bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Rifalazil with Oxidant-Generating Systems of Human Polymorphonuclear Neutrophils
Authors: Labro M. T. , Ollivier V. , Babin-Chevaye C. 
Published: November 2005

ABSTRACT

It is well acknowledged that ansamycins display immunosuppressive and anti-inflammatory properties in vitro and in vivo. Rifalazil, a new ansamycin derivative, has not been studied in the context of inflammation. In particular, there are no data on the possible interference of rifalazil with oxidant production by phagocytes. We have compared the antioxidant properties of rifalazil to those of rifampin, a drug well known in this context, by using cellular and acellular oxidant-generating systems. Oxidant production by polymorphonuclear neutrophils was measured in terms of cytochrome
c
reduction, lucigenin-amplified chemiluminescence (Lu-ACL), and the 2′,7′-dichlorofluorescin diacetate H
2
(DCFDA-H
2
) technique (intracellular oxidant production). Rifalazil impaired O
2
−
production in a concentration-dependent manner, with 50% inhibitory concentrations (IC
50
) (concentrations which inhibit 50% of the response) of 5.4 (30 and 60 min of incubation) and 6.4 (30 min) mg/liter, respectively, for phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. In agreement with the published fMLP-like activity of rifampin, the inhibitory effect of rifampin was significantly greater for fMLP (IC
50
of 5.6 mg/liter) than for PMA (IC
50
of 58 mg/liter) stimulation. Alteration of intracellular oxidant production was also observed with IC
50
values similar to those obtained by the cytochrome assay. In addition, rifalazil and rifampin (≥25 mg/liter) scavenged O
2
−
, as demonstrated by the acellular (hypoxanthine-xanthine oxidase) system. Interference with light detection systems was evidenced for both drugs by Lu-ACL. The clinical relevance of the antioxidant effect of rifalazil demonstrated in vitro, in particular its potential anti-inflammatory activity, requires further investigation.
Alternative Pathway of Metronidazole Activation inTrichomonas vaginalisHydrogenosomes
Authors: Hrdý Ivan , Cammack Richard , Stopka Pavel , Kulda Jaroslav , Tachezy Jan 
Published: November 2005

ABSTRACTMetronidazole and related 5-nitroimidazoles are the only available drugs in the treatment of human urogenital trichomoniasis caused by the protozoan parasiteTrichomonas vaginalis. The drugs are activated to cytotoxic anion radicals by their reduction within the hydrogenosomes. It has been established that electrons required for metronidazole activation are released from pyruvate by the activity of pyruvate:ferredoxin oxidoreductase and transferred to the drug by a low-redox-potential carrier, ferredoxin. Here we describe a novel pathway involved in the drug activation within the hydrogenosome. The source of electrons is malate, another major hydrogenosomal substrate, which is oxidatively decarboxylated to pyruvate and CO2by NAD-dependent malic enzyme. The electrons released during this reaction are transferred from NADH to ferredoxin by NADH dehydrogenase homologous to the catalytic module of mitochondrial complex I, which uses ferredoxin as electron acceptor. Trichomonads acquire high-level metronidazole resistance only after both pyruvate- and malate-dependent pathways of metronidazole activation are eliminated from the hydrogenosomes.
Novel Cyclic Lipodepsipeptide from
Pseudomonas syringae
pv. lachrymans Strain 508 and Syringopeptin Antimicrobial Activities
Authors: Grgurina Ingeborg , Bensaci Mekki , Pocsfalvi Gabriella , Mannina Luisa , Cruciani Oscar , Fiore Alberto , Fogliano Vincenzo , Sorensen Kevin N. , Takemoto Jon Y. 
Published: November 2005

