bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Vardenafil Administration Improves Bladder Oxygenation in Spontaneously Hypertensive Rats
Authors: Morelli Annamaria , Filippi Sandra , Comeglio Paolo , Sarchielli Erica , Chavalmane Aravinda K. , Vignozzi Linda , Fibbi Benedetta , Silvestrini Enrico , Sandner Peter , Gacci Mauro , Carini Marco , Vannelli Gabriella B. , Maggi Mario 
Published: November 2009

ABSTRACT

Introduction
In human bladder, phosphodiesterase type 5 (PDE5) is present not only in the muscular wall but also in the vascular beds, suggesting a role for PDE5 inhibitors in favoring bladder blood flow and tissue oxygenation.

Aim
To investigate whether acute administration of vardenafil could affect bladder oxygenation in spontaneously hypertensive rats (SHR), an animal model of naturally occurring overactive bladder.

Main Outcome Measures
The effect of vardenafil on hypoxia-induced alterations was studied in vivo in SHR by acute dosing (10 mg/kg, 90 minutes before sacrifice) and in vitro in human bladder smooth muscle cells (hBCs).

Methods
Bladder oxygenation was detected using the hypoxyprobe immunostaining. The expression of some hypoxia markers (vascular endothelial growth factor [VEGF] and endothelin-1 type B [ETB] receptor) was also evaluated by immunohistochemistry and Western blot. Gene expression in hBC was quantified by real-time reverse transcription-polymerase chain reaction.

Results
Rat bladder PDE5 immunopositivity was detected in the muscular wall and in the endothelial and smooth muscle cells of blood vessels. In SHR bladder, a significant increase of hypoxic cells, VEGF, and ETB expression was observed when compared with their normotensive counterpart Wistar Kyoto rats (WKY). Vardenafil treatment dramatically decreased hypoxyprobe staining, as well as VEGF and ETB expression in SHR bladder up to WKY level. Accordingly, in SHR bladder, vardenafil administration significantly blunted relaxation induced by the selective ETB agonist IRL-1620. In hBCs, experimental hypoxia significantly induced gene expression of hypoxia markers (carbonic anhydrase IX and VEGF), which was not changed by simultaneous treatment with vardenafil. Conversely, the hypoxia-related induction of smooth muscle-specific genes (αSMA, SM22α, and desmin) was significantly reduced by vardenafil.

Conclusions
SHR showed bladder hypoxia which was significantly reduced by acute vardenafil treatment. Thus, besides relaxing muscular wall, PDE5 inhibition may positively affect urinary vesicle blood perfusion.
Brief Review on Methods of Estimation of the Location of a Fresh Water–Salt Water Interface with Hydraulic Heads or Pressures in Coastal Zones
Authors: Xun Zhou , Ying Wang 
Published: November 2009

AbstractMethods of estimation of the location of a sharp fresh water–salt water interface with hydraulic heads or pressures are relatively simple and are widely used. Progress has been made in the recent decade toward the mathematical relations describing the position of the sharp interface using hydraulic heads or pressures in coastal zones. This paper reviews several methods for estimation of the location of fresh water–salt water interface in coastal aquifers, including the classical Ghyben–Herzberg relation. The location of the fresh water–salt water interface in a coastal homogeneous, isotropic unconfined aquifer can be estimated based on piezometric heads at two points in the same vertical line tapping, respectively, the salt water zone (including the interface) and the fresh water zone (from the water table to the interface) when the groundwater flow system is in a steady state and satisfies the Dupuit assumption. If pressures are measured at two points in the fresh water and salt water zones in the same vertical line in the coastal aquifer under the same assumption, then the position of the interface can still be estimated with the pressure data. If the Dupuit assumption is not met in coastal aquifers and the vertical fresh water head gradients can be approximated with a straight line, the position of the interface can roughly be estimated by using the water level data in a partially penetrating well during drilling of the well.
New developments in incretin‐based therapies: The current state of the field
Authors: Robertson Carolyn 
Published: November 2009

