections.

Methods
Elective oesophagogastric cancer resections in a district general hospital from 1990 to 2002 were scored by P-POSSUM and O-POSSUM methods. Observed mortality rates were compared to predicted mortality rates in six risk groups for each model using the Hosmer–Lemeshow goodness-of-fit test. The power to discriminate between patients who died and those who survived was assessed using the area under the receiver–operator characteristic (ROC) curve.

Results
313 patients underwent oesophagogastric resections. 32 died within 30 days (10.2%). P-POSSUM predicted 36 deaths (χ2 = 15.19, df = 6, p = 0.019, Hosmer–Lemeshow goodness-of-fit test), giving a standardised mortality ratio (SMR) of 0.89. O-POSSUM predicted 49 deaths (χ2 = 16.51, df = 6, p = 0.011), giving an SMR of 0.65. The area under the ROC curve was 0.68 (95% confidence interval 0.59 to 0.76) for P-POSSUM and 0.61 (95% confidence interval 0.50 to 0.72) for O-POSSUM.

Conclusion
Neither model accurately predicted the risk of postoperative death. P-POSSUM provided a better fit to observed results than O-POSSUM, which overpredicted total mortality. P-POSSUM also had superior discriminatory power.
The role of the Intra-aortic balloon pump in supporting children with acute cardiac failure
Authors: Paul Collison Sathiakar , Singh Dagar Kulbhusan 
Published: May 2007

Abstract
Acute heart failure occurs in children following the operative correction of a congenital anomaly, as an acute change in a child with a congenital anomaly, or in a structurally normal heart with acute myocarditis. Acute heart failure in children justifies aggressive treatment because of the high potential for complete recovery. The options for providing mechanical support to the failing heart in a child include extracorporeal membrane oxygenation, left ventricular assist devices and the use of the intra-aortic balloon pump (IABP). The principles of intra-aortic balloon pump usage are described, and the literature regarding the indications and outcome of its use in children is reviewed.