ABSTRACT

The syringopeptins are a group of antimicrobial cyclic lipodepsipeptides produced by several plant-associated pseudomonads. A novel syringopeptin, SP508, was shown to be produced as two homologs (A and B) by
Pseudomonas syringae
pv. lachrymans strain 508 from apple and to structurally resemble syringopeptin SP22. SP508 differed from SP22 and other syringopeptins by having three instead of four α,β-unsaturated amino acids and a longer β-hydroxy acyl chain. Both SP508 and SP22 displayed growth-inhibitory activities against
Mycobacterium smegmatis
, other gram-positive bacteria, and yeasts but not against gram-negative bacteria. Structure-activity analyses of the SP508 and SP22 homologs indicated chemical structural features that lead to enhanced antimycobacterial activity by these pseudomonad cyclic lipodepsipeptides.
Analysis of the Contribution of Individual Substituents in 4,6-Aminoglycoside-Ribosome Interaction
Authors: Hobbie Sven N. , Pfister Peter , Brüll Christian , Westhof Eric , Böttger Erik C. 
Published: November 2005

ABSTRACT

The 4,6-disubstituted 2-deoxystreptamines interfere with protein biosynthesis by specifically targeting the ribosomal A site. These drugs show subtle variations in the chemical groups of rings I, II, and III. In the present study we used site-directed mutagenesis to generate mutant strains of
Mycobacterium smegmatis
mc
2
155 SMR5 Δ
rrnB
with mutations in its single rRNA allele,
rrnA
. This genetic procedure gives rise to strains carrying homogeneous populations of mutant ribosomes and was used to study the contribution of individual chemical substituents to the binding of 4,6-disubstituted aminoglycosides. X-ray crystal structures of geneticin and tobramycin complexed to oligonucleotides containing the minimal bacterial ribosomal A site were used for interpretation of MICs determined for a panel of 4,6-aminoglycosides, including tobramycin, kanamycin A, kanamycin B, amikacin, gentamicin, and geneticin. Surprisingly, the considerable differences present within ring III did not seem to alter the interaction of the drug with the ribosome, as determined by site-directed mutagenesis of the A site. In contrast, subtle variations in ring I significantly influenced binding: (i) a 4′-hydroxyl moiety participates in the proper drug target interaction; and (ii) a 2′-amino group contributes an additional positive charge to ring I, making the drug less susceptible to any kind of sequence alteration within the decoding site, most notably, to conformational changes induced by transversion of U1495 to 1495A. The 4-amino-2-hydroxyl-1-oxobutyl extension at position 1 of ring II of amikacin provides an additional anchor and renders amikacin less dependent on the structural conformation of nucleotide U1406 compared to the dependencies of other kanamycins. Overall, the set of interactions forming the complex between drug substituents and nucleotides of the A site constitutes a network in which the interactions can partly compensate for each other when they are disrupted.
Type V Staphylococcal Cassette Chromosome
mec
in Community Staphylococci from Australia
Authors: O'Brien F. G. , Coombs G. W. , Pearson J. C. , Christiansen K. J. , Grubb W. B. 
Published: November 2005

ABSTRACT

Twenty Australian community staphylococci harboring the type V staphylococcal cassette chromosome
mec
(SCC
mec
) were found to belong to eight multilocus sequence types. Five were previously unreported novel type V SCC
mec
elements. The
mec
complexes were of two types, based on the polymorphisms in the IS
431
transposase genes. Five isolates were multiresistant.
In Vitro Activity of Ravuconazole against 923 Clinical Isolates of Nondermatophyte Filamentous Fungi
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Mellado Emilia , Garcia-Effron Guillermo , Monzon Araceli , Rodriguez-Tudela Juan Luis 
Published: November 2005

ABSTRACT

The in vitro activities of ravuconazole against 575 clinical strains of
Aspergillus
spp. and 348 nondermatophyte non-
Aspergillus
spp. were analyzed. Ravuconazole was active against
Aspergillus
spp., other hyaline filamentous fungi, black molds, and some
Mucorales
. Species such as
Scedosporium prolificans
,
Fusarium
spp., and
Scopulariopsis
spp. were resistant to the triazole.
Caspofungin and Liposomal Amphotericin B Therapy of Experimental Murine Scedosporiosis
Authors: Bocanegra Rosie , Najvar Laura K. , Hernandez Steve , McCarthy Dora I. , Graybill John R. 
Published: November 2005

