bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by probenecid
Authors: Landersdorfer Cornelia B. , Kirkpatrick Carl M. J. , Kinzig Martina , Bulitta Jürgen B. , Holzgrabe Ulrike , Jaehde Ulrich , Reiter Andreas , Naber Kurt G. , Rodamer Michael , Sörgel Fritz 
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Probenecid inhibits the active transport of both anionic and cationic drug molecules at various sites in the body.• Probenecid has been reported to decrease the elimination of several quinolones.• We are not aware of any reports where a mechanism‐based model for the interaction of quinolones and probenecid in humans or animals has been developed.WHAT THIS STUDY ADDS• Pharmacokinetic modelling indicates competitive inhibition of the renal tubular secretion of ciprofloxacin and its metabolite M1 by probenecid.• The affinity for the renal transporter was 4.4 times higher for ciprofloxacin and 3.6 times higher for M1 compared with probenecid, based on molar concentrations.• Probenecid did not affect volume of distribution of ciprofloxacin or M1, nonrenal clearance or intercompartmental clearance of ciprofloxacin.AIMSProbenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites.METHODSA randomized, two‐way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532–41). Subjects received 200 mg ciprofloxacin as 30‐min intravenous infusion without and with 3 g probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography–tandem mass spectrometry and high‐performance liquid chromatography. Ciprofloxacin and its 2‐aminoethylamino‐metabolite (M1) in plasma and urine with and without probenecid were modelled simultaneously with WinNonlin®.RESULTSData are ratio of geometric means (90% confidence intervals). Addition of probenecid reduced the median renal clearance from 23.8 to 8.25 l h−1[65% reduction (59, 71),P < 0.01] for ciprofloxacin and from 20.5 to 8.26 l h−1(66% reduction (57, 73),P < 0.01] for M1 (estimated by modelling). Probenecid reduced ciprofloxacin nonrenal clearance by 8% (1, 14) (P < 0.08). Pharmacokinetic modelling indicated competitive inhibition of the renal tubular secretion of ciprofloxacin and M1 by probenecid. The affinity for the renal transporter was 4.4 times higher for ciprofloxacin and 3.6 times higher for M1 than for probenecid, based on the molar ratio. Probenecid did not affect volume of distribution of ciprofloxacin or M1, nonrenal clearance or intercompartmental clearance of ciprofloxacin.CONCLUSIONSProbenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100‐fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected.
Effects of nicotine on cytochrome P450 2A6 and 2E1 activities
Authors: Hukkanen Janne , Jacob III Peyton , Peng Margaret , Dempsey Delia , Benowitz Neal L. 
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone.• Nicotine is a useful probe for phenotyping cytochrome P450 2A6 activity and chlorzoxazone is a frequently used probe for CYP2E1 activity.• The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities are unknown.WHAT THIS PAPER ADDS• This study demonstrates that CYP2A6 and CYP2E1 activities are not affected by nicotine dosing.• High‐dose nicotine treatment has a low potential of interaction with CYP2A6 and CYP2E1 substrates.• The mechanisms of tobacco smoke‐elicited changes in CYP2A6 and CYP2E1 activities are yet to be determined.AIMSSmoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking.METHODSThe study had a single‐blind, randomized, crossover two‐arm design. Twelve healthy smokers were given two transdermal patches with 42‐mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium‐labelled nicotine‐d2and cotinine‐d4infusion on day 8.RESULTSThere was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine‐d2or on the formation of cotinine‐d2. Nicotine decreased the volume of distribution (62.6vs.67.7 l, 95% confidence interval of the difference −9.7, −0.6,P= 0.047) of infused cotinine‐d4. There were no significant differences in disposition kinetics of chlorzoxazone between the treatments.CONCLUSIONSCYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown.
High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus
Authors: Hartmann Sylvia , Gesk Stefan , Scholtysik René , Kreuz Markus , Bug Stefanie , Vater Inga , Döring Claudia , Cogliatti Sergio , Parrens Marie , Merlio Jean‐Philippe , Kwiecinska Anna , Porwit Anna , Piccaluga Pier Paolo , Pileri Stefano , Hoefler Gerald , Küppers Ralf , Siebert Reiner , Hansmann Martin‐Leo 
Published: October 2009

