bluuebunny/crossref_metadata_2025 huggingface dataset:
Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates
Authors: Winklbaur Bernadette , Kopf Nina , Ebner Nina , Jung Erika , Thau Kenneth , Fischer Gabriele
Published: August 2008

Aims Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence‐based recommendations for consideration as guidance in the management of opioid‐dependent pregnant women and infants.

Methods PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity.

Results Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi‐disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes.

Recommendations Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication.

Conclusion Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.
Development of the treatment outcomes profile
Authors: Marsden John , Farrell Michael , Bradbury Colin , Dale‐Perera Annette , Eastwood Brian , Roxburgh Malcolm , Taylor Steve
Published: August 2008

Aim  To develop the Treatment Outcomes Profile (TOP), a new instrument for monitoring substance misuse treatment.

Design  Prospective cohort, psychometric evaluation with 7‐day retest and 1‐month follow‐up to assess inter‐rater reliability, concurrent, discriminant and construct validity, and change sensitivity.

Participants  A sample of 1021 service users, aged 16–62 years. Recruitment from 63 treatment agencies in England, collectively providing opioid substitution treatment, psychosocial interventions, in‐patient detoxification and residential rehabilitation.

Measurements  Thirty‐eight frequency, rating scale and period prevalence measures, with 28‐day recall, across substance use, health, crime and social functioning domains, administered as personal interview by 163 treatment keyworkers.

Findings  Twenty outcome measures met inter‐rater reliability criteria: days used alcohol, opioids, crack cocaine, cocaine powder, amphetamines, cannabis and one other named substance; days injected and period prevalence of direct or indirect needle/syringe sharing; subjective rating of physical and psychological health; days committed shop theft and drug selling, period prevalence of vehicle, property, fraud/forgery and assault/violence offences; rating of quality of life; days worked and attended for education/training; and period prevalence of acute housing problems and risk of eviction. Intraclass correlation coefficients for scale measures and Cohen's kappa for dichotomous measures reached or exceeded 0.75 and 0.61, respectively. There were satisfactory validity assessments and change sensitivity of scale items judged by effect size and smallest detectable difference. The TOP clinical tool contains an additional 10 items for individual treatment planning and review.

Conclusions  The TOP is a reliable and valid 20‐item instrument for treatment outcomes monitoring.
Von Willebrand factor propeptide makes it easy to identify the shorter Von Willebrand factor survival in patients with type 1 and type Vicenza von Willebrand disease
Authors: Sztukowska M. , Gallinaro L. , Cattini M. G. , Pontara E. , Sartorello F. , Daidone V. , Padrini R. , Pagnan A. , Casonato A.
Published: August 2008

Reduced von Willebrand factor (VWF) half‐life has been suggested as a new pathogenic mechanism in von Willebrand disease (VWD). The usefulness of VWF propeptide (VWFpp) in exploring VWF half‐life was assessed in 22 type 1 and 14 type Vicenza VWD patients, and in 30 normal subjects, by comparing the findings on post‐Desmopressin (DDAVP) VWF t1/2 elimination (t1/2el). The VWFpp/VWF antigen ratio (VWFpp ratio) was dramatically increased in type Vicenza VWD (13·02 ± 0·49) when compared to normal subjects (1·45 ± 0·06), whereas it appeared to be normal in all type 1 VWD patients (1·56 ± 0·7), except for the four carrying the C1130F mutation (4·69 ± 0·67). A very short VWF t1/2el was found in type Vicenza VWD (1·3 ± 0·2 h), while all type 1 VWD patients had a t1/2el similar to that of the controls (11·6 ± 1·4 and 15·4 ± 2·5 h respectively), except for the four patients carrying the C1130F mutation, who had a significantly shorter VWF survival (4·1 ± 0·2 h). A significant inverse correlation emerged between VWFpp ratio and VWF t1/2el in both VWD patients and normal subjects. The VWFpp ratio thus seemed very useful for distinguishing between type 1 VWD cases with a normal and a reduced VWF survival, as well as for identifying type Vicenza VWD.
Molecular‐genetic insights in paediatric T‐cell acute lymphoblastic leukaemia
Authors: Van Vlierberghe Pieter , Pieters Rob , Beverloo H. Berna , Meijerink Jules P. P.
Published: August 2008