ABSTRACT

Immunosuppressed mice were infected intravenously with conidia of
Scedosporium prolificans
. Treatment was begun 1 day later with liposomal amphotericin B, caspofungin, or both drugs initiated concurrently. Amphotericin B and caspofungin were each effective, but combined therapy did not appear to offer advantages over liposomal amphotericin B alone.
A New Method for Detection of Cirrus Overlapping Water Clouds and Determination of Their Optical Properties
Authors: Chang Fu-Lung , Li Zhanqing 
Published: November 2005

Abstract
The frequent occurrence of high cirrus overlapping low water cloud poses a major challenge in retrieving their optical properties from spaceborne sensors. This paper presents a novel retrieval method that takes full advantage of the satellite data from the Moderate Resolution Imaging Spectroradiometer (MODIS). The main objectives are identification of overlapped high cirrus and low water clouds and determination of their individual optical depths, top heights, and emissivities. The overlapped high cloud top is determined from the MODIS CO2-slicing retrieval and the underlying low cloud top is determined from the neighboring MODIS pixels that are identified as single-layer low clouds. The algorithm applies a dual-layer cloud radiative transfer model using initial cloud properties derived from the MODIS CO2-slicing channels and the visible (0.65 μm) and infrared (11 μm) window channels. An automated iterative procedure follows by adjusting the high cirrus and low water cloud optical depths until computed radiances from the dual-layer model match with observed radiances from both the visible and infrared channels. The algorithm is valid for both single-layer and dual-layer clouds with the cirrus optical depth &lt;∼4 (emissivity &lt;∼0.85). For more than two-layer clouds, its validity depends on the thickness of the upper-layer cloud. A preliminary validation is conducted by comparing against ground-based active remote sensing data. Pixel-by-pixel retrievals and error analyses are presented. It is demonstrated that retrievals based on a single-layer assumption can result in systematic biases in the retrieved cloud top and optical properties for overlapped clouds. Such biases can be removed or lessened considerably by applying the new algorithm.
Recent Advances in the Diagnosis and Treatment of Hypereosinophilic Syndromes
Authors: Klion Amy D. 
Published: November 2005

Abstract
Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by marked peripheral blood and tissue eosinophilia resulting in end organ damage. Recent advances in molecular biology and immunology have led to the identification of a number of distinct subtypes of HES with differing epidemiology, pathogenesis, and prognosis. The ability to distinguish between these HES subtypes combined with the availability of new treatment modalities, including tyrosine kinase inhibitors and monoclonal antibodies, that target specific molecules involved in disease pathogenesis have dramatically altered the approach to the diagnosis and treatment of HES.
Solitary Bone and Extramedullary Plasmacytoma
Authors: Weber Donna M. 
Published: November 2005

Abstract
Less than 5% of patients with a plasma cell dyscrasia present with a single bone (SBP) or extramedullary plasmacytoma (EMP) without evidence of systemic disease (normocalcemia, absence of anemia, preservation of uninvolved immunoglobulins, or renal disease attributable to myeloma). Diagnosis requires biopsy confirmation of a monoclonal plasma cell infiltrate from a single site. The treatment of choice for both entities is radiotherapy given with curative intent (> 4000 cGy) resulting in long term disease-free survival in approximately 30% of patients with SBP and 65% of patients with EMP.
Pathogenesis of Atherosclerosis
Authors: Crowther Mark A. 
Published: November 2005