SummaryLittle is known about genomic aberrations in peripheral T cell lymphoma, not otherwise specified (PTCL NOS). We studied 47 PTCL NOS by 250k GeneChip single nucleotide polymorphism arrays and detected genomic imbalances in 22 of the cases. Recurrent gains and losses were identified, including gains of chromosome regions 1q32–43, 2p15–16, 7, 8q24, 11q14–25, 17q11–21 and 21q11–21 (≥5 cases each) as well as losses of chromosome regions 1p35–36, 5q33, 6p22, 6q16, 6q21–22, 8p21–23, 9p21, 10p11–12, 10q11–22, 10q25–26, 13q14, 15q24, 16q22, 16q24, 17p11, 17p13 and Xp22 (≥4 cases each). Genomic imbalances affected several regions containing members of nuclear factor‐kappaB signalling and genes involved in cell cycle control. Gains of 2p15–16 were confirmed in each of three cases analysed by fluorescence in situ hybridization (FISH) and were associated with breakpoints at the REL locus in two of these cases. Three additional cases with gains of the REL locus were detected by FISH among 18 further PTCL NOS. Five of 27 PTCL NOS investigated showed nuclear expression of the REL protein by immunohistochemistry, partly associated with genomic gains of the REL locus. Therefore, in a subgroup of PTCL NOS gains/rearrangements of REL and expression of REL protein may be of pathogenetic relevance.
Coudability hairs: a revisited sign of alopecia areata assessed by trichoscopy
Authors: Inui S. , Nakajima T. , Itami S. 
Published: October 2009

Summary
Background. We have previously reported several trichoscopic (dermatoscopic) characteristics, such as black dots, ‘exclamation-mark’ hairs, broken hairs, yellow dots and clustered short vellus hairs as being useful clinical indicators for alopecia areata (AA). ‘Coudability hairs’, which are normal-looking hairs tapered at the proximal end, have been previously reported as another sign of AA.
Aims. To use trichoscopy to evaluate coudability hairs as a clinical indicator for the disease activity of AA and a substitute-marker for the hair-pull test.
Methods. Trichoscopic examinations of hair loss and perilesional areas on the scalps of 100 East Asian patients with AA were performed using a dermatoscope. Using Spearman’s rank-order correlation coefficient by rank test, we examined the correlations of scores between coudability and AA disease activity, severity or duration and other trichoscopic features, and then evaluated the coudability score as a surrogate-marker for the hair-pull test.
Results. Coudability scores correlated positively with AA disease activity, hair-pull tests, short duration, black dots and exclamation-mark hairs, and correlated negatively with short vellus hairs.
Conclusions. Coudability hairs, more closely perceived by trichoscopy, are useful-markers for disease activity in AA and provide a surrogate-marker for the hair-pull test.
Effects of hyaluronan and iodine on wound contraction and granulation tissue formation in rat skin wounds
Authors: Slavkovsky R. , Kohlerova R. , Jiroutova A. , Hajzlerova M. , Sobotka L. , Cermakova E. , Kanta J. 
Published: October 2009

Summary
Background. Hyaluronan (HA) plays an important role in the repair of damaged skin and has been used for the treatment of wounds. Iodine is a mild topical antiseptic.
Aim. A mixture of high molecular weight HA with the iodine complex KI3 (hyiodine) was reported to accelerate wound healing in patients with diabetes and patients after surgery. We investigated how this mixture affects wound contraction, granulation tissue (GT) and wound edges in excision skin wounds in rats.
Methods. Hyiodine was applied to full-thickness wounds made on the back of rats. The areas of the contracting wounds were calculated from digital photographs. The moving edges of the wound were studied by histological methods. The properties of GT were studied in wounds in which contraction was prevented by the insertion of plastic rings. The effects of hyiodine were compared with those of high molecular weight (1200 kDa) HA, low molecular weight (11 kDa) HA and KI3 solution.
Results. Hyiodine accelerated wound contraction significantly in the first 5 days of healing. On day 3, hyiodine-treated wounds had reduced to 63% of the original area, whereas the wound area in saline-treated animals was 75% of the original size. The proliferating epidermis was thicker in hyiodine-treated animals on day 7. In the wounds with inserted rings, hyiodine caused little change in GT, but the weight of the crust/exudate formed on the top of the wound was increased by 351% compared with only minor changes caused by the hyiodine components alone.
Conclusions. Hyiodine supports wound healing by stimulating wound contraction and epidermal proliferation and by keeping the wound moist through increased exudation.
Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis
Authors: Rębała K. , Szczerkowska-Dobosz A. , Niespodziana K. , Wysocka J. 
Published: October 2009

