bluuebunny/crossref_metadata_2025 huggingface dataset:
Tidal Volume Lower than 6 ml/kg Enhances Lung Protection
Authors: Terragni Pier Paolo , Del Sorbo Lorenzo , Mascia Luciana , Urbino Rosario , Martin Erica L. , Birocco Alberto , Faggiano Chiara , Quintel Michael , Gattinoni Luciano , Ranieri V Marco
Published: September 2009

Background

Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal.

Methods

PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h.

Results

Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed.

Conclusions

VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.
Epidural Cooling Minimizes Spinal Cord Injury after Aortic Cross-clamping through Induction of Nitric Oxide Synthase
Authors: Ishikawa Akiko , Mori Atsuo , Kabei Nobuyuki , Yoshitake Akihiro , Suzuki Takeshi , Katori Nobuyuki , Morisaki Hiroshi , Yozu Ryohei , Takeda Junzo
Published: September 2009

Background

By using a U-shaped lumen catheter, the authors examined the effects of epidural cooling on spinal cord injury after aortic cross-clamping (ACC), with a focus on changes of spinal cord blood flow and expression of inducible nitric oxide synthase.

Methods

Sixteen pigs were randomized into two groups: Control group (n = 8) or Cooling group (n = 8). In the latter, epidural cooling started at 30 min (baseline) before 45 min of ACC and persisted for the next 30 min of reperfusion period. Spinal cord blood flow and somatosensory-evoked potentials were assessed during peri-ACC period. At 48 h, we evaluated hind limb function by using Tarlov score and expression of inducible nitric oxide synthase on spinal cord using immunohistochemistry.

Results

After ACC, spinal cord blood flow dropped to a similar extent in both groups. During the reperfusion period, spinal cord blood flow increased up to 113% (103-124%), median (interquartile range), level transiently and decreased to 32% (22-47%) level versus baseline in the Control group, whereas it increased and remained at 92% (86-97%) level in the Cooling group. Simultaneously, somatosensory-evoked potentials showed that onset of loss time was delayed and recovery time was shortened in the Cooling group. Tarlov scores in the Cooling group were significantly higher and accompanied by normal-appearing motor neurons and significantly greater expression of inducible nitric oxide synthase on spinal cord versus the Control group.

Conclusions

This study shows that epidural cooling during ACC minimized the risk of spinal cord injury, possibly by preventing delayed hypoperfusion and upregulating inducible nitric oxide synthase expression.
A Population-based Analysis of Outpatient Colonoscopy in Adults Assisted by an Anesthesiologist
Authors: Alharbi Othman , Rabeneck Linda , Paszat Lawrence F. , Wijeysundera Duminda N. , Sutradhar Rinku , Yun Lingsong , Vinden Christopher M. , Tinmouth Jill
Published: September 2009

Background

The use of propofol to sedate patients for colonoscopy, generally administered by an anesthesiologist in North America, is increasingly popular. In the United States, regional use of anesthesiologist-assisted endoscopy appears to correlate with local payor policy. This study's objective was to identify nonpayor factors (patient, physician, institution) associated with anesthesiologist assistance at colonoscopy.

Methods

The authors performed a population-based cross-sectional analysis using Ontario health administrative data, 1993-2005. All outpatient colonoscopies performed on adults were identified. Hierarchical multivariable modeling was used to identify patient (age, sex, income quintile, comorbidity), physician (specialty, colonoscopy volume), and institution (type, volume) factors associated with receipt of anesthesiologist-assisted colonoscopy.

Results

During the study period, 1,838,879 colonoscopies were performed on 1,202,548 patients. The proportion of anesthesiologist-assisted colonoscopies rose from 8.4% in 1993 to 19.1% in 2005 (P < 0.0001). In the hierarchical model, patients in low-volume community hospitals were five times more likely to receive anesthesiologist-assisted colonoscopy than patients in high-volume community hospitals (odds ration 4.9; 95% confidence interval 4.4-5.5). Less than 1% of colonoscopies in academic hospitals were anesthesiologist-assisted. Compared to gastroenterologists, surgeons were more likely to perform anesthesiologist-associated colonoscopy (odds ratio 1.7; 95% confidence interval 1.1-2.6).

Conclusions

In Ontario, rates of anesthesiologist-assisted colonoscopy have risen dramatically. Institution type was most strongly associated with this practice. Further investigation is needed to determine the most appropriate criteria for the use of anesthesiology services during colonoscopy.
Early Phase Pharmacokinetics but Not Pharmacodynamics Are Influenced by Propofol Infusion Rate
Authors: Masui Kenichi , Kira Marimo , Kazama Tomiei , Hagihira Satoshi , Mortier Eric P. , Struys Michel M. R. F.
Published: September 2009

Background

Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model.