AbstractPurpose: To update readers on developments in incretin therapies since the previous JAANP supplement in 2007; specifically, to describe clinical data for currently available incretin‐based therapies as well as those under consideration by regulatory agencies.Data source: Medline search for peer‐reviewed publications.Conclusions: Incretin‐based therapies have pharmacologic properties that avoid some key limitations of previous treatments, such as hypoglycemia and weight gain. Certain agents also lower blood pressure and have the potential to reduce cardiovascular risk. The insulin‐secreting action of incretin‐based therapies only occurs under hyperglycemic conditions, thus minimizing the risk of hypoglycemia, unless combined with a sulfonylurea. The DPP‐4 inhibitors are orally administered and demonstrate modest A1c reductions (0.6%–0.8%); the best results occur when combined with metformin. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists liraglutide and exenatide have shown greater A1c reductions (typically ≥ 1.1% and as high as 1.7%), and these agents have beneficial ancillary effects, including weight and systolic blood pressure reduction. Both DPP‐4 inhibitors and GLP‐1 receptor agonists have shown the ability to improve pancreatic beta‐cell function in early studies.Implications for practice: Data are provided on the efficacy and tolerability of approved incretin therapies, and on treatments currently in regulatory review, in order to inform readers and guide their practice.
CREATIVE IRON MANAGEMENT—A PRACTICAL GUIDE
Authors: Jenkins Karen 
Published: November 2009

SUMMARYThe use of intravenous (IV) iron is now part of the every day management of anaemia in people with Chronic Kidney Disease (CKD). The increase in the number of referrals to renal services since the introduction of estimated glomerular filtration rate (eGFR) reporting in 2006 in England means that people with CKD are being identified earlier and consequently, complications such as anaemia are being highlighted sooner. The prevalence of anaemia of CKD has been estimated in a population study of stage 3–5 CKD as 4.5% (John et al. 2004). People with stage 3 CKD and diabetes have a 22% incidence of anaemia that is much greater than the incidence of 7.9% in those without diabetes (El Achkar et al. 2005). The increase in numbers requiring anaemia management is having an impact on resources and service provision, in particular the treatment of iron deficiency with IV iron. A need to be creative and investigate alternative ways of using resources and providing services in different settings was identified by the multiprofessional members of the Anaemia Nurse Specialist Association (ANSA) and the CKD forum (a project group of the British Renal Society). The outcome has been the production of a practical guide for healthcare professionals to assist with the development of IV iron services in a nonacute hospital setting. The guide was launched at the annual ANSA conference (April 2009) and British Renal Society conference (June 2009).
IRON THERAPY IN CHRONIC KIDNEY DISEASE: CURRENT CONTROVERSIES
Authors: Kovesdy Csaba P , Kalantar‐Zadeh Kamyar 
Published: November 2009

SUMMARYAnaemia in chronic kidney disease (CKD) is a complex disease that requires an integrated approach to incorporate both diagnostic and therapeutic interventions and to address the different facets of its aetiology and pathophysiology. The advent of erythropoiesis stimulating agents (ESA) has revolutionised the therapy of anaemia of CKD, and has resulted in a significant decline in the need for blood transfusions in CKD patients. The routine application of ESA has also led to the need for concomitant iron supplementation. ESA and iron therapy now form the cornerstone of anaemia management in CKD. Intravenous iron administration is effective with acceptable safety, and may improve ESA responsiveness. However, less is known about the long‐term safety of iron supplementation in CKD patients. Whereas maintenance (weekly to monthly) intravenous iron has been routinely used in maintenance dialysis patients, iron replacement in patients with non‐dialysis‐dependent CKD is less well studied, in spite of the much larger number of patients affected. This review discusses iron supplementation in CKD with an emphasis toward controversial issues that continue to pose dilemmas in clinical practice. Concerns related to both the optimal amount of iron supplementation and to the safety of various agents available in clinical practice are presented.
EVOLUTION OF IV IRON COMPOUNDS OVER THE LAST CENTURY
Authors: Macdougall Iain C 
Published: November 2009

SUMMARYAdministration of intravenous (IV) iron has become pivotal in the management of anaemia in patients with chronic kidney disease (CKD). Since parenteral iron was first introduced for human use in the 1930s, things have come a long way. Seventy years ago, iron was toxic, administered as an iron oxyhydroxide complex. This problem was circumvented with the introduction of compounds containing iron in a core surrounded by a carbohydrate shell. The carbohydrate shell consists of molecules such as dextran, sucrose, dextrin or gluconate. The first dextran‐containing IV iron preparations carried a small risk of anaphylaxis, but the more recently introduced low molecular weight iron dextran preparation has significantly less risk of this. Iron reactions occur with all IV iron preparations, but are generally not thought to be immune based. Recently, newer IV iron preparations have appeared in the market, including Ferumoxytol (Feraheme®) and ferric carboxymaltose (Ferinject®). These latest IV iron preparations do not contain a requirement for a test dose, and a much higher dose of iron can be delivered as a single administration. Thus, giving supplemental iron to man has come a long way since 1930s; we are now in an era when we are able to administer higher doses of iron with acceptable safety and without significant adverse effects. However, the long‐term safety of the newer IV iron preparations is not yet established.
AN EVIDENCE‐BASED APPROACH TO ANAEMIA MANAGEMENT IN PREDIALYSIS CHRONIC KIDNEY DISEASE
Authors: Pugh‐Clarke Karen , Cooper Liz , Turner June , Fermin Jenny 
Published: November 2009