Abstract
Atherosclerosis is no longer considered a disorder due to abnormalities in lipid metabolism. In fact, the inciting event of atherosclerosis is likely an inflammatory insult that occurs decades before the disease becomes clinically apparent. Rapidly evolving knowledge of the pathogenesis of atherosclerosis, coupled with novel, target-specific therapies, is revolutionizing the treatment of atherosclerosis. As a result, a variety of treatments are now undergoing evaluation for their ability to ameliorate the inflammatory pathways likely to cause the atherosclerotic process to initiate and propagate. Once initiated, atherosclerosis progresses as a result of a well-studied series of changes in the constituent cellular make-up of the vessel wall. Specific cytokine-mediated events in this cycle are required for lesional growth. The clinical manifestations of atherosclerosis occur so late in this process that interventions such as percutaneous coronary interventions can deal with isolated areas of disease; however, they do not influence the underlying disease process.
Considerations for Adult Cancer Survivors
Authors: Tichelli André , Socié Gérard 
Published: November 2005

Abstract
With improvements in outcome, increased numbers of adult cancer patients survive free of their primary malignancy. Today, about 60% of adult patients diagnosed with cancer will survive 5 years after diagnosis. Therefore, immediate survival is no longer the sole concern. The aim of the cancer treatment now is to cure a patient’s underlying disease and, at the same time, to minimize the incidence of post-treatment complications and ensure the best possible long term quality of life. The long time span between initial therapy and late effects, the multiple factors influencing cancer-related health risk and the unknown effect of treatment on normal aging are common characteristics of late effects. While the treatment strategy for a cancer patient depends widely on the type and extension of the disease, considerations for a long-term survivor depend much more on the type of treatment applied, age of the patient, and the patient’s general health status as well as his or her familial and social integration. We discuss, based on the most recent knowledge, some typical examples of late effects in cancer survivors and the practical recommendations that could assist practitioner and patient decision about appropriate healthcare for specific clinical circumstances.
An Evidence-Based Approach to the Treatment of Adults with Sickle Cell Disease
Authors: Lottenberg Richard , Hassell Kathryn L. 
Published: November 2005

Abstract
The application of evidence-based medicine to the management of adults with sickle cell disease (SCD) is currently primarily driven by clinical expertise and patient preference, as there is a paucity of randomized controlled trial (RCT) data to guide decision-making. A summary of SCD management principles in the areas of health care maintenance, transfusion therapy, treatment and prevention of painful episodes, acute chest syndrome, stroke, renal disease, contraception and pregnancy, and priapism is predominantly based on the authors’ interpretation of available observational studies as well as the opinions of experts in SCD. RCTs impacting current practices address use of hydroxyurea to prevent painful episodes and acute chest syndrome, intensity of pre-operative transfusion, transfusion during pregnancy, and angiotensin-converting enzyme inhibitor therapy for proteinuria, but most issues in adult SCD care have not been rigorously studied and management may not be appropriately extrapolated from pediatric data. While challenging clinical problems need to be addressed by RCTs, there is also the need for development of practice guidelines using formal methodological strategies. This brief review is not a substitute for the process but provides a literature-based approach to making treatment decisions when caring for adults with SCD.
The Enhancer of split and Achaete-Scute complexes of Drosophilids derived from simple ur-complexes preserved in mosquito and honeybee
Authors: Schlatter Rebekka , Maier Dieter 
Published: November 2005

Abstract

Background
In Drosophila melanogaster the Enhancer of split-Complex [E(spl)-C] consists of seven highly related genes encoding basic helix-loop-helix (bHLH) repressors and intermingled, four genes that belong to the Bearded (Brd) family. Both gene classes are targets of the Notch signalling pathway. The Achaete-Scute-Complex [AS-C] comprises four genes encoding bHLH activators. The question arose how these complexes evolved with regard to gene number in the evolution of insects concentrating on Diptera and the Hymenoptera Apis mellifera.