Methods

Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure.

Results

Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate.

Conclusions

This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.
Response Surface Modeling of the Interaction between Propofol and Sevoflurane
Authors: Schumacher Peter M. , Dossche Jan , Mortier Eric P. , Luginbuehl Martin , Bouillon Thomas W. , Struys Michel M. R. F.
Published: September 2009

Background

Propofol and sevoflurane display additivity for gamma-aminobutyric acid receptor activation, loss of consciousness, and tolerance of skin incision. Information about their interaction regarding electroencephalographic suppression is unavailable. This study examined this interaction as well as the interaction on the probability of tolerance of shake and shout and three noxious stimulations by using a response surface methodology.

Methods

Sixty patients preoperatively received different combined concentrations of propofol (0-12 microg/ml) and sevoflurane (0-3.5 vol.%) according to a crisscross design (274 concentration pairs, 3 to 6 per patient). After having reached pseudo-steady state, the authors recorded bispectral index, state and response entropy and the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy. For the analysis of the probability of tolerance by logistic regression, a Greco interaction model was used. For the separate analysis of bispectral index, state and response entropy suppression, a fractional Emax Greco model was used. All calculations were performed with NONMEM V (GloboMax LLC, Hanover, MD).

Results

Additivity was found for all endpoints, the Ce(50, PROP)/Ce(50, SEVO) for bispectral index suppression was 3.68 microg. ml(-1)/ 1.53 vol.%, for tolerance of shake and shout 2.34 microg . ml(-1)/ 1.03 vol.%, tetanic stimulation 5.34 microg . ml(-1)/ 2.11 vol.%, laryngeal mask airway insertion 5.92 microg. ml(-1) / 2.55 vol.%, and laryngoscopy 6.55 microg. ml(-1)/2.83 vol.%.

Conclusion

For both electroencephalographic suppression and tolerance to stimulation, the interaction of propofol and sevoflurane was identified as additive. The response surface data can be used for more rational dose finding in case of sequential and coadministration of propofol and sevoflurane.
Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc
Authors: Peng H. Wayne , Slattery Matthew , Mann Richard S.
Published: September 2009

The accurate control of cell proliferation and survival is critical for animal development. The Hippo tumor suppressor pathway regulates both of these parameters by controlling the nuclear availability of the transcriptional coactivator Yorkie (Yki), which regulates downstream target genes together with Scalloped (Sd), a DNA-binding protein. Here we provide evidence that Yki can also regulate target genes in conjunction with Homothorax (Hth) and Teashirt (Tsh), two DNA-binding transcription factors expressed in the uncommitted progenitor cells of the Drosophila eye imaginal disc. Clonal analyses demonstrate that Hth and Tsh promote cell proliferation and protect eye progenitor cells from apoptosis. Genetic epistasis experiments suggest that Hth and Tsh execute these functions with Yki, in part by up-regulating the microRNA bantam. A physical interaction between Hth and Yki can be detected in cell culture, and we show that Hth and Yki are bound to a DNA sequence ∼14 kb upstream of the bantam hairpin in eye imaginal disc cells, arguing that this regulation is direct. These data suggest that the Hippo pathway uses different DNA-binding transcription factors depending on the cellular context. In the eye disc, Hth and Tsh provide spatial information to this pathway, promoting cell proliferation and survival in the progenitor domain.
XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy
Authors: Hetz Claudio , Thielen Peter , Matus Soledad , Nassif Melissa , Court Felipe , Kiffin Roberta , Martinez Gabriela , Cuervo Ana María , Brown Robert H. , Glimcher Laurie H.
Published: September 2009

Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic reticulum (ER) stress in the disease process via a pathway known as the unfolded protein response (UPR). Here, we investigated the contribution to fALS of X-box-binding protein-1 (XBP-1), a key UPR transcription factor that regulates genes involved in protein folding and quality control. Despite expectations that XBP-1 deficiency would enhance the pathogenesis of mutant SOD1, we observed a dramatic decrease in its toxicity due to an enhanced clearance of mutant SOD1 aggregates by macroautophagy, a cellular pathway involved in lysosome-mediated protein degradation. To validate these observations in vivo, we generated mutant SOD1 transgenic mice with specific deletion of XBP-1 in the nervous system. XBP-1-deficient mice were more resistant to developing disease, correlating with increased levels of autophagy in motoneurons and reduced accumulation of mutant SOD1 aggregates in the spinal cord. Post-mortem spinal cord samples from patients with sporadic ALS and fALS displayed a marked activation of both the UPR and autophagy. Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration.
Epitope mapping of canine distemper virus phosphoprotein by monoclonal antibodies
Authors: Sugai Akihiro , Kooriyama Takanori , Sato Hiroki , Yoneda Misako , Kai Chieko
Published: September 2009