SUMMARYThe use of Evidence‐based practice (EBP) is a decision‐making process, which integrates the best available research, clinician expertise, and client characteristics, integrating quality patient care in terms of clinical outcomes and cost‐effectiveness. This paper describes the application of EBP to an outpatient intravenous (IV) iron clinic for patients with predialysis chronic kidney disease (CKD).There has been an increasing focus on managing anaemia in patients with predialysis CKD. Along with the use of erythropoiesis stimulating agents, there has been an emerging interest in the use of IV iron preparations to treat anaemia in this patient population. Using EBP, we introduced a single dose preparation Ferinject® to replace our original IV iron protocol using Venofer®. As a test dose of Ferinject® is not required, it is extremely appropriate for use in busy nurse‐led IV iron clinics.Based upon the evidence generated from our initial trial of using Ferinject®, and our clinical experience of using this preparation, we have now converted our IV iron protocol to Ferinject®. Although the evaluation of Ferinject® in our predialysis population is ongoing, we are continuing to observe the benefits of using this preparation, both in terms of patient outcome and cost‐effectiveness. We consider that the use of Ferinject® has reduced waiting time and waiting list pressure, and also reduced material and hospital transport costs, which are significant due to the large geographical area covered by our CKD service.
Detection of antinuclear antibodies by the Inno‐Lia ANA update test in canine systemic rheumatic disease
Authors: Hansson‐Hamlin Helene , Rönnelid Johan 
Published: November 2009

Background: Certain systemic autoimmune diseases in dogs are characterized by high titers of circulating antinuclear antibodies (ANA), which can be demonstrated by indirect immunofluorescence (IIF). In an earlier study of IIF‐ANA–positive dogs, the Ouchterlony double immunodiffusion (DID) test was used to identify specific autoantibodies. The DID test has largely been replaced with line blot tests in human diagnostic settings.Objective: The objective of this study was to investigate whether the line blot assay Inno‐Lia ANA update test is a useful tool in demonstrating ANA specificities in canine patients with previously diagnosed IIF‐ANA–positive rheumatic disorders.Methods: Serum samples from 3 clinically healthy control dogs and 20 canine patients with clinical signs of systemic rheumatic disease and documented positive results for IIF‐ANA and DID tests were included in the study. The Inno‐Lia ANA update assay was performed with an anti‐canine detection antibody.Results: Six serum samples that had DID positivity with anti‐spliceosomal small nuclear ribonucleoproteins (snRNP) reactivity showed reactivity to multiple snRNP proteins in the Inno‐Lia test. Samples from 2 dogs that had other types of DID positivity also had clear SmB reactivity and 1 had weak reactivity to RNP‐70K. The other serum samples, including controls, were negative.Conclusions: Using the Inno‐Lia ANA update test, multiple snRNP specificities were demonstrated in some canine patients with autoimmune rheumatic disorders. Other canine autoantibodies may exist that are not detected by this test. Further studies are necessary to characterize the target antigen(s) of these remaining autoantibodies in canine sera.
Molecular and Biochemical Characterization of the Natural Chromosome-Encoded Class A β-Lactamase from
Pseudomonas luteola
Authors: Doublet Benoît , Robin Frédéric , Casin Isabelle , Fabre Laëtitia , Le Fleche Anne , Bonnet Richard , Weill François-Xavier 
Published: November 2009