Paediatric T‐cell acute lymphoblastic leukaemia (T‐ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B‐lineage acute leukaemias. In T‐ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T‐cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco‐ and tumor suppressor genes in T‐ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular‐cytogenetic T‐ALL subgroups, whereas type B abnormalities are found in all major T‐ALL subgroups and synergize with these type A mutations during T‐cell pathogenesis.
Serum C‐reactive protein (CRP) and microalbuminuria in relation to fasting and 2‐h postload plasma glucose in a Chinese population
Authors: Li Xiao‐Ying , Xu Min , Wang Ji‐Guang , Wang Xin‐Jun , Huang Yun , Cheng Qi , Huang Hong‐Er , Li Rui , Xiang Jie , Tan Jiao‐Rong , Dai Meng , Ning Guang
Published: August 2008

Objective  Serum C‐reactive protein (CRP) and microalbuminuria are predictors of cardiovascular disease. The association of these factors of cardiovascular risk with fasting and 2‐h postload plasma glucose in a group of Chinese subjects was investigated.

Design  This was a cross‐sectional cohort study.

Subjects and methods  In 1776 subjects randomly selected from the permanent residents of a community in the city of Shanghai, China, a simplified 75‐g oral glucose tolerance test (fasting and 2‐h postload blood sampling only) was performed, and serum CRP concentrations and urinary albumin : creatinine ratio were measured.

Results  Serum CRP concentration significantly increased from 1·62 mg/l in normoglycaemic subjects to 2·63 mg/l in subjects with impaired glucose regulation, and to 3·09 mg/l in newly diagnosed diabetic patients (P < 0·0001). The corresponding prevalence of microalbuminuria also increased from 4·3% to 6·6% and to 11·4% (P < 0·0001). Both before and after adjustment for confounders, fasting and 2‐h postload plasma glucose levels were significantly associated with serum CRP concentration and the risk of microalbuminuria (P < 0·003). However, the association for CRP tended to be more prominent with 2‐h postload plasma glucose than with fasting plasma glucose. Indeed, with adjustments applied, for 1 SD change in fasting and 2‐h postload plasma glucose concentration, serum CRP concentration increased by 14% and 18% (between the two regression coefficients, P = 0·01), respectively. With similar adjustments, for 1 SD change in fasting and 2‐h postload plasma glucose concentration, the odds of microalbuminuria increased by 28% and 32% (P = 0·28 for the difference between 28% and 32%), respectively.

Conclusions  Our finding suggests that in Chinese plasma glucose, especially 2‐h postload, is associated with biological markers of cardiovascular disease, such as serum CRP concentration and microalbuminuria.
Healthier lifestyle predicts higher circulating testosterone in older men: the Health In Men Study
Authors: Yeap Bu B. , Almeida Osvaldo P. , Hyde Zoë , Norman Paul E. , Chubb S. A. Paul , Jamrozik Konrad , Hankey Graeme J. , Flicker Leon
Published: August 2008

Objective  Circulating testosterone declines during male ageing, and low testosterone may predispose to ill health. We sought to determine whether greater participation in healthy behaviours predicted reduced risk of subsequent lower circulating testosterone in older men.

Design  Cross‐sectional analysis of a population‐based follow‐up study.

Participants  A total of 3453 men aged 65–83 years.

Measurements  Lifestyle score, a tally of eight prudent health‐related behaviours, was determined during 1996–99. Early morning sera collected in 2001–04 were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.

Results  Mean (± SD) time between collection of lifestyle data and blood sampling was 5·7 ± 0·9 years. Lifestyle score correlated with subsequent total testosterone (r = 0·06, P < 0·001) and SHBG (r = 0·07, P < 0·001), but not free testosterone (r = 0·03, P = 0·08) or LH (r = –0·03, P = 0·12). In multivariate analyses, higher lifestyle scores (4 and above) predicted reduced risk of total testosterone and SHBG in the lowest quartile of values. For the highest category (≥ 7), odds ratio (95% CI) for total testosterone and SHBG in the lowest quartile were 0·37 (0·18–0·77) and 0·26 (0·13–0·54), respectively. Lower lifestyle scores including and excluding body mass index predicted higher risk of total testosterone and SHBG in the lowest quartiles.