The gene for phosphoprotein (P) of CDV encodes three different proteins, P, V, and C. The P protein is involved in viral gene transcription and replication. In the present study, we produced MAbs against a unique domain of the CDV‐P protein, from aa 232 to 507, and determined their antigenic sites. By immunizing BALB/c mice with the recombinant P protein‐specific fragment, we obtained six MAbs. Competitive binding inhibition assays revealed that they recognized two distinct regions of the P protein. Western blot analysis and immunofluorescence assays using deletion mutants of the unique C‐terminus of the CDV‐P protein revealed that all MAbs recognized a central short region (aa 233–303) of the CDV‐P protein. In addition, linear and conformational epitopes have been determined, and at least four antigenic sites exist in the P protein central region. Furthermore, four of the MAbs were found to react with the P protein of recent Japanese field isolates but not with that of the older CDV strains, including a vaccine strain. Thus, these MAbs could be clinically useful for quick diagnosis during the CDV outbreaks.
Mudstone compaction curves in basin modelling: a study of Mesozoic and Cenozoic Sediments in the northern North Sea
Authors: Marcussen Ø. , Faleide J. I. , Jahren J. , Bjørlykke K.
Published: September 2009

Basin modelling studies are carried out in order to understand the basin evolution and palaeotemperature history of sedimentary basins. The results of basin modelling are sensitive to changes in the physical properties of the rocks in the sedimentary sequences. The rate of basin subsidence depends, to a large extent, on the density of the sedimentary column, which is largely dependent on the porosity and therefore on the rate of compaction. This study has tested the sensitivity of varying porosity/depth curves and related thermal conductivities for the Cenozoic succession along a cross‐section in the northern North Sea basin, offshore Norway. End‐member porosity/depth curves, assuming clay with smectite and kaolinite properties, are compared with a standard compaction curve for shale normally applied to the North Sea. Using these alternate relationships, basin geometries of the Cenozoic succession may vary up to 15% from those predicted using the standard compaction curve. Isostatic subsidence along the cross‐section varies 2.3–4.6% between the two end‐member cases. This leads to a 3–8% difference in tectonic subsidence, with maximum values in the basin centre. Owing to this, the estimated stretching factors vary up to 7.8%, which further gives rise to a maximum difference in heat flow of more than 8.5% in the basin centre. The modelled temperatures for an Upper Jurassic source rock show a deviation of more than 20 °C at present dependent on the thermal conductivity properties in the post‐rift succession. This will influence the modelled hydrocarbon generation history of the basin, which is an essential output from basin modelling analysis. Results from the northern North Sea have shown that varying compaction trends in sediments with varying thermal properties are important parameters to constrain when analysing sedimentary basins.
Shelf edge and shoreline trajectories, a dynamic approach to stratigraphic analysis
Authors: Henriksen Sverre , Hampson Gary J. , Helland‐Hansen William , Johannessen Erik P. , Steel Ron J.
Published: September 2009