ABSTRACT

Pseudomonas luteola
(formerly classified as CDC group Ve-1 and named
Chryseomonas luteola
) is an unusual pathogen implicated in rare but serious infections in humans. A novel β-lactamase gene,
bla
LUT-1
, was cloned from the whole-cell DNA of the
P. luteola
clinical isolate LAM, which had a weak narrow-spectrum β-lactam-resistant phenotype, and expressed in
Escherichia coli
. This gene encoded LUT-1, a 296-amino-acid Ambler class A β-lactamase with a pI of 6 and a theoretical molecular mass of 28.9 kDa. The catalytic efficiency of this enzyme was higher for cephalothin, cefuroxime, and cefotaxime than for penicillins. It was found to be 49% to 59% identical to other Ambler class A β-lactamases from
Burkholderia
sp. (PenA to PenL),
Ralstonia eutropha
(REUT),
Citrobacter sedlakii
(SED-1),
Serratia fonticola
(FONA and SFC-1),
Klebsiella
sp. (KPC and OXY), and CTX-M extended-spectrum β-lactamases. No gene homologous to the regulatory
ampR
genes of class A β-lactamases was found in the vicinity of the
bla
LUT-1
gene. The entire
bla
LUT-1
coding region was amplified by PCR and sequenced in five other genetically unrelated
P. luteola
strains (including the
P. luteola
type strain). A new variant of
bla
LUT-1
was found for each strain. These genes (named
bla
LUT-2
to
bla
LUT-6
) had nucleotide sequences 98.1 to 99.5% identical to that of
bla
LUT-1
and differing from this gene by two to four nonsynonymous single nucleotide polymorphisms. The
bla
LUT
gene was located on a 700- to 800-kb chromosomal I-CeuI fragment, the precise size of this fragment depending on the
P. luteola
strain.
Isolation and Characterization of Two Members of the Siderophore-Microcin Family, Microcins M and H47
Authors: Vassiliadis Gaëlle , Destoumieux-Garzón Delphine , Lombard Carine , Rebuffat Sylvie , Peduzzi Jean 
Published: November 2009

ABSTRACT

In this paper we provide the first biochemical evidence of the existence of a family of structure-related antimicrobial peptides, the siderophore-microcins, in the
Enterobacteriaceae
family. We isolated and characterized two novel siderophore-microcins, MccM and MccH47, previously characterized through genetic studies. MccM and MccH47 were expressed from several
Escherichia coli
strains containing the microcin gene clusters. The spectra of their bactericidal activities were found to be restricted to some species of the
Enterobacteriaceae
. MccM and MccH47 were unable to inhibit the growth of strains carrying mutations in the
fepA
,
cir
, and
fiu
genes, which showed the requirement of the iron-catecholate receptors for their recognition. The MccM and MccH47 peptide moieties contain 77 and 60 residues, respectively, and are derived from the microcin precursors McmA and MchB, respectively. In addition, both peptides carried a C-terminal posttranslational modification containing a salmochelin-like siderophore moiety also found in MccE492 (X. Thomas et al., J. Biol. Chem., 279:28233-28242, 2004). Interestingly, when MccM was isolated from
E. coli
Nissle 1917, which lacks the two genes necessary for modification biosynthesis, it was devoid of posttranslational modification. Those two genes could be complemented by their homologues from the MccH47 gene cluster, thereby showing their functional interchangeability between at least two members of the siderophore-microcin family. Finally, from the sequence analysis of the MccE492 gene cluster, we hypothesized the existence of an additional member of the siderophore-microcin family. Therefore, we propose that the siderophore-microcin family contains five representatives.
Pharmacokinetics and Safety of S/GSK1349572, a Next-Generation HIV Integrase Inhibitor, in Healthy Volunteers
Authors: Min Sherene , Song Ivy , Borland Julie , Chen Shuguang , Lou Yu , Fujiwara Tamio , Piscitelli Stephen C. 
Published: November 2009

ABSTRACT

S/GSK1349572 is a novel integrase inhibitor with potent
in vitro
anti-HIV activity, an
in vitro
resistance profile different from those of other integrase inhibitors, and favorable preclinical safety and pharmacokinetics (PK). Randomized, double-blind, placebo-controlled single-dose and multiple-dose, dose escalation studies evaluated the PK, safety, and tolerability of S/GSK1349572 for healthy subjects. In the single-dose study, two cohorts of 10 subjects each (8 active, 2 receiving placebo) received suspension doses of 2, 5, 10, 25, 50, and 100 mg in an alternating panel design. In the multiple-dose study, three cohorts of 10 subjects each (8 active, 2 receiving placebo) received suspension doses of 10, 25, and 50 mg once daily for 10 days. A cytochrome P450 3A (CYP3A) substudy with midazolam was conducted with the 25-mg dose. Laboratory testing, vital signs, electrocardiograms (ECGs), and PK sampling were performed at regular intervals. S/GSK1349572 was well tolerated. Most adverse events (AEs) were mild, with a few moderate AEs reported. Headache was the most common AE. No clinically significant laboratory trends or ECG changes were noted. PK was linear over the dosage range studied. The steady-state geometric mean area under the concentration-time curve over a dosing interval (AUC
0-τ
) and maximum concentration of the drug in plasma (
C
max
) ranged from 16.7 μg·h/ml (coefficient of variation [CV], 15%) and 1.5 μg/ml (CV, 24%) at a 10-mg dose to 76.8 μg·h/ml (CV, 19%) and 6.2 μg/ml (CV, 15%) at a 50-mg dose, respectively. The geometric mean steady-state concentration at the end of the dosing interval (
C
τ
) with a 50-mg dose was 1.6 μg/ml, approximately 25-fold higher than the protein-adjusted 90% inhibitory concentration (0.064 μg/ml). The half-life was approximately 15 h. S/GSK1349572 had no impact on midazolam exposure, indicating that it does not modulate CYP3A activity. The PK profile suggests that once-daily, low milligram doses will achieve therapeutic concentrations.
BEL-2, an Extended-Spectrum β-Lactamase with Increased Activity toward Expanded-Spectrum Cephalosporins in
Pseudomonas aeruginosa
Authors: Poirel Laurent , Docquier Jean-Denis , De Luca Filomena , Verlinde Annemie , Ide Louis , Rossolini Gian Maria , Nordmann Patrice 
Published: November 2009