Summary
Background. The human leucocyte antigen (HLA) C allele Cw*06 is currently recognized as a major disease allele at the PSORS1 locus. It has been suggested that characterization of this gene could be used as a convenient criterion for classification of psoriasis phenotypes.
Aim. To design and optimize a DNA typing procedure, suitable for identification of HLA-Cw*06 and its zygosity status verification in large-scale analyses, and to test for its robustness in a case–control study.
Methods. PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-Cw*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-Cw*06. Additionally, those homozygous for HLA-Cw*06 were screened for nonspecific digestion by degenerated PCR-SSP. This three-step procedure was used in the examination of 383 patients with psoriasis that developed at the age of ≥ 30 years of age and of 143 healthy subjects from northern Poland.
Results. A simple and rapid procedure for screening of HLA-Cw*06 was produced. A significant difference in HLA-Cw*06 frequency between patients with psoriasis and controls was seen (P = 0.02). Detailed examination of the age of disease onset among patients with psoriasis revealed that involvement of HLA-Cw*06 in the genetic background of psoriasis developing as late as the age of 45 years cannot be neglected.
Conclusions. The low cost, high-throughput capacity and requirement for small sample amounts make this procedure a useful one for HLA-Cw*06 typing in clinical practice and large population studies. We recommend that patients with psoriasis diagnosed before 45 years of age should be considered for diagnostic HLA-Cw*06 typing.
Severe exacerbation of multiple self-healing squamous epithelioma (Ferguson–Smith disease) with radiotherapy, which was successfully treated with acitretin
Authors: Robertson S. J. , Bashir S. J. , Pichert G. , Robson A. , Whittaker S. 
Published: October 2009

Summary
We describe the challenging case of a patient presenting with extensive, eruptive mid-facial squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) consequent to radiotherapy. Our patient had a personal and family history of multiple KAs and SCCs. Multiple self-healing squamous epithelioma, otherwise known as Ferguson–Smith disease, was diagnosed. This case presented a therapeutic challenge to preserve tissue and avoid severe facial disfigurement. We found oral acitretin to be the treatment of choice.
Management of acne vulgaris: an evidence-based update
Authors: Ingram J. R. , Grindlay D. J. C. , Williams H. C. 
Published: October 2009

SummaryThis review summarizes clinically important findings from 3 systematic reviews, 1 updated guideline and a selection from the 62 randomized controlled trials (RCTs) published between February 2007 and January 2009 on the topic of acne vulgaris. Low glycaemic-load diets might reduce acne severity but this remains unproven. Written patient information leaflets have not been surpassed by other communication methods. New combination topical treatments have not shown convincing advantages over current combination products such as clindamycin/benzoyl peroxide. Topical dapsone is superior to placebo but has yet to be compared with standard topical treatments. Long-term topical tretinoin to prevent nonmelanoma skin cancer in elderly men was associated with higher all-cause mortality, but there is currently no evidence of increased mortality for topical retinoid use when treating acne. All oral tetracyclines have similar efficacy, yet minocycline is the most costly. Oral isotretinoin monotherapy remains the gold-standard treatment for severe acne. Flutamide plus the oral contraceptive pill is beneficial for acne associated with polycystic ovary syndrome. Photodynamic therapy, phototherapy and laser therapy cannot be recommended universally for acne until minimal postinflammatory pigmentation and longer-term benefit can be shown, especially with current high costs. Development of non-antibiotic therapies is preferable to minimize the risk of community antibiotic resistance. Future trials should use active comparators at optimum doses and avoid noninferiority comparisons unless appropriately powered. Trials need to shift from using multiple, unvalidated outcome measures to including patient-reported and quality-of-life outcomes, and all trials should be registered on a public clinical-trials database.
Postirradiation linear morphoea
Authors: Akay B. N. , Sanli H. , Heper A. O. 
Published: October 2009

Summary
Postirradiation morphoea is an uncommon side-effect of radiotherapy. We report a 74-year-old woman who was treated with radiotherapy for endometrial carcinoma. About 3.5 years after the first dose of radiotherapy, the patient developed linear morphoea starting from the radiation port and affecting distant, nonirradiated skin. Lesions of radiation-induced morphoea are generally described as well-demarcated, indurated plaques with varying amounts of associated erythema; however, there is no previous publication of unilateral band-like distribution of morphoea associated with radiotherapy, to our knowledge.
Allergic women show reduced T helper type 1 alloresponses to fetal human leucocyte antigen mismatch during pregnancy
Authors: Prescott S L , Breckler L A , Witt C S , Smith L , Dunstan J A , Christiansen F T 
Published: October 2009

SummaryLow-level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno–fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non-allergic women (n = 65). HLA-DRβ1 mismatch was associated with significantly increased Th1 interferon (IFN)-γ, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-γ Th1 production in response to HLA-DRβ1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-γ production relative to IL-13. Both HLA-DRβ1 mismatch and maternal allergy had significant independent effects on maternal IFN-γ Th1 responses. Maternal allergy modifies HLA-mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno–fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.
Hydrological and biogeochemical controls on the timing and magnitude of nitrous oxide flux across an agricultural landscape
Authors: CASTELLANO MICHAEL J. , SCHMIDT JOHN P. , KAYE JASON P. , WALKER CHARLES , GRAHAM CHRIS B. , LIN HENRY , DELL CURTIS J. 
Published: October 2009