The Shelf Edge and Shoreline Trajectories Conference, convened in Tromsø, Norway, during the autumn of 2007, was attended by a group of specialists working in the crossover between industry and academia. This paper introduces the concepts of shelf edge‐ and shoreline‐trajectory analysis, and discusses some of the advantages of applying such concepts in contrast to more traditional sequence stratigraphic analysis. This special issue of Basin Research focuses on how observations of outcrop and subsurface datasets, particularly three‐dimensional (3D) seismic data, may be used as an aid to identify palaeo‐shelf edges and shorelines. Moreover, the approach shows how linking the cross‐sectional path of a shoreline as it migrates (shoreline trajectory) and the pathway taken by the shelf‐edge during the development of a series of accreting clinoforms (shelf‐edge trajectory) to the analysis of sedimentological or seismic facies can improve predictions of lithology distribution. The following 15 papers present well‐documented case studies from a variety of shelf and shelf‐margin settings where these concepts have been applied to depositional systems ranging in age from Permian to Recent. A wide spectrum of data types and methods, including two dimensional and 3D seismic data, well logs and core material as well as high‐resolution biostratigraphy, outcrop studies and modern bathymetric data have been applied in the various papers. Despite the considerable age range of the deposits investigated and the data types used for the studies, all of the authors have converged towards the objective approach of trajectory analysis. However, any analytical method has some uncertainty attached to it, and a discussion of possible pitfalls and sources of error is also a part of this introductory paper. Although this special issue presents some recent advances in the way to conduct stratigraphic analysis, we realise that this is only a further step in an evolving discipline. Development of sequence stratigraphic concepts will continue, and new contributions will evaluate past work as they seek to develop the subject.
Impaired up‐regulation of polo‐like kinase 2 in B‐cell chronic lymphocytic leukaemia lymphocytes resistant to fludarabine and 2‐chlorodeoxyadenosine: a potential marker of defective damage response
Authors: De Viron Emeline , Knoops Laurent , Connerotte Thierry , Smal Caroline , Michaux Lucienne , Saussoy Pascale , Vannuffel Pascal , Beert Eline , Vekemans Marie‐Christiane , Hermans Cédric , Bontemps Françoise , Van Den Neste Eric
Published: September 2009

The functional evaluation of ataxia telangiectasia mutated (ATM) and p53 was recently developed in B‐cell chronic lymphocytic leukaemia (B‐CLL), a disease in which the response to DNA damage is frequently altered. We identified a novel biomarker of chemosensitivity based on the induction of DNA damage by the purine nucleoside analogues (PNA) fludarabine and 2‐chlorodeoxyadenosine (CdA). Using genome‐wide expression profiling, it was observed that, in chemosensitive samples, PNA predominantly increased the expression of p53‐dependent genes, among which PLK2 was the most highly activated at early time points. Conversely, in chemoresistant samples, p53‐dependent and PLK2 responses were abolished. Using a quantitative real time polymerase chain reaction, we confirmed that PNA dose‐ and time‐dependently increased PLK2 expression in chemosensitive but not chemoresistant B‐CLL samples. Analysis of a larger cohort of B‐CLL patients showed that cytotoxicity induced by PNA correlated well with PLK2 mRNA induction. Interestingly, we observed that failure to up‐regulate PLK2 following PNA and chemoresistance were not strictly correlated with structural alterations in the TP53 gene. In conclusion, we propose that testing PLK2 activation after a 24‐h incubation with PNA could be used to investigate the functional integrity of DNA damage‐response pathways in B‐CLL cells, and predict clinical sensitivity to these drugs.
ATG‐saporin‐S6 immunotoxin: a new potent and selective drug to eliminate activated lymphocytes and lymphoma cells
Authors: Polito Letizia , Bortolotti Massimo , Farini Valentina , Pedrazzi Manuela , Tazzari Pier Luigi , Bolognesi Andrea
Published: September 2009

Anti‐thymocyte globulins (ATG) are currently used to prevent graft‐versus‐host disease in haematopoietic stem cell transplants from alternative donors and to treat and prevent acute organ rejection after transplantation. Many recent studies have demonstrated that ATG can also be beneficial in patients with myeloma, lymphoma, leukaemia and myelodysplastic syndrome. This study showed, for the first time, that the cytotoxic effect of ATG can been enhanced by conjugation with saporin‐S6, which is one of the most stable and active type‐1 ribosome‐inactivating proteins. The ATG‐saporin‐S6 immunotoxin showed a strong cytotoxic effect on five lymphoma‐ and leukaemia‐derived cell lines as well as on activated lymphocytes while sparing non‐haematological cell lines. ATG‐saporin‐S6 induced a time‐dependent activation of caspase‐3/7 in RAJI cells. The caspase inhibitor Z‐VAD‐fmk partially rescued the cells that were treated with ATG‐saporin‐S6, suggesting that multiple cell death pathways, some of which are caspase independent, play a role in ATG‐saporin‐S6 toxicity. In our experiments ATG increased the complement‐independent cytotoxicity of activated lymphocytes by a magnitude of 3–5 logs after conjugation. These findings suggest that the ATG‐saporin‐S6 immunotoxin is a promising therapeutic tool for many pathological conditions involving T lymphocytes and T and B neoplastic cells.
Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion‐dependent anaemia and iron overload
Authors: Taher Ali , Cappellini Maria D. , Vichinsky Elliott , Galanello Renzo , Piga Antonio , Lawniczek Tomasz , Clark Joan , Habr Dany , Porter John B.
Published: September 2009

The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion‐dependent anaemias, including β‐thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 μg/l (P < 0·0001) from pre‐dose‐escalation to the time‐of‐analysis; significant decreases were also observed in adult and paediatric patients, as well as β‐thalassaemia patients. The adverse event profile in patients who received deferasirox doses of >30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion‐dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden.
Linkage between bronchial responsiveness to methacholine and gene markers of IL‐4 cytokine gene cluster and T‐cell receptor α/δ gene complex in Korean nuclear families
Authors: Cho S.‐H. , Son J.‐W. , Koh Y.‐Y. , Min K.‐U. , Kim Y.‐Y. , Kim Y.‐K.
Published: September 2009

Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations.

To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor‐β gene (D11S97), IL‐4 cytokine gene cluster (IL‐4R1), and T‐cell receptor α/δ gene complex (D14S50) in Korean nuclear families.

Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib‐pair approach.

The square difference of the slope of the dose–response curve (DRS) between sib‐pairs with two IL‐4R1 identical alleles was smaller than with one or with neither IL‐4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib‐pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL‐4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50.

The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL‐4 cytokine gene cluster and/or T‐cell receptor α/δ gene complex, but the genetic influence of the FcεRI‐β gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families.
Pityrosporum and Candida specific and non‐specific humoral, cellular and cytokine responses in atopic dermatitis patients
Authors: Savolainen J. , Lintu P. , Kosonen J. , Kortekangas‐Savolainen O. , Viander M. , Pène J. , Kalimo K. , Terho E. O. , Bousquet J.
Published: September 2009

Recent cytokine (RT‐PCR, ELISA) analyses of inflammation in atopic dermatitis (AD) have suggested a role for IL‐4, IL‐5 and IFNγ. Pityrosporum ovale and Candida albicans are important allergens in some patients with AD of the seborrhoic head, neck and shoulder region. In AD patients, the saprophytic yeasts induce IgE responses while they usually induce TH1 type responses. The cytokine responses induced by yeasts in AD are sparsely investigated.

To characterize the P. ovale‐ and C. albicans‐specific and non‐specific humoral, lymphoproliferative and cytokine (IL‐2, 4, 5 and IFNγ) responses in AD.

Fifteen AD patients and seven healthy controls (HC) were included. Ficoll‐isolated PBMC were stimulated by PHA and laboratory‐generated extracts of P. ovale and C. albicans. Lymphocyte proliferation was measured by 3H‐thymidine incorporation and cytokine production by sandwich‐ELISAs. The antigen‐specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST.

Pityrosporum ovale‐ and C. albicans‐specific IgE (both P < 0.001) and P. ovale‐induced PBMC proliferation (P < 0.02) were elevated in AD. In general, the IL‐4/IFNγ ratio induced by P. ovale was higher than that induced by C. albicans (P < 0.01). The PHA‐induced IL‐2 (P < 0.05) and IL‐4 responses (P < 0.005), and the C. albicans‐induced IL‐5 response (P < 0.02) and IFNγ response (P < 0.01), were elevated in AD. A network of correlations was seen between serum total and the yeast‐specific IgE, P. ovale‐specific lymphoproliferation, PHA‐induced IL‐2, IL‐4 and IL‐5, and C. albicans‐induced IL‐5.

The cytokine profiles found in this study support the role of TH0 or TH1 cells by the side of TH2 cells in the pathogenesis of atopic dermatitis. Pityrosporum ovale appears to be associated more with IL‐4 responses and C. albicans with IFNγ responses.
Effects of monotherapy with intra‐nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis
Authors: Wilson A. M. , Orr L. C. , Sims E. J. , Lipworth B. J.
Published: September 2009

The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR).

To determine how combined oral mediator blockade compares to monotherapy with intranasal corticosteroid in the treatment of SAR.

Twenty‐two patients with seasonal allergic rhinitis were enrolled in a placebo controlled crossover study comparing 2 weeks therapy of either (a) 200 µg intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 10 mg oral cetirizine once daily (MON/CZ), with a 7–10 day placebo period prior to each treatment period. Domiciliary measures of symptoms and nasal flow were recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and nasal nitric oxide were made after all treatment and placebo periods.

There were significant (P < 0.05) improvements in domiciliary peak nasal flow (l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled placebo (110 (4.0). Both treatments also showed significant improvement in terms of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)), although there was no significant difference between the two active treatments. There were no significant differences between placebo and treatment for rhinomanometry, acoustic rhinometry or nitric oxide.