ABSTRACT

A
Pseudomonas aeruginosa
isolate recovered in Belgium produced a novel extended-spectrum ß-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The
bla
BEL-2
gene was identified from a
P. aeruginosa
isolate clonally related to another
bla
BEL-1
-positive isolate.
Antimicrobial Resistance in
Haemophilus influenzae
Respiratory Tract Isolates in Korea: Results of a Nationwide Acute Respiratory Infections Surveillance
Authors: Bae Songmee , Lee Jaehoon , Lee Jaehwa , Kim Eunah , Lee Sunhwa , Yu Jaeyon , Kang Yeonho 
Published: November 2009

ABSTRACT

Antimicrobial susceptibility patterns and β-lactam resistance mechanisms of 544
Haemophilus influenzae
isolates through the nationwide Acute Respiratory Infections Surveillance (ARIS) network in Korea during 2005 and 2006 were determined. Resistance to ampicillin was 58.5%, followed by resistance to cefuroxime (23.3%), clarithromycin (18.7%), cefaclor (17.0%), amoxicillin-clavulanate (10.4%), and chloramphenicol (8.1%). Levofloxacin and cefotaxime were the most active agents tested in this study. β-Lactamase production (52.4%) was the main mechanism of ampicillin resistance, affecting 96.1% of TEM-1-type β-lactamase. According to their β-lactam resistance mechanisms, all isolates were classified into the following groups: β-lactamase-negative, ampicillin-sensitive (BLNAS) strains (
n
= 224; 41.5%); β-lactamase-positive, ampicillin-resistant (BLPAR) strains (
n
= 255; 47.2%); β-lactamase-negative, ampicillin-resistant (BLNAR) strains (
n
= 33; 6.1%); and β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) strains (
n
= 28; 5.2%). Among the BLNAR and BLPACR strains, there were various patterns of multiple-amino-acid substitutions in penicillin-binding protein 3. Particularly, among BLNAR, group III isolates, which had three simultaneous substitutions (Met377Ile, Ser385Thr, and Leu389Phe), were identified for the first time in Korea. Three group III strains displayed the highest MIC of cefotaxime (1 to 2 μg/ml). The results indicate the importance of monitoring a changing situation pertaining to the increase and spread of BLNAR and BLPACR strains of
H. influenzae
for appropriate antibiotic therapy for patients with respiratory tract infections in Korea.
In Vitro and In Vivo Activities of 1-Hydroxy-2-Alkyl-4(1
H
)Quinolone Derivatives against
Toxoplasma gondii
Authors: Bajohr Lara Liv , Ma Ling , Platte Christian , Liesenfeld Oliver , Tietze Lutz F. , Groß Uwe , Bohne Wolfgang 
Published: November 2009

ABSTRACT

1-Hydroxy-2-dodecyl-4(1
H
)quinolone (HDQ) was recently identified as a
Toxoplasma gondii
inhibitor. We describe here two novel 1-hydroxyquinolones, which displayed 50% inhibitory concentrations 10- and 5-fold lower than that of HDQ. In a mouse model of acute toxoplasmosis, these two compounds and HDQ reduced the percentages of infected peritoneal cells and decreased the parasite loads in lungs and livers. Compound B showed a tendency toward lowering parasite loads in brains in a mouse model of toxoplasmic encephalitis.