Results
In Drosophilids both gene complexes are highly conserved, spanning roughly 40 million years of evolution. However, in species more diverged like Anopheles or Apis we find dramatic differences. Here, the E(spl)-C consists of one bHLH (mβ) and one Brd family member (mα) in a head to head arrangement. Interestingly in Apis but not in Anopheles, there are two more E(spl) bHLH like genes within 250 kb, which may reflect duplication events in the honeybee that occurred independently of that in Diptera. The AS-C may have arisen from a single sc/l'sc like gene which is well conserved in Apis and Anopheles and a second ase like gene that is highly diverged, however, located within 50 kb.

Conclusion

E(spl)-C and AS-C presumably evolved by gene duplication to the nowadays complex composition in Drosophilids in order to govern the accurate expression patterns typical for these highly evolved insects. The ancestral ur-complexes, however, consisted most likely of just two genes: E(spl)-C contains one bHLH member of mβ type and one Brd family member of mα type and AS-C contains one sc/l'sc and a highly diverged ase like gene.
Office bladder distention with Electromotive Drug Administration (EMDA) is equivalent to distention under General Anesthesia (GA)
Authors: Rose Amy E , Azevedo Kathryn J , Payne Christopher K 
Published: November 2005

Abstract

Background
Bladder distention is commonly used in diagnosis and treatment of interstitial cystitis (IC). Traditionally performed in the operating room under general or spinal anesthesia (GA), it is expensive and associated with short term morbidity. Office bladder distention using electromotive drug administration (EMDA) has been suggested as an alternative that is well tolerated by patients. We report the first comparative findings of patients undergoing both office distention with EMDA and distention in the operating room (OR) with GA.

Methods
This retrospective chart review identified 11 patients participating in two protocols of EMDA bladder distention who also underwent bladder distention under GA either prior to or after the EMDA procedure.

Results
The median absolute difference in bladder capacity between GA and EMDA was only 25 cc; the median percent difference was 5%. Cystoscopic findings, while not prospectively compiled, appear to have been similar.

Conclusion
This study represents the first comparison between distention with EMDA versus GA and confirms the technical feasibility of performing bladder distention in an office setting. The distention capacity achieved in the office was nearly identical to that in the OR and the cystoscopic findings very similar. Further investigation into the comparative morbidity, cost, and other outcome measures is warranted to define the ultimate role of EMDA bladder distention in the clinical evaluation and care of patients with IC.
A systematic review of existing national priorities for child health research in sub-Saharan Africa
Authors: Swingler George H , Irlam James H , Macharia William M , Tietche Félix , Meremikwu Martin M 
Published: November 2005

Abstract

Background
We systematically reviewed existing national child health research priorities in Sub-Saharan Africa, and the processes used to determine them.

Methods
Collaborators from a purposive sample of 20 WHO-AFRO Region countries, assisted by key informants from a range of governmental, non-governmental, research and funding organisations and universities, identified and located potentially eligible prioritisation documents. Included documents were those published between 1990 and 2002 from national or nationally accredited institutions describing national health research priorities for child health, alone or as part of a broader report in which children were a clearly identifiable group. Laboratory, clinical, public health and policy research were included. Two reviewers independently assessed eligibility for inclusion and extracted data.

Results
Eight of 33 potentially eligible reports were included. Five reports focused on limited areas of child health. The remaining three included child-specific categories in reports of general research priorities, with two such child-specific categories limited to reproductive health. In a secondary analysis of Essential National Health Research reports that included children, though not necessarily as an identifiable group, the reporting of priorities varied markedly in format and numbers of priorities listed, despite a standard recommended approach. Comparison and synthesis of reported priorities was not possible.

Conclusion
Few systematically developed national research priorities for child health exist in sub-Saharan Africa. Children's interests may be distorted in prioritisation processes that combine all age groups. Future development of priorities requires a common reporting framework and specific consideration of childhood priorities.
Genetic mechanisms of knee osteoarthritis: a population-based longitudinal study
Authors: Ding Changhai , Cicuttini Flavia , Blizzard Leigh , Jones Graeme 
Published: November 2005

AbstractTo describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.