Both intranasal mometasone furoate as monotherapy and oral cetirizine plus montelukast as cotherapy were equally effective for objective and subjective measures of treatment response in SAR. Domiciliary measurements of symptoms and peak flow were more sensitive than laboratory measurements of rhinomanometry, acoustic rhinometry and nasal nitric oxide.
Intracellular glutathione regulates tumour necrosis factor‐α‐induced p38 MAP kinase activation and RANTES production by human bronchial epithelial cells
Authors: Hashimoto S. , Gon Y. , Matsumoto K. , Takeshita I. , Machino T. , Horie T.
Published: September 2009

RANTES plays an important role in the production of allergic inflammation of the airway through its chemotactic activity for eosinophils. The cellular reduction and oxidation (redox) changes are involved in the activation of p38 mitogen‐activated protein (MAP) kinase and the induction of cytokine expression. It has previously been shown that tumour necrosis factor (TNF)‐MA activates p38 mitogen‐activated protein (MAP) kinase to produce cytokine, including RANTES, that N‐acetylcysteine (NAC) attenuates cytokine production by human bronchial epithelial cells (BECs), and that sensitivity to TNFα is inversely correlated with cellular redox state. However, a role of cellular redox regulated by intracellular glutathione (GSH) in TNFα‐induced p38 MAP kinase activation and p38 MAP kinase‐mediated RANTES production by human BECs has not been determined.

Human BECs were exposed to NAC or buthionine sulfoximine (BSO). TNFα‐induced p38 MAP kinase activation and p38 MAP kinase‐mediated RANTES production by human BECs were then examined in order to clarify these issues.

The results showed that: NAC attenuated TNFα‐induced p38 MAP kinase activation and RANTES production; SB 203580 as the specific inhibitor of p38 MAP kinase activity attenuated TNF‐α‐induced RANTES production; BSO facilitated TNF‐α‐induced p38 MAP kinase activation and RANTES production; SB 203580 attenuated BSO‐mediated facilitation of TNF‐α‐induced RANTES production; and the intracellular GSH increased in NAC‐treated cells, whereas the intracellular GSH was reduced in BSO‐treated cells.

These results indicate that cellular redox regulated by GSH is critical for TNF‐α‐induced p38 MAP kinase activation and p38 MAP kinase‐mediated RANTES production by human BECs.
The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T‐cell allergen‐induced production of IL‐5, IL‐3 and GM‐CSF mRNA and protein
Authors: Powell N. , Till S. J. , Kay A. B. , Corrigan C. J.
Published: September 2009

T‐cell production of eosinophil‐active cytokines (IL‐5, IL‐3, GM‐CSF) is thought to be fundamental to asthma pathogenesis. Inhaled aeroallergens may be one important stimulus for T‐cell cytokine production in asthma.

To compare the potency and efficacy of the topical anti‐asthma glucocorticoids beclomethasone dipropionate (BDP) and fluticasone propionate (FP) in inhibiting allergen‐driven peripheral blood T‐cell proliferation and production of IL‐3, IL‐5 and GM‐CSF mRNA and protein.

Peripheral blood mononuclear cells from six atopic asthmatics sensitized to house dust mite (HDM) were cultured in the presence of HDM and serial dilutions of BDP or FP in vitro. Cellular proliferation (7 days) and culture supernatant cytokine concentrations (6 days) were measured by uptake of tritiated thymidine and ELISA, respectively. Cytokine mRNA expression (24 h) was measured in three subjects using a quantitative PCR technique.

Both BDP and FP inhibited allergen‐induced T‐cell proliferation, expression of IL‐3, IL‐5 and GM‐CSF mRNA, and secretion of the corresponding proteins in a concentration‐dependent fashion. FP was considerably more potent, but not more efficacious, in exerting these actions.

Both BDP and FP have the potential markedly to inhibit allergen‐induced T‐cell production of asthma‐relevant cytokines. This activity is effected at the level of T‐cell proliferation and cytokine gene transcription. These properties may be key features of the anti‐asthma activity of these drugs. The greater potency of FP in vitro may be responsible for its greater clinical potency.
The response of stream fish to local and reach‐scale variation in the occurrence of a benthic aquatic macrophyte
Authors: ARGENTINA JANE E. , FREEMAN MARY C. , FREEMAN BYRON J.
Published: September 2009

1. The aquatic macrophyte Podostemum ceratophyllum has been shown to increase stream productivity, abundance and biomass of benthic invertebrates, and local occurrences of some stream fishes. However, experimental evidence that fishes preferentially associate with Podostemum is lacking, and the value of Podostemum as a predictor of stream fish assemblage composition has not been studied.

2. We conducted two short‐term (2 week), small‐scale (36 m2) experimental manipulations of Podostemum cover in the Conasauga River (Georgia and Tennessee, U.S.), and found higher abundances of benthic insectivorous fishes in patches with augmented (>80%) compared to reduced (7%) Podostemum cover. In an observational study, we quantified associations among percent cover of Podostemum, fish species richness, land cover, shoal length and base‐flow turbidity at 20 randomly selected shoals from a 39‐km reach that spanned a gradient of decreasing forest land cover.

3. Richness of all fish species and of lotic fishes peaked in the centre of the study reach, and richness was weakly correlated with predictor variables. Occupancy models for individual species also indicated that longitudinal position was a strong covariate for 13 of 19 species examined, with little support that Podostemum cover influenced occupancy.

4. Local associations may reflect choices by benthic fishes to utilise Podostemum, whereas downstream decline in fish species richness and Podostemum cover may reflect altered capacity of the system to support native species.
Interactions between fauna and sediment control the breakdown of plant matter in river sediments
Authors: NAVEL SIMON , MERMILLOD‐BLONDIN FLORIAN , MONTUELLE BERNARD , CHAUVET ERIC , SIMON LAURENT , PISCART CHRISTOPHE , MARMONIER PIERRE
Published: September 2009

1. A substantial portion of particulate organic matter (POM) is stored in the sediment of rivers and streams. Leaf litter breakdown as an ecosystem process mediated by microorganisms and invertebrates is well documented in surface waters. In contrast, this process and especially the implication for invertebrates in subsurface environments remain poorly studied.

2. In the hyporheic zone, sediment grain size distribution exerts a strong influence on hydrodynamics and habitability for invertebrates. We expected that the influence of shredders on organic matter breakdown in river sediments would be influenced strongly by the physical structure of the interstitial habitat.

3. To test this hypothesis, the influence of gammarids (shredders commonly encountered in the hyporheos) on degradation of buried leaf litter was measured in experimental systems (slow filtration columns). We manipulated the structure of the sedimentary habitat by addition of sand to a gravel‐based sediment column to reproduce three conditions of accessible pore volume. Ten gammarids were introduced in columns together with litter bags containing alder leaves at a depth of 8 cm in sediment. Leaves were collected after 28 days to determine leaf mass loss and associated microbial activity (fungal biomass, bacterial abundance and glucosidase, xylosidase and aminopeptidase activities).

4. As predicted, the consumption of buried leaf litter by shredders was strongly influenced by the sediment structure. Effective porosity of 35% and 25% allowed the access to buried leaf litter for gammarids, whereas a lower porosity (12%) did not. As a consequence, leaf litter breakdown rates in columns with 35% and 25% effective porosity were twice as high as in the 12% condition. Microbial activity was poorly stimulated by gammarids, suggesting a low microbial contribution to leaf mass loss and a direct effect of gammarids through feeding activity.

5. Our results show that breakdown of POM in subsurface waters depends on the accessibility of food patches to shredders.
Integrating floral scent, pollination ecology and population genetics
Authors: Whitehead Michael R. , Peakall Rod
Published: September 2009

1. Floral scent is a key factor in the attraction of pollinators. Despite this, the role of floral scent in angiosperm speciation and evolution remains poorly understood. Modern population genetic approaches when combined with pollination ecology can open new opportunities for studying the evolutionary role of floral scent.

2. A framework of six hypotheses for the application of population genetic tools to questions about the evolutionary role of floral scent is presented. When floral volatile chemistry is linked to pollinator attraction we can analyse questions such as: Does floral volatile composition reflect plant species boundaries? Can floral scent facilitate or suppress hybridization between taxa? Can the attraction of different pollinators influence plant mating systems and pollen‐mediated gene flow? How is population genetic structure indirectly influenced by floral scent variation?

3. The application of molecular tools in sexually deceptive orchids has confirmed that volatile composition reflects species boundaries, revealed the role of shared floral odour in enabling hybridization, confirmed that the sexual attraction mediated by floral odour has implications for pollen flow and population genetic structure and provided examples of pollinator‐mediated selection on floral scent variation. Interdisciplinary studies to explore links between floral volatile variation, ecology and population genetics are rare in other plant groups.

4. Ideal study systems for future floral scent research that incorporate population genetics will include closely related taxa that are morphologically similar, sympatric and co‐flowering as well as groups that display wide variation in pollination mechanisms and floral volatiles.
Do carnivorous plants use volatiles for attracting prey insects?
Authors: Jürgens Andreas , El‐Sayed Ashraf M. , Suckling D. Max
Published: September 2009

1. Scientists have been fascinated by carnivorous plants for centuries and they have thoroughly investigated how these plants can benefit from insect capture for example through increased growth, earlier flowering, and increased seed production. How prey is actually lured into the traps, however, is less well understood. Trapping prey may be achieved in a random way, for example by camouflaging the traps (hiding them in the surrounding vegetation), so that prey is trapped by accidental landing on the trap leaves or wind drift, or in the other extreme, trapping may involve mimicry of other attractive resources such as fruits or flowers by using specific visual or olfactory signals to attract a specific prey assemblage.

2. We investigated for the first time volatiles of the trapping leaves of carnivorous plant species by dynamic headspace methods. We present data on the venus flytrap Dionaea muscipula, the sundew Drosera binata, and the North American pitcher plants Sarracenia flava, Sarracenia leucophylla, Sarracenia minor, and Sarracenia purpurea. A large number of compounds and relatively high emission rates were found in three of the North American pitcher plants (S. flava, S. leucophylla, and S. minor) with compounds typically found in flowers or fruits. This suggests together with other features (e.g. colour, nectar production) that these traps are possibly flower or fruit mimics. The leaves of S. purpurea, Dionaea muscipula, and Drosera binata emitted much weaker scents with lower numbers of components, consisting mainly of volatiles typically emitted from green leaves.

3. We discuss whether or not the use of volatiles for attracting prey animals is linked with specific trapping mechanisms and whether carnivorous plants can be grouped into specialized ‘olfactory syndromes’.
Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection
Authors: Nishikaku Angela Satie , Ribeiro Luciana Cristina , Molina Raphael Fagnani Sanchez , Albe Bernardo Paulo , Cunha Cláudia da Silva , Burger Eva
Published: September 2009

Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP‐9 and MMP‐2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP‐9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro‐ and active MMP‐9 and active MMP‐2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP‐2 and strong MMP‐9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis‐infected mice had residual lesions with MMP‐9‐positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP‐9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination.
Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride‐induced hepatic injury in the Hanover Wistar rat
Authors: Smyth Rosemary , Munday Michael R. , York Malcolm J. , Clarke Christopher J. , Dare Theo , Turton John A.
Published: September 2009

Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD‐1) is increased in the urine of rats with carbon tetrachloride (CCl4)‐induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD‐1 as a non‐invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl4 at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl4 and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD‐1 in the urine was confirmed by Western blotting with an SOD‐1 antibody. In the dose response study, serum SOD activity was elevated in all CCl4‐treated animals and urinary SOD‐1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl4 dose level (0.80 ml/kg). In the time course study, urinary SOD‐1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD‐1 has potential as a sensitive non‐invasive biomarker of CCl4‐induced hepatocellular injury.
Irinotecan‐induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile
Authors: Stringer Andrea M. , Gibson Rachel J. , Bowen Joanne M. , Logan Richard M. , Ashton Kimberly , Yeoh Ann S.J. , Al‐Dasooqi Noor , Keefe Dorothy M.K.
Published: September 2009

Chemotherapy‐induced diarrhoea is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. Irinotecan is linked with severe mucositis and diarrhoea, the mechanisms of which remain poorly understood. Bacterial β‐glucuronidase is thought to be involved in the metabolism of irinotecan, implicating the intestinal flora. Intestinal mucins may also be implicated in the development of chemotherapy‐induced diarrhoea. Rats were treated with 200 mg/kg of irinotecan and killed at 96, 120 and 144 h. The rats were monitored for diarrhoea. Pathology and immunohistochemical staining was performed. The samples were cultured and faecal DNA was analysed using real‐time polymerase chain reaction. Severe diarrhoea was observed from 72 to 96 h. A decrease in body mass was also observed after treatment. Significant changes in goblet cell numbers (both complete and cavitated cells) were observed in the small and large intestines. Changes in MUC gene expression were observed in the small intestine only. Modifications were observed to the intestinal flora profile, especially Escherichia coli, and an increase in the expression of β‐glucuronidase was detected. In conclusion, irinotecan‐induced diarrhoea may be caused by an increase in some β‐glucuronidase‐producing bacteria, especially E. coli, exacerbating the toxicity of active metabolites. Accelerated mucous secretion and mucin release may also contribute to the delayed onset of diarrhoea.