Conclusions  In men > 65 years old, higher lifestyle score reflecting greater engagement in healthy behaviours predicts higher subsequent total testosterone and SHBG levels. This relationship appears cumulative and may reflect interaction between lifestyle and insulin sensitivity. Successfully promoting healthy behaviours in older men could ameliorate the age‐related decline in circulating testosterone.
Down‐regulation of the PI3‐kinase/Akt pathway by ERK MAP kinase in growth factor signaling
Authors: Hayashi Hideko , Tsuchiya Yoshiki , Nakayama Kei , Satoh Takayuki , Nishida Eisuke
Published: August 2008

The ERK MAP kinase and PI3‐kinase/Akt pathways are major intracellular signaling modules, which are known to regulate diverse cellular processes including cell proliferation, survival and malignant transformation. However, it has not been fully understood how these two pathways interact with each other. Here, we demonstrate that inhibition of the ERK pathway by the MEK inhibitor U0126 or PD98059 significantly potentiates EGF‐ and FGF‐induced Akt phosphorylation at both Thr308 and Ser473. We also show that hyperactivation of the ERK pathway greatly attenuates EGF‐ and FGF‐induced Akt phosphorylation. Furthermore, the enhanced Akt phosphorylation induced by U0126 is inhibited by the PI3‐kinase inhibitor LY294002, and is accompanied by the up‐regulation of Ras activity. These results suggest that the ERK pathway inhibition enhances Akt phosphorylation through the Ras/PI3‐kinase pathway. Thus, our results demonstrate that the ERK pathway negatively modulates the PI3‐kinase/Akt pathway in response to growth factor stimulation.
Secreted CREG inhibits cell proliferation mediated by mannose 6‐phosphate/insulin‐like growth factor II receptor in NIH3T3 fibroblasts
Authors: Han Ya‐Ling , Guo Peng , Sun Ming‐Yu , Guo Liang , Luan Bo , Kang Jian , Yan Cheng‐Hui , Li Shao‐Hua
Published: August 2008

Cellular repressor of E1A‐stimulated genes (CREG) is a recently described glycoprotein that plays a critical role in keeping cells or tissues in mature, homeostatic states. To understand the relationship between CREG and its membrane receptor, mannose 6‐phosphate/insulin‐like growth factor II receptor (M6P/IGF2R), we first generated stable NIH3T3 fibroblasts by transfection of pDS_shCREGs vectors, which produced an approximately 80% decrease in CREG levels both in the lysate and in the media. We used fluorescence activated cell sorting and a bromide deoxyuridine incorporation assay to identify whether CREG knockdown promoted the cell proliferation associated with the increase of IGF‐II in NIH3T3 fibroblasts. Proliferation was markedly inhibited in a concentration‐dependent manner by re‐addition of recombinant CREG protein into the media, and this was mediated by the membrane receptor M6P/IGF2R. We subsequently confirmed the direct interaction of CREG and M6P/IGF2R by both immunoprecipitation‐Western blotting and immunofluorescence staining. We found that expression of CREG correlated with localization of the receptor in NIH3T3 fibroblasts but did not affect its expression. Our findings indicated that CREG might act as a functional regulator of M6P/IGF2R to facilitate binding and trafficking of IGF‐II endocytosis, leading to growth inhibition.
Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophilia
Authors: KLAMROTH R. , GOTTSTEIN S. , ESSERS E. , LANDGRAF H. , WILASCHEK M. , OLDENBURG J.
Published: August 2008

Summary.  In haemophilic joints with high‐grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg−1 bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low‐dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one‐third of the amount consumed before embolization. In conclusion, angiographic embolization with a non‐adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels.
Effect of an antifungal denture liner on the saliva yeast count in patients with denture stomatitis: a pilot study
Authors: GEERTS G. A. V. M. , STUHLINGER M. E. , BASSON N. J.
Published: August 2008

Summary  Although in vitro studies on the release of antifungal agents from tissue conditioners have been done, no in vivo research on the topic could be found. The purpose of this study was to determine the in vivo effect of an antifungal agent released from a tissue conditioner on the salivary yeast count. Forty edentulous patients with denture stomatitis caused by Candida albicans were divided in two groups. Group 1 (control) was treated with a tissue conditioner only. Group 2 was treated with a tissue conditioner incorporating 500 000 U nystatin. Oral rinses were performed by both groups before treatment and every second day during treatment for a period of 14 days. Total yeast counts of the oral rinses were performed and the averages and standard deviations for both groups calculated and logarithm‐transformed data of the counts over time were statistically analysed using the Wilcoxon signed‐rank test. The average oral rinse yeast count of the control group decreased up to day 4. Thereafter, the count increased till the end of the test period. At day 14, the oral rinse yeast level was higher than the pre‐treatment level. The average yeast count of the test group decreased up to day 7. Thereafter, the count increased but remained significantly lower (P = 0·01) than the control group and did not return to its pre‐treatment level. A nystatin‐containing short‐term denture liner significantly decreases the salivary yeast count of patients with denture stomatitis compared with a liner without nystatin.
Effect of different labio‐lingual spaces in tray designs on the displacement of and pressure against a mobile tooth
Authors: NISHI Y. , TSURU K. , KISHITA C. , KAMASHITA Y. , HAMANO T. , NAGAOKA E.
Published: August 2008

Summary  The present study aimed to examine the effect of custom tray designs on the displacement of mobile tooth and local impression pressures during the impression procedure, using partially edentulous simulation models with six anterior teeth containing a mobile tooth prepared in previous studies. The custom trays were designed by altering the thickness of the respective spaces on the labial and lingual sides of the remaining tooth arch. In previous studies, the mobile tooth was displaced in the labial direction and local impression pressures of the mobile tooth were greater against the lingual side than the labial side for all custom tray designs. Furthermore, the custom trays perforated with holes on the lingual side were effective to reduce mobile tooth displacement, labial and lingual impression pressures against the mobile tooth, and the differences between them. Therefore, the present study was performed focusing on the labial and lingual thickness of spaces in custom tray designs. It was found that mobile tooth displacement, labial and lingual impression pressures against the mobile teeth and their differences were less in trays with spaces >3·0 mm thick on both the labial and lingual sides, but markedly greater in trays with a 1·5 mm‐thick space on the labial side. These results indicate that the thickness of spaces on the labial side in the tray should not be reduced to prevent mobile tooth displacement.
Present status of titanium removable dentures – a review of the literature*
Authors: OHKUBO C. , HANATANI S. , HOSOI T.
Published: August 2008

Summary  Although porcelain and zirconium oxide might be used for fixed partial dental prostheses instead of conventional dental metals in the near future, removable partial denture (RPD) frameworks will probably continue to be cast with biocompatible metals. Commercially pure (CP) titanium has appropriate mechanical properties, it is lightweight (low density) compared with conventional dental alloys, and has outstanding biocompatibility that prevents metal allergic reactions. This literature review describes the laboratory conditions needed for fabricating titanium frameworks and the present status of titanium removable prostheses. The use of titanium for the production of cast RPD frameworks has gradually increased. There are no reports about metallic allergy apparently caused by CP titanium dentures. The laboratory drawbacks still remain, such as the lengthy burn‐out, inferior castability and machinability, reaction layer formed on the cast surface, difficulty of polishing, and high initial costs. However, the clinical problems, such as discoloration of the titanium surfaces, unpleasant metal taste, decrease of clasp retention, tendency for plaque to adhere to the surface, detachment of the denture base resin, and severe wear of titanium teeth, have gradually been resolved. Titanium RPD frameworks have never been reported to fail catastrophically. Thus, titanium is recommended as protection against metal allergy, particularly for large‐sized prostheses such as RPDs or complete dentures.
Assessing perceived potential outcomes of prosthodontic treatment in partial and fully edentulous patients
Authors: LELES C. R. , MORANDINI W. J. , Da SILVA É. T. , De F. NUNES M. , FREIRE M. C. M.
Published: August 2008

Summary  The aim was to develop an instrument to measure and to explore the perception of potential outcomes of prosthodontic treatment in partial and fully edentulous patients, including benefits, risks and consequences of non replacement of missing teeth. It was also aimed to assess the influence of clinical and socio‐demographic variables on the perception of potential outcomes. Using a two‐phase data collection (open‐ended and closed‐form), a scale was developed containing 41 statements to measure subject’s perception scores in a 5‐point Likert‐type scale (1, strongly disagree; 2, disagree; 3, neutral; 4, agree; 5, strongly agree). In the second phase 126 partially or fully edentulous subjects were interviewed. Influence of age, gender and clinical variables on perceived outcomes were tested using one‐way anova, independent t‐test and two‐way anova (general linear model). Respondents’ mean age was 51·8 years (s.d.=12·3), and 74% were female. Cronbach’s alpha coefficient of the scale and subscales ranged from 0·70 to 0·90. Patients’ mean scores ranged from 2·37 to 4·88 (mean=4·25; s.d.=0·65), indicating that subjects tended to agree with the proposed affirmatives (scores 4 and 5). Perception scores were influenced by age, gender, edentulous spaces and use of prosthodontics. Older subjects, female, those with higher number of missing teeth and who have been previously treated had greater perception of benefits and risks of prosthodontic treatment. It was concluded that the proposed instrument was suitable for measuring subjects’ perception of potential outcomes of prosthodontic treatment.
Placental transfer and pharmacokinetics of allopurinol in late pregnant sows and their fetuses
Authors: VAN DIJK A. J. , PARVIZI N. , TAVERNE M. A. M. , FINK‐GREMMELS J.
Published: August 2008

Xanthine oxidoreductase (XOR) is a key enzyme in the evolvement of reperfusion injury resulting from birth asphyxia, a common cause of decreased viability and perinatal mortality in newborn piglets under farm conditions. At present no standard pharmacological intervention strategy is available to reduce these adverse effects of birth asphyxia. In the present study we aimed to evaluate placental transfer of allopurinol, an inhibitor of XOR. For this purpose, fetal catheterization of the jugular vein was conducted in five late pregnant sows (one fetus per sow). At 24–48 h after surgery, sows received allopurinol (15 mg/kg body weight; i.v.) and pharmacokinetics of allopurinol and its active metabolite oxypurinol were measured in both late pregnant sows and fetuses. Maternal and fetal blood samples were collected during and after allopurinol administration. MaternalCmaxvalues averaged 41.90 μg/mL (allopurinol) and 3.68 μg/mL (oxypurinol). Allopurinol crossed the placental barrier as shown by the average fetalCmaxvalues of 5.05 μg/mL at 1.47 h after allopurinol administration to the sow. In only one fetus low plasma oxypurinol concentrations were found. Incubations of subcellular hepatic fractions of sows and 24‐h‐old piglets confirmed that allopurinol could be metabolized into oxypurinol. In conclusion, we demonstrated that allopurinol can cross the placental barrier, a prerequisite for further studies evaluating the use of allopurinol as a neuroprotective agent to reduce the adverse effects following birth asphyxia in neonatal piglets.
Signal transduction meets systems biology: deciphering specificity determinants for protein–protein interactions
Authors: Bourret Robert B.
Published: August 2008

Two recent papers (Gao et al. 2008 and Skerker et al. 2008) describe investigations into the specificity of protein–protein interactions that occur during signal transduction by two‐component regulatory systems. This MicroCommentary summarizes and provides context for the reported findings. The results offer insights into molecular determinants that provide specificity to maintain signal separation and thus prevent deleterious cross‐talk between pathways, as well as the potential extent and nature of interactions that may combine signals to achieve beneficial cross‐regulation among pathways. The methods employed are suitable for application to other systems.
Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients
Authors: Schoepfer A. M. , Schaffer T. , Seibold‐schmid B. , Müller S. , Seibold F.
Published: August 2008

Abstract  One of the several possible causes of irritable bowel syndrome (IBS) is thought to be low‐grade mucosal inflammation. Flagellin, the primary structural component of bacterial flagellae, was shown in inflammatory bowel disease patients to activate the innate and adaptive immunity. It has not yet been conclusively established if IBS patients show reactivity to luminal antigens. In 266 patients [112 IBS, 61 Crohn’s disease (CD), 50 ulcerative colitis (UC) and 43 healthy controls (HC)], we measured antibodies to flagellin (FAB, types A4‐Fla2 and Fla‐X), anti‐Saccharomyces cerevisiae antibodies (ASCA) (both ELISA), antipancreas antibodies (PAB) and perinuclear antineutrophil cytoplasmatic antibodies (p‐ANCA) (both IF). All IBS patients had normal fecal calprotectin (mean 21 μg mL−1, SD 6.6) and fulfilled the ROME II criteria. Frequencies of antibodies in patients with IBS, CD, UC and HC, respectively, are as follows (in per cent): antibodies against A4‐Fla2: 29/48/8/7; antibodies against Fla‐X: 26/52/10/7; ASCA: 6/59/0/2; p‐ANCA: 0/10/52/0; and PAB: 0/28/0/0. Antibodies against A4‐Fla2 and Fla‐X were significantly more frequent in IBS patients than in HC (P = 0.004 and P = 0.009). Antibodies to A4‐Fla2 and Fla‐X were significantly more frequent in IBS patients with antecