bluuebunny/crossref_metadata_2025 huggingface dataset:
The analgesic tramadol has minimal effect on gastrointestinal motor function
Authors: Wilder‐Smith Clive H. , Bettiga Andrea
Published: August 2010

AimsThe analgesic tramadol, an opioid agonist and monoaminergic reuptake blocker, has been assumed to interfere less with gastrointestinal motor function than other opioid analgesics, but this has not been specifically investigated. In this study we examined the effect of tramadol on variables of gastrointestinal motor function.MethodsTen healthy volunteers participated in a two‐arm, placebo‐controlled, double‐blind, randomized, cross‐over study comparing tramadol 50 mg and placebo solutions given four times a day for 10 days. Oro‐caecal (lactulose H2‐breath test) and colonic (solid markers) transit times and anal sphincter pressures were measured after 10 days dosing.

ResultsMehan oro‐caecal transit time was 90 min (interquartile range: 75–105) with placebo and 90 min (60–105) with tramadol (not significant). The mehan total colonic transit time increased from 45.6 h (25.2–64.8) with placebo to 58.8 h (50.4–78.0) with tramadol (not significant), which is still within the normal range (< 60 h). Anal sphincter resting pressures were not significantly changed by tramadol compared with placebo.

ConclusionsTramadol has a minor delaying effect on colonic transit, but no effect on upper gastrointestinal transit or gut smooth muscle tone. Tramadol may be a useful analgesic where interference with gut motor function is undesirable.
A placebo controlled study of flumazenil in bronchoscopic procedures
Authors: Williamson Bruce H. , Nolan Peter J. , Tribe Anthony E. , Thompson Philip J.
Published: August 2010

Methods A double‐blind, randomized, placebo controlled trial of the efficacy of flumazenil was conducted in 22 consecutive patients admitted for bronchoscopy. Sedation was induced by inhvidually titrated amounts of intravenous diazepam (mean ± s.d., 15.75 ± 4.4 mg). Post bronchoscopy, patients received up to 1 mg of the benzohazepine antagonist flumazenil (Anexate®) or placebo intravenously. Clinical scores for the degree of sedation, orientation in time and space, co‐operation and anterograde amnesia were used. These, together with three psychometric tests were performed twice prior to bronchoscopy and on eight occasions in the following 24 h. The psychometric tests were: Tapping Test (TT), Simple Reaction Time (SRT) and Critical Flicker Fusion (CFF) and these were carried out using the automated Multipsy test system.

Results The level of co‐operation, orientation in time and space and anterograde amnesia were similar in both groups pre‐and‐post procedure. However compared with the pre‐bronchoscopy assessment, the maximum degree of apparent sedation was significantly less in the flumazenil group in the first 4 h. In support of this, the patients in the flumazenil group also showed a significantly greater proficency with the TT and CFF test post bronchoscopy (P<0.05). There was no difference in the incidence of side effects and flumazenil was well tolerated.

Conclusions In this highly controlled setting, the use of flumazenil (Anexate®) was shown to be safe and effective in aiding recovery from benzodiazepine facilitated bronchoscopy and as such provides an additional level of safety for this procedure.
Short‐term sucralfate administration alters potassium diclofenac absorption in healthy male volunteers
Authors: Júnior José Pedrazzoli , Pierorsi Marcos de Almeida , Muscará Marcelo Nicolás , Dias Heidi Bernadetta , Ferreira da Silva Claudia Maria , Mendet Fabiana Duarte , de Nucci Gilberto
Published: August 2010

Aims Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokmetics of diclofenac.

Methods Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5‐day pre‐treatment with sucralfate (2000 mg twice daily). Blood samples were collected at intervals post‐dose and serum concentrations of diclofenac were determined by reverse‐phase h.p.1.c. Results Pre‐treatment with sucralfate significantly decreased both the AUC(0,8 h) [2265 ng h Ml−1 (geometric mean) (range 1815–2827)vs 1821 ng h ml−’(1295–2562)] and the Cmax [1135 ng ml−1 (geometric mean) (range 898–1436) vs 701 ng ml−1 (501–981)] with no significant delay in absorption [tmax 1.0 h (median) (range 0.5–2.0) vs 1.0 h (0.5‐4.0)l.

Conclusions The short‐tern treatment of healthy male volunteers with sucralfate decreases potassium diclofenac bioavailability. These findings suggest that either an appropriate increase in the diclofenac intake or the use of another gastric mucosa protector must be adopted.
The effect of repeated‐dose activated charcoal on the Pharmacokinetics of sodium valproate in healthy volunteers
Authors: Al‐Shareef A. , Buss D. C. , Shetty H. G. M. , Ali N. , Routledge P. A.
Published: August 2010

AimsWe investigated the effects of repeated‐dose charcoal administered several hours after sodium valproate on the pharmacokinetics of a single dose of the drug in healthy volunteers.

MethodsThe pharmacokinetics of sodium valproate were studied in seven healthy volunteers after administration of a syrup (300 mg) on two occasions, one of which was followed by administration of repeated doses of oral charcoal starting 4 h after the drug up to 32 h (total dose 80 g).

ResultsValproate was rapidly absorbed with maximum concentrations 1 h after administration. The area under the plasma concentration‐time curve to 48 h (AUC (0,48 h)) was 408 ± 114.5 (s.d.)mgl−1h in the control phase and 398 ± 108.6 mgl−1h after charcoal and thet1/2elimination was 20 ± 6.8 h in the control phase, and 22 ± 9.2 h after charcoal (NS).

ConclusionsRepeated‐dose activated charcoal does not appear to enhance the rate of elimination of sodium valproate after therapeutic doses of the drug and any beneficial effect of charcoal in overdose may be to prevent absorption of valproate still present in the gut.
Best practice in therapeutic drug monitoring
Authors: Gross Annette S.
Published: August 2010

It is the goal of Therapeutic Drug Monitoring (TDM) to use drug concentrations to manage a patient’s medication regime and optimise outcome. Limited resources require that drug assays should only be performed when they do contribute to patient management. For this to be the case a therapeutic drug monitoring service has a far greater role than just therapeutic drug measuring. This article describes the roles and functions of a Best Practice TDM service. The features which can and should be strived for in each step of the TDM process—the decision to request a drug level, the biological sample, the request, laboratory measurement, communication of results by the laboratory, clinical interpretation and therapeutic management—are discussed.
Target concentration intervention: beyond Y2K
Authors: Holford Nicholas H. G.
Published: August 2010

Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.
Sulphation of o‐desmethylnaproxen and related compounds by human cytosolic sulfotransferases
Authors: Falany Charles N. , Ström Peter , Swedmark Stellan
Published: August 2010

Naproxen is a nonsteroidal anti‐inflammatory drug widely used as an analgesic and anti‐inflammatory agent. The conjugated forms of naproxen and O‐DMN, its demethylated metabolite, account for 66–92% of naproxen found in human urine. In this study, O‐DMN and structurally related compounds were tested as substrates for seven isoforms of human cytosolic sulfotransferase (SULT). The SULT2 or hydroxysteroid SULT isoforms, SULT2A1 and SULT2B1b, did not show reactivity with any of the compounds. All five SULT1 isoforms were active although there was variability between SULT isoforms and compounds assayed. O‐DMN was sulphated by SULT1A1, SULT1B1 and SULT1E1. All five SULT1 isoforms were capable of conjugating both α‐naphthol and β‐naphthol. Apparent Kmvalues for O‐DMN sulphation were significantly higher than the values for either α‐naphthol or β‐naphthol. SULTs 1A1, 1B1 and 1E1 had Kms for O‐DMN sulphation of 84 µm, 690 µmand 341 µm, respectively. These Kmvalues were 40–1150‐fold higher than the Kmvalues for α‐ and β‐naphthol. The role of the side‐chain in O‐DMN sulphation was studied using a series of structurally related β‐naphthol compounds as substrates for SULT1A1 and SULT1E1. The presence of lipophilic groups increased affinity for both SULT isoforms whereas inclusion of a carboxyl group inhibited activity. These studies indicate that O‐DMN is sulphated by SULT1A1, B1 and 1E1. Because of the high concentrations of SULT1A1 expression in human liver and intestines and its higher affinity for O‐DMN sulphation, SULT1A1 may have a role in the first pass metabolism of O‐DMN.
The NF (Nuclear factor)‐κB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1‐dependent apoptosis in human acute myeloid leukaemia cells
Authors: Dai Yun , Guzman Monica L. , Chen Shuang , Wang Li , Yeung Sin‐Kei , Pei Xin‐Yan , Dent Paul , Jordan Craig T. , Grant Steven
Published: August 2010

Interactions between the nuclear factor (NF)‐κB inhibitor parthenolide and the pan‐histone deacetylase inhibitors (HDACIs) vorinostat and LBH589 were investigated in human acute myeloid leukaemia (AML) cells, including primary AML blasts. Co‐administration of parthenolide blocked HDACI‐mediated phosphorylation/activation of IKK and RelA/p65 in association with increased JNK1 activation in various AML cell types. These events were accompanied by an increase in apoptosis in multiple AML cell lines (e.g. U937, HL‐60, NB4, MV‐4‐11, and MOLM‐13). Significantly, parthenolide also increased HDACI‐mediated cell death in haematopoietic cells transduced with the MLL‐MLLT1 fusion gene, which exhibit certain leukaemia‐initiating cell characteristics, as well as primary AML blasts. Exposure to parthenolide/HDACI regimens clearly inhibited the growth of AML‐colony‐forming units but was relatively sparing toward normal haematopoietic progenitors. Notably, blockade of c‐Jun N‐terminal kinase (JNK) signalling by either pharmacological inhibitors or genetic means (e.g. dominant‐negative JNK1 or JNK1 shRNA) diminished parthenolide/HDACI‐mediated lethality. Moreover, dominant‐negative MKK7, but not dominant‐negative MKK4/SEK1, blocked JNK1 activation and apoptosis induced by parthenolide/HDACI regimens. Together, these findings indicate that parthenolide potentiates HDACI lethality in human AML cells through a process involving NF‐κB inhibition and subsequent MKK7‐dependent activation of the SAPK/JNK pathway. They also raise the possibility that this strategy may target leukaemic progenitor cells.
South Asian immigrants' experience of child protection services: are we recognizing strengths and resilience?
Authors: Maiter Sarah , Stalker Carol
Published: August 2010

Ethno‐racial minority families who come in contact with child protection services face unique challenges that include different ideas about appropriate child rearing practices, possibly different definitions of child maltreatment, the possibility of racial biases and service provision that does not address their particular needs. Ethno‐racial minority immigrants encounter additional barriers to services associated with the challenges of settlement in a new cultural environment. Although considerable research has explored these issues, knowledge of the experiences of ethno‐racial families who have been in contact with child protection is limited. The current paper provides insights from a qualitative study that explored the experiences of one ethno‐racial group (South Asians) in Canada. Findings suggest a variety of reasons that families come into contact with the child protection system, and the characteristics of the sample highlight their difficult financial and employment circumstances. Themes include participants' desire to be better informed about the reasons for child protection involvement and about what they can expect from the worker and the agency. They also identified a wish for services that not only recognize their cultural diversity but also respond to the needs of the whole family. In‐home services were especially appreciated. The findings reveal the resilience and personal agency among participants that can be enhanced through strength‐based approaches to practice. Helping others, establishing community networks and developing needed services were avenues of resilience identified.
Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease
Authors: Dittrich A. M. , Krokowski M. , Meyer H.‐A. , Quarcoo D. , Avagyan A. , Ahrens B. , Kube S. M. , Witzenrath M. , Loddenkemper C. , Cowland J. B. , Hamelmann E.
Published: August 2010

Background
Allergen‐induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways.

Objective
The aim of this study was to identify possible mediators of airway inflammation (AI) in a model of allergic AI via microarray comparisons and to analyse one of these mediators, Lipocalin2 (Lcn2), for its role in a murine model of allergic airway disease.

Methods
Gene microarrays were used to identify genes with at least a twofold increase in gene expression in the lungs of two separate mouse strains with high and low allergic susceptibility, respectively. Validation of mRNA data was obtained by Western blotting, followed by functional analysis of one of the identified genes, Lcn2, in mice with targeted disruption of specific gene expression. Epithelial cell cultures were undertaken to define induction requirements and possible mechanistic basis of the results observed in the Lcn2 knock‐out mice.

Results
Lcn2 was up‐regulated upon allergen sensitization and airway challenges in lung tissues of both mouse strains and retraced on the protein level in bronchoalveolar lavage fluids. Functional relevance was assessed in mice genetically deficient for Lcn2, which showed enhanced airway resistance and increased AI associated with decreased apoptosis of lung inflammatory cells, compared with wild‐type controls. Similarly, application of Lcn2‐blocking antibodies before airway challenges resulted in increased inflammation and reduced apoptosis.

Conclusion
These data indicate a protective role for Lcn2 in allergic airway disease, suggesting a pro‐apoptotic effect as the underlying mechanism.

Cite this as: A. M. Dittrich, M. Krokowski, H.‐A. Meyer, D. Quarcoo, A. Avagyan, B. Ahrens, S. M. Kube, M. Witzenrath, C. Loddenkemper, J. B. Cowland and E. Hamelmann, Clinical & Experimental Allergy, 2010 (40) 1689–1700.
T cell inflammatory response, Foxp3 and TNFRS18‐L regulation of peripheral blood mononuclear cells from patients with nasal polyps‐asthma after staphylococcal superantigen stimulation
Authors: Pérez Novo C. A. , Jedrzejczak‐Czechowicz M. , Lewandowska‐Polak A. , Claeys C. , Holtappels G. , Van Cauwenberge P. , Kowalski M. L. , Bachert C.
Published: August 2010

Cite this as: C. A. Pérez Novo, M. Jedrzejczak‐Czechowicz, A. Lewandowska‐Polak, C. Claeys, G. Holtappels, P. Van Cauwenberge, M. L. Kowalski and C. Bachert, Clinical & Experimental Allergy, 2010 (40) 1323–1332.

Background
Staphylococcal superantigens may modulate airway inflammatory disease.

Objective
We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity.

Methods
Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP‐ATA) and five with aspirin‐induced asthma (NP‐AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of TH1/TH2 cytokines was assessed by Cytometric Bead‐Array. Foxp3 and TNFRS18‐L expression were analysed by qPCR and flow cytometry.

Results
After 4 and 18 h, SEB significantly increased IFN‐gamma, IL‐4, TNF‐alpha, IL‐5 and IL‐2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP‐asthma groups. Incubation with SEB for 4 h induced a limited up‐regulation of Foxp3 in NP‐AIA patients, which was switched off consecutively. Foxp3 was significantly up‐regulated in the control group after 18 h, but not in the NP‐asthmatic groups. In parallel, TNFRS18‐L mRNA significantly increased after 18 h in the NP‐asthma groups compared with control subjects. This molecule was highly expressed in CD11c+CD14+ cells and its levels increased after 18 and 24 h culture in the NP‐asthma patients.

Conclusion
SEB induces both TH1 and TH2 pro‐inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP‐asthmatic patients and/or to the up‐regulation of TNFRS18‐L on monocytes/dendritic cell precursors.
Characterization of peach thaumatin‐like proteins and their identification as major peach allergens
Authors: Palacín A. , Tordesillas L. , Gamboa P. , Sanchez‐Monge R. , Cuesta‐Herranz J. , Sanz M. L. , Barber D. , Salcedo G. , Díaz‐Perales A.
Published: August 2010

Background
Peach is the most important fruit related to food allergy in the Mediterranean area. Pru p 3, its lipid transfer protein, has been described as the principal allergen responsible for cross‐reactivities with other foods and pollen and the severity of clinical symptoms. However, the involvement of other allergenic families cannot be ruled out. Thaumatin‐like proteins (TLPs) have been described as food allergen in several fruits, such as apple, cherry, kiwi and banana, and pollen.

Objective
To identify members of the TLP family in peach fruit and to characterize putative allergens.

Methods
Through two‐dimensional (2D) electrophoresis of peach extract and immunodetections with a pool of peach‐allergic patients, IgE‐binding spots were identified and the corresponding proteins purified and characterized as allergens by in vitro and in vivo assays.

Three isoforms, belonging to the TLP family, were purified by different chromatographic systems and characterized by N‐terminal amino acid sequences, molecular weight determination (MALDI) and enzymatic activity analysis (β‐1,3‐gluconase test and inhibition growth of fungi). In the same way, their IgE‐binding capacity and allergenic activity were tested by ELISA assays, basophil activation tests and skin prick tests (SPT).

Results
Two peach‐TLPs, Pru p 2.0101 and Pru p 2.0201, were identified as IgE‐binding spots by 2D electrophoresis. Another peach‐TLP, Pru p 2.0301, was cloned and produced as recombinant protein in a yeast system. The three isoforms were purified and characterized as TLPs by immunoblotting with anti‐chestnut TLP antibodies and anti‐plant N‐asparagine complex glycan (anti‐cross‐reactive carbohydrate determinant). All of them showed β‐1,3‐glucanase activity and inhibition of fungal growth. The three TLPs were recognized by around 50% of the sera from 31 patients analysed in ELISA experiments. All three gave a positive response to an SPT and/or in basophil activation experiments.

Conclusion
Three isoforms, belonging to the TLP family, were identified in peach as principal allergens. Their prevalence, observed in in vitro, ex vivo and in vivo analyses, suggests that they are important allergens and should therefore be included in the routine diagnosis of peach allergy, at least in the Mediterranean area.

Cite this as: A. Palacín, L. Tordesillas, P. Gamboa, R. Sanchez‐Monge, J. Cuesta‐Herranz, M. L. Sanz, D. Barber, G. Salcedo and A. Díaz‐Perales, Clinical & Experimental Allergy, 2010 (40) 1422–1430.
Preferential activation of peripheral blood Vγ9+γ/δ T cells by group A, B and C but not group D or F streptococci
Authors: BENDER A , KABELITZ D
Published: August 2010

Previous studies have established that inactivated mycobacteria are potent and selective activators of Vγ9+/Vδ2+ human γ/δ T cells. Here we have analysed the proliferative response of human γ/δ T cells to five serologically distinct groups of streptococci. While heat-inactivated streptococci of all five serogroups tested (A, B. C, D and F) induced a strong proliferative response in peripheral blood mononuclear cells (PBMC), only groups A, B and C elicited a selective activation of Vγ9+γ/δ T cells in 10 (serogroup B) or 11 (serogroups A and C) of 11 tested healthy individuals. In striking contrast, groups D and F streptococci failed to activate γ/δ T cells in nine of 11 donors and induced only a weak γ/δ T cell response in two additional individuals. Depletion of Vγ9+ T cells before culture completely eliminated all γ/δ T cell responses to streptococci. These data indicate that groups A, B and C (but not D or F) streptococci can be included in the growing list of selective ligands for Vγ9+/Vδ2+ human γ/δ T cells.
Cellular responses to human chondrocytes: absence of allogeneic responses in the presence of HLA-DR and ICAM-1
Authors: JOBANPUTRA P , CORRIGALL V , KINGSLEY G , PANAYI G
Published: August 2010

To assess the accessory cell function of human articular chondrocytes, we assessed the ability of human chondrocytes to stimulate allogeneic peripheral blood mononuclear cells (PBMC) and to support phytohacmagglutinin (PHA)-induced proliferation of highly purified T cells. We also examined the surface expression of HLA-DR and ICAM-1 on the chondrocytes both unstimulated and stimulated with cytokines in vitro. Chondrocytes failed to stimulate allogeneic PBMC despite the constitutive expression of MHC class I molecules and the cytokine-induced expression of class II molecules but were able to support T cell proliferation to PHA, IFN-γ and to a limited extent, IL-1β, induced class II expression on chondrocytes. ICAM-1 was present on 94–99% of freshly isolated cells; this declined with culture (17–59%; P<0·005) but was readily induced by IFN-γ, IL-1β, and tumour necrosis factor-alpha. Alloreactivity and, presumably, autoreactivity to chondrocytes requires factors in addition to the surface expression of DR and ICAM-1. However the presence of these molecules suggests a capacity for cell-cell interactions in inflammatory sites such as the cartilage pannus junction.
Significance of IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB)
Authors: Kadota J , Matsubara Y , Ishimatsu Y , Ashida M , Abe K , Shirai R , Iida K , Kawakami K , Taniguchi H , Fujii T , Kaseda M , Kawamoto S , Kohno S
Published: August 2010

We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The number of neutrophils in BALF obtained from DPB patients was significantly higher than that of healthy volunteers. Treatment with erythromycin (600 mg/day for 12.9 γδ+9.5 months (mean γδ+s.d.)) significantly reduced the total number of cells and neutrophils in the airway, and significantly improved pulmonary function tests. The levels of IL-1β and IL-8 were significantly higher in DPB compared with healthy volunteers (P < 0.05, P < 0.05, respectively). IL-1 Ra in patients is considered to have a weak inhibitory activity for IL-1β, with approximately five-fold concentration of IL-1β compared with that in healthy volunteers (approx. nine-fold concentration of IL-1β). Erythromycin therapy significantly reduced these cytokines to levels comparable to those of healthy volunteers, and produced a trend toward reduction in the level of IL-1Ra in BALF. The level of IL-1β correlated significantly with the concentration of neutrophils in BALF (r= 0.72, P < 0.01), as well as with the level of IL-1Ra (r= 0.688, P < 0.05) and IL-8 (r= 0.653, P < 0.05). A nearly significant or significant correlation was observed between the concentration of neutrophils and levels of IL-1Ra or IL-8 in BALF (r= 0.526, P= 0.053 or r= 0.776, P < 0.01, respectively). There was also a significant relationship between FEV, and the concentration of neutrophils in BALF (r= 0.524, P < 0.05). Our results suggest that the relative amounts of IL-1β and IL-1Ra or IL-8 may contribute, at least in part, to the neutrophil-mediated chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cycle between the cytokine network and neutrophil accumulation, with resultant reduction of neutrophil-mediated inflammatory response.
Biochemical analysis and immunogenicity ofLeishmania majoramastigote fractions in cutaneous leishmaniasis
Authors: RAFATI S , COUTY-JOUVE S , ALIMOHAMMADIAN M H , LOUIS J A
Published: August 2010

Soluble Leishmania antigen (SLA) from both developmental stages of L. major (L. major MRHO/IR/75/ ER) were prepared. Three and five subfractions of SLA from amastigote and promastigote were obtained by fast protein liquid chromatography (FPLC), respectively. Biochemical analyses and comparison of amastigote and promastigote SLA were done. The biochemical analyses revealed that the first fraction of L. major amastigote possesses a distinct band on its electrophoretic mobility pattern corresponding to a position of 24 kD, and it has enzymatic activity with characteristics of a cysteine proteinase. The isolated fractions of amastigote were tested for induction of proliferation, interferon-gamma (IFN-γ) and IL-4 production in cultures of peripheral blood mononuclear cells (PBMC) from individuals who had recovered and also chronic patients of cutaneous leishmaniasis caused by L. major. The cells of recovered individuals compared with chronic cases proliferated profoundly in response to the first fraction of amastigote SLA. In all recovered individuals, the IFN-γ, but not IL-4, was secreted in response to stimulation with the first fraction of amastigote SLA. In chronic cutaneous leishmaniasis, IFN-γ was infrequently observed in response to stimulation by all three fractions of amastigote SLA, but secretion of IL-4 was observed. These data indicate that first fraction of amastigote SLA is a strong inducer of primed human immune response to L. major, and may have a protective function.
Evaluation of PG‐M3 antibody in the diagnosis of acute promyelocytic leukaemia
Authors: Gupta Sanjeev Kumar , Sazawal Sudha , Mahapatra Manoranjan , Saxena Renu
Published: August 2010

Eur J Clin Invest 2010; 40 (10): 960–962

Background & objectives  Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid leukaemia (AML) characterized by a reciprocal translocation, t(15;17) and a high incidence of life‐threatening coagulopathy. APL diagnosis is considered a medical emergency. As reverse transcription‐polymerase chain reaction (RT‐PCR) for PML‐RARα fusion oncoprotein is time consuming, there is a need for a rapid and accurate diagnostic test for APL. This study evaluates the role of PG‐M3 monoclonal antibody using immunofluorescence (IF) in the early diagnosis of APL.

Materials and Methods  Thirty‐six new untreated APL cases diagnosed with RT‐PCR for PML‐RARα as the gold standard and 38 non‐APL controls (28 non‐APL AMLs and 10 non‐leukaemic samples) were evaluated by routine morphology and cytochemistry, RT‐PCR and IF using PG‐M3 monoclonal antibody.

Results  Using IF, 34 of 36 (94·4%) APL cases showed a microgranular pattern suggestive of APL and two cases (5·6%) showed a speckled pattern typical of wild‐type PML protein (False negative). By comparison, two of 28 (7·1%) non‐APL AMLs showed microgranular pattern (false positive). Hence, IF as a diagnostic test for APL resulted in a sensitivity of 94·4%, specificity of 92·9% and positive and negative predictive values of 94·4% and 92·9% respectively. All 10 non‐leukaemic samples showed a speckled pattern.

Conclusions  IF using PG‐M3 antibodies can be used as a rapid (takes 2 h), cheap, sensitive and specific method to identify APL. It can be a useful adjunct for diagnosis of APL especially if facilities for RT‐PCR are not available, particularly in resource‐limited settings.
Lipid assessment, metabolic syndrome and coronary heart disease risk
Authors: Arsenault Benoit J. , Després Jean‐Pierre , Stroes Erik S. G. , Wareham Nicholas J. , Kastelein John J. P. , Khaw Kay‐Tee , Boekholdt S. Matthijs
Published: August 2010

Eur J Clin Invest 2010; 40 (12): 1081–1093

Background  Although the total to high‐density lipoprotein cholesterol ratio (TC/HDL‐C) has been used for decades to identify individuals at risk for coronary heart disease (CHD), apolipoprotein‐based (apolipoprotein B/apolipoprotein A‐I [apoB/apoA‐I]) and nuclear magnetic resonance spectroscopy (NMR)‐based lipoprotein concentrations (low‐density lipoproteinNMR/high‐density lipoproteinNMR [LDLNMR/HDLNMR]) may also be useful for CHD risk stratification.

Materials and methods  In a case–control study conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)‐Norfolk study population, 870 individuals who developed CHD during a 6‐year follow‐up were matched to 1659 controls on the basis of gender, age and enrolment time. LDLNMR and HDLNMR were measured by proton NMR spectroscopy.

Results  After adjusting for traditional CHD risk factors, men in the top quintile of the various lipoprotein ratios proved to be at increased CHD risk (OR = 2·59 [95% IC, 1·76–3·83] for TC/HDL‐C ratio, 2·59 [1·75–3·83] for apoB/apoA‐I ratio and 2·78 [1·86–4·17] for LDLNMR/HDLNMR ratio) compared with men in the bottom quintile. Similar associations were observed in women (OR = 2·86 [1·71–4·80] for TC/HDL‐C ratio, 2·94 [1·74–4·97] for apoB/apoA‐I ratio and 2·03 [1·21–3·43] for LDLNMR/HDLNMR ratio). Compared with participants with only one component of the metabolic syndrome, those who had five had an increased TC/HDL‐C ratio (73·0% and 80·4% in men and women respectively), apoB/apoA‐I ratio (58·0% and 62·9% in men and women respectively) and for LDLNMR/HDLNMR ratio (52·6% and 54·1% in men and women respectively).

Conclusion  In this European study population, the TC/HDL‐C, apoB/apoA‐I and LDLNMR/HDLNMR ratios were similarly associated with components of the metabolic syndrome and CHD risk.
Penetration resistance of gypsiferous horizons
Authors: POCH R. M. , VERPLANCKE H.
Published: August 2010

To assess the importance and the possible causes of penetration resistance of horizons with gypsum, 20 horizons in seven irrigated profiles were studied. Gypsum contents ranged from 0 to 900 g kg−1. Penetrometer tests were performed on undisturbed soil cores by means of a needle penetrometer at different matric potentials. The increase of penetration resistance on drying was caused by changes in the effective stress of the soils, calculated from their soil water characteristic curves. Multiple regression tests showed that besides water content and bulk density, gypsum content was positively correlated with penetration resistance. It seems that in the soils studied the increase of penetration resistance caused by gypsum is due to the growth of gypsum crystals in pre‐existing pores, which reduces the volume of regular and continuous voids necessary for root growth.
The origin and loss of fractal scaling in simulated soil aggregates
Authors: CRAWFORD J. W. , VERRALL S. , YOUNG I. M.
Published: August 2010

A growing body of evidence supports the use of fractals to approximate the heterogeneous structure of soil. Fractal models of transport processes in soil indicate that the fractal dimension and the upper limit to fractal scaling (denoted ξ) determine flow rates and scaling properties. A two‐dimensional Monte Carlo simulation of soil aggregation is used to identify the key processes which may lead to fractal‐like scaling in the soil matrix. A bonding law is developed which parameterizes the relative importance of chemical bonding to binding by microbial by‐products and fungi. We investigate the sensitivity of the fractal dimension and ξ to the nature of the bonding law, and to aggregate fragmentation, initial particle size distribution and mechanical restructuring. Fractal‐like structures result from the aggregation process. However, the measured fractal dimension is insensitive to the detailed form of the bonding law. The factor that most sensitively influences the fractal dimension is found to be mechanical restructuring such as would arise from the action of roots, soil fauna and natural weathering. By contrast, ξ is most sensitive to the bonding law. The results suggest that the fractal dimension and characteristic diameter of aggregates should be uncorrelated, and that increased binding by microbial by‐products and fungi should produce larger, less dense, aggregates.
Trivalent metal (Cr, Y, Rh, La, Pr, Gd) sorption in two acid soils and its consequences for bioremediation
Authors: JONES D. L.
Published: August 2010

The recent addition of trivalent metals to soil and their subsequent movement within the biosphere are of concern. For this reason, the sorption of chromium (Cr), yttrium (Y). rhodium (Rh), lanthanum (La), praseodymium (Pr) and gadolinium (Gd) in two contrasting acid soils has been determined. Except for Rh, the sorption of the other trivalent metals conformed well to the Langmuir equation with derived sorption parameters similar for all the trivalent species tested. Calculation of the buffer powers indicated that under both small (0·01 mmol kg−1) and large (1 mmol kg−1) trivalent metal soil loadings > 99·5% of the metals will be associated with the exchange phase with small quantities present in the bulk soil solution (<0·5%). It seems that the slight availability of metals within the bulk soil solution will slow the rate of trivalent metal bioremediation of contaminated sites.
Spatial distribution of phytoplankton in Lake Baikal, Spring 1991
Authors: BONDARENKO N.A. , GUSELNIKOVA N.E. , LOGACHEVA N.F. , POMAZKINA G.V.
Published: August 2010

Studies carried out in Lake Baikal in late spring (late May‐early June) 1991 showed marked differences in the species composition and abundance of phytoplankton in different regions of the lake. The south and north basins were characterized by small forms of algae. The middle basin, Maloe More and the shallow waters of the Selenga had species with large cells including Aulacoseira islandica subsp. helvetica, Dinobryon cylindricum and D. divergens.

Areas of high biomass were correlated with shallow waters and river inputs. This was especially apparent in the region of the Selenga delta. The vertical distribution of phytoplankton indicated the non‐synchronous start of the spring homothermy throughout the lake. Phytoplankton were concentrated in the upper 100 m layer with subsurface maxima resulting from the sinking of large algae.

The concentration of phytoplankton biomass in general at this time characterized the lake as moderately productive.
Light limitation of phytoplankton development in an oligotrophic lake ‐ Loch Ness, Scotland
Authors: JONES R.I. , YOUNG J.M. , HARTLEY A.M. , BAILEY‐WATTS A.E.
Published: August 2010

The underwater light climate in Loch Ness is described in terms of mixing depth (Zm) and depth of the euphoric zone (Zeu). During periods of complete mixing, Zm equates with the mean depth of the loch (132 m), but even during summer stratification the morphometry of the loch and the strong prevailing winds produce a deep thermocline and an epilimnetic mixed layer of about 30 m or greater. Hence, throughout the year the quotient Zm/Zeu is exceptionally high and the underwater light climate particularly unfavourable for phytoplankton production and growth.

Phytoplankton biomass expressed as chlorophyll a is very low in Loch Ness, with a late summer maximum of less than 1.5 mg chlorophyll a m‐3 in the upper 30 m of the water column. This low biomass and the resulting very low photosynthetic carbon fixation within the water column are evidence that a severe restraint is imposed on the rate at which phytoplankton can grow in the loch.

The chlorophyll a content per unit of phytoplankton biovolume and the maximum, light‐saturated specific rate of photosynthesis are both parameters which might be influenced by the light climate under which the phytoplankton have grown. However, values obtained from Loch Ness for both chlorophyll a content (mean 0.0045 mg mm‐3) and maximum photosynthetic rate (1–4 mg C mg Chla‐1 h‐1) are within the range reported from other lakes.

Laboratory bioassays with the natural phytoplankton community from Loch Ness on two occasions in late summer when the light climate in the loch is at its most favourable, suggest that even then limitation of phytoplankton growth is finely balanced between light and phosphorus limitation. Hence, for most of the year, when the light climate is less favourable, phytoplankton growth will be light limited.

Quotients relating mean annual algal biomass as chlorophyll a (c. 0.5 mg Chla m‐3) and the probable annual specific areal loading of total phosphorus (0.4–1.7 g TP m‐2 yr‐1) suggest that the efficiency with which phytoplankton is produced in Loch Ness per unit of TP loading is extremely low when compared with values from other Scottish lochs for which such an index has been calculated. This apparent inefficiency can be attributed to suppression of photosynthetic productivity in the water column due to the unfavourable underwater light climate.

These several independent sources of evidence lead to the conclusion that phytoplankton development in Loch Ness is constrained by light rather than by nutrients. Loch Ness thus appears to provide an exception to the generally accepted paradigm that phytoplankton development in lakes of an oligotrophic character is constrained by nutrient availability.
The influence of humic substances on the molecular weight distributions of phosphate and iron in epilimnetic lake waters
Authors: Shaw Peter J. , Jones Roger I. , De Haan Henk
Published: August 2010

1. The influence of humic substances on the association of free inorganic iron and phosphate with material of larger molecular weight was investigated in epilimnetic samples from two humus‐rich lakes of contrasting ionic strength. After modification of the molecular weight distribution of the humic substances in the samples using dialysis and ultrafiltration, the molecular weight distribution of added radioisotopes ( Fe3+ and

PO43−) was assessed using gel filtration chromatography.  2. The association of

Fe3+ and

PO43− with larger molecular weight fractions (>50 000 and 10 000–50 000 Da) was not in general related to the quantity of humic substances of the same molecular weight in the samples. However, the proportions of

Fe3+ and

PO43− observed in higher molecular weight peaks were strongly correlated to the quantity of humic substances of the same molecular weight in (a) the 10 000–50 000 Da peak in the sample of low ionic strength at pH 5.5 and pH 7.0, and (b) the> 50 000 Da peak in the sample of higher ionic strength at pH 4.0.  3. It was concluded that humic substances promote the association of

Fe3+ and

PO43− with higher molecular weight fractions primarily by acting as peptizing agents for inorganic colloids containing Fe and P. Association of

Fe3+ and

PO43− with material of higher molecular weight via the formation of humic substance‐Fe3+–PO43− complexes was identified but only at specific pH and within specific molecular weight ranges for each of the epilimnetic lake water samples studied.
Differences in endozoochorous dispersal between aquatic plant species, with reference to plant population persistence in rivers
Authors: POLLUX B. J. A. , SANTAMARIA L. , OUBORG N. J.
Published: August 2010

Summary 1. In river ecosystems, populations are continuously subjected to unidirectional downstream currents resulting in a downstream movement of populations. To ensure long‐term population persistence in rivers, organisms must have a mechanism for upstream dispersal, which allows them to re‐colonise upstream areas.

2. In this study we assessed differences in the potential for endozoochorous seed dispersal of Sparganium emersum and Sagittaria sagittifolia, two aquatic plant species with different seed morphologies, by mallard (Anas platyrhynchos) and teal (Anas crecca), two duck species with different body weights.

3. We found no significant differences in seed retrieval (the proportion of ingested seeds retrieved after gut passage) and seed retention time (time between seed ingestion and retrieval), between mallard and teal, despite the difference in body weights. We did find a significantly higher germination (%) over retention time of S. emersum seeds retrieved from teal compared with mallard, most likely related to a more efficient removal of the seed coat during passage through the gut of teal.

4. There were large differences between S. emersum versus S. sagittifolia in: (i) seed retrieval (22.65 ± 20.8% versus 1.60 ± 2.4%, respectively); (ii) seed retention time in duck gut, with a maximum of 60 h versus 12 h; (iii) the effect of gut passage on seed germination, with an increase of approximately 35% versus a decrease of 25%; and (iv) the effect of gut passage on seed germination rate, with an acceleration of 10 days versus a delay of 3 days on average. The results show that S. emersum has a higher potential for endozoochorous dispersal by ducks and postdispersal establishment than S. sagittifolia.

5. We propose that, in rivers, bird‐mediated seed dispersal may promote re‐colonisation of upstream areas, enabling long‐term plant population persistence.
Thermal adaptation of Arctic charr: experimental studies of growth in eleven charr populations from Sweden, Norway and Britain
Authors: LARSSON S. , FORSETH T. , BERGLUND I. , JENSEN A. J. , NÄSLUND I. , ELLIOTT J. M. , JONSSON B.
Published: August 2010

1. Experimental growth data for Arctic charr (Salvelinus alpinusL.), all fed on excess rations, from 11 European watercourses between 54 and 70°N were analysed and fitted to a new general growth model for fish. The model was validated by comparing its predictions with the growth rate of charr in the wild.

2. Growth performance varied among populations, mainly because of variation in the maximum growth potential, whereas the thermal response curves were similar. The estimated lower and upper temperatures for growth varied between −1.7 to 5.3 and 20.8–23.2 °C, respectively, while maximum growth occurred between 14.4 and 17.2 °C.

3. There was no geographical or climatic trend in growth performance among populations and therefore no indication of thermal adaptation. The growth potential of charr from different populations correlated positively with fish body length at maturity and maximum weight in the wild. Charr from populations including large piscivorous fish had higher growth rates under standardised conditions than those from populations feeding on zoobenthos or zooplankton. Therefore, the adaptive variation in growth potential was related to life‐history characteristics and diet, rather than to thermal conditions.
Tangled webs: reciprocal flows of invertebrate prey link streams and riparian zones
Authors: BAXTER COLDEN V. , FAUSCH KURT D. , CARL SAUNDERS W.
Published: August 2010

1. Streams and their adjacent riparian zones are closely linked by reciprocal flows of invertebrate prey. We review characteristics of these prey subsidies and their strong direct and indirect effects on consumers and recipient food webs.

2. Fluxes of terrestrial invertebrates to streams can provide up to half the annual energy budget for drift‐feeding fishes such as salmonids, despite the fact that input occurs principally in summer. Inputs appear highest from closed‐canopy riparian zones with deciduous vegetation and vary markedly with invertebrate phenology and weather. Two field experiments that manipulated this prey subsidy showed that it affected both foraging and local abundance of stream fishes.

3. Emergence of adult insects from streams can constitute a substantial export of benthic production to riparian consumers such as birds, bats, lizards, and spiders, and contributes 25–100% of the energy or carbon to such species. Emergence typically peaks in early summer in the temperate zone, but also provides a low‐level flux from autumn to spring in ice‐free streams. This flux varies with in‐stream productivity, and declines exponentially with distance from the stream edge. Some predators aggregate near streams and forage on these prey during periods of peak emergence, whereas others rely on the lower subsidy from autumn through spring when terrestrial prey are scarce. Several field experiments that manipulated this subsidy showed that it affected the short‐term behaviour, growth, and abundance of terrestrial consumers.

4. Reciprocal prey subsidies also have important indirect effects on both stream and riparian food webs. Theory predicts that allochthonous prey should increase density of subsidised predators, thereby increasing predation on in situ prey and causing a negative indirect effect via apparent competition. However, short‐term experiments have produced either positive or negative indirect effects. These contrasting results may be due to characteristics of the subsidies and individual consumers, but could also result from differences in experimental designs.

5. New study approaches are needed to better determine the direct and indirect effects of reciprocal prey subsidies. Experiments coupled with comparative research will be required to measure their effects on individual consumer fitness and population demographics. Future work should investigate whether reciprocal prey fluxes stabilise linked stream–riparian ecosystems, explore how landscape context affects the magnitude and importance of subsidies, and determine how impacts of human disturbance can propagate between streams and riparian zones via these trophic linkages. Study of these reciprocal connections is helping to define a more holistic perspective of catchments, and has the potential to shape new directions for ecology in general.
The pulmonary plasma cell/histiocytoma complex
Authors: SPENCER H.
Published: August 2010

Twenty‐seven pulmonary lesions have been reviewed both clinically and pathologically mainly by light microscopy. Almost all the lesions have shown features which were predominantly those associated with either a plasma cell granuloma or a histiocytoma. Both conditions arise from a common chronic inflammatory origin and form one disease complex. In almost every instance the lesions show some features characteristic of the other. In two malignant change had occurred. The light microscopic and electron microscopic characteristics of this complex of lung lesions are described. A possible aetiological cause is suggested. The many names that have been given to this group of pulmonary lesions in the past have led to confusion and failure to recognize their inflammatory nature.
Unusual malignant neuroectodermal tumours of the ovary—case report and literature review
Authors: BURKE MARGARET , BEILBY J.O.W.
Published: August 2010

A malignant tumour of ovary incorporating neuroectodermal and mesenchymal elements is presented together with a review of the recent literature. Comparison is made with analogous neoplasia known to arise at other sites. The possible histogenesis and management are discussed.
Inflammatory fibrous histiocytoma of the penis
Authors: FLETCHER C.D.M. , LOWE D.
Published: August 2010

A 62‐year‐old man presented with a penile mass which was diagnosed histologically as an inflammatory fibrous histiocytoma. The predominant inflammatory cells in the tumour were eosinophils. The tumour regressed after radiotherapy but recurred eight months later, when it showed very few inflammatory cells. At no time did this patient have an elevated white cell count. This tumour has not previously been reported on the penis, nor have eosinophils been described as the principal inflammatory cell in these tumours.