AbstractAnticipated increases in precipitation intensity due to climate change may affect hydrological controls on soil N2O fluxes, resulting in a feedback between climate change and soil greenhouse gas emissions. We evaluated soil hydrologic controls on N2O emissions during experimental water table fluctuations in large, intact soil columns amended with 100 kg ha−1 KNO3‐N. Soil columns were collected from three landscape positions that vary in hydrological and biogeochemical properties (N= 12 columns). We flooded columns from bottom to surface to simulate water table fluctuations that are typical for this site, and expected to increase given future climate change scenarios. After the soil was saturated to the surface, we allowed the columns to drain freely while monitoring volumetric soil water content, matric potential and N2O emissions over 96 h. Across all landscape positions and replicate soil columns, there was a positive linear relationship between total soil N and the log of cumulative N2O emissions (r2= 0.47; P= 0.013). Within individual soil columns, N2O flux was a Gaussian function of water‐filled pore space (WFPS) during drainage (mean r2= 0.90). However, instantaneous maximum N2O flux rates did not occur at a consistent WFPS, ranging from 63% to 98% WFPS across landscape positions and replicate soil columns. In contrast, instantaneous maximum N2O flux rates occurred within a narrow range (−1.88 to −4.48 kPa) of soil matric potential that approximated field capacity. The relatively consistent relationship between maximum N2O flux rates and matric potential indicates that water filled pore size is an important factor affecting soil N2O fluxes. These data demonstrate that matric potential is the strongest predictor of the timing of N2O fluxes across soils that differ in texture, structure and bulk density.
Carbon bio‐sequestration within the phytoliths of economic bamboo species
Authors: PARR JEFFREY , SULLIVAN LEIGH , CHEN BIHUA , YE GONGFU , ZHENG WEIPENG 
Published: October 2009

AbstractThe rates of carbon bio‐sequestration within silica phytoliths of the leaf litter of 10 economically important bamboo species indicates that (a) there is considerable variation in the content of carbon occluded within the phytoliths (PhytOC) of the leaves between different bamboo species, (b) this variation does not appear to be directly related to the quantity of silica in the plant but rather the efficiency of carbon encapsulation by the silica. The PhytOC content of the species under the experimental conditions ranged from 1.6% to 4% of the leaf silica weight. The potential phytolith carbon bio‐sequestration rates in the leaf‐litter component for the bamboos ranged up to 0.7 tonnes of carbon dioxide (CO2) equivalents (t‐e‐CO2) ha−1 yr−1 for these species. Assuming a median phytolith carbon bio‐sequestration yield of 0.36 t‐e‐CO2 ha−1 yr−1, the global potential for bio‐sequestration via phytolith carbon (from bamboo and/or other similar grass crops) is estimated to be ∼1.5 billion t‐e‐CO2 yr−1, equivalent to 11% of the current increase in atmospheric CO2. The data indicate that the management of vegetation such as bamboo forests to maximize the production of PhytOC has the potential to result in considerable quantities of securely bio‐sequestered carbon.
A common haplotype of protamine 1 and 2 genes is associated with higher sperm counts
Authors: Tüttelmann F. , Křenková P. , Römer S. , Nestorovic A. R. , Ljujic M. , Štambergová A. , Macek Jr M. , Macek Sr M. , Nieschlag E. , Gromoll J. , Simoni M. 
Published: October 2009

SummarySperm chromatin compaction in the sperm head is achieved when histones are replaced by protamines during spermatogenesis. Haploinsufficiency of the protamine 1 (PRM1) or PRM2 gene causes infertility in mice. However, the published data remain inconclusive about a role of PRM1/2 variants in male infertility and their association with semen parameters. By full sequence analysis, we assessed the frequency of sequence variations in PRM1 and PRM2 in three groups of Caucasian patients with idiopathic teratozoospermia and normal (n = 88) or reduced sperm concentration (n = 83) and in men with a high percentage of normal sperm morphology and normal concentrations (n = 77). Two rare (c.54G>A and c.102G>T) and one common SNP (c.230A>C) were identified in PRM1. In PRM2, some rare heterozygous mutations and the two common intronic SNPs 298G>C and 373C>A were detected. None of the PRM1/2 variants was associated with teratozoospermia or individually with other semen parameters. However, significant linkage disequilibrium was detected between the common SNPs of PRM1 and PRM2 which formed haplotypes. Analysis of the pooled group (n = 248) revealed that homozygous carriers of the common haplotype ACC had a twofold higher sperm concentration and count than men lacking this haplotype, with sperm counts of heterozygotes for ACC being midway between the homozygotes. This markedly decreased sperm output might either be caused by spermatozoa lacking the ACC haplotype not being viable, or subject to negative selection. In addition, a significant deviation from Hardy–Weinberg‐Equilibrium of these SNPs might indicate natural selection in favour of the ACC allele which leads to higher sperm output and therefore better fertility. In conclusion, for the first time we describe an association of a common haplotype formed by PRM1 and PRM2 with sperm output in a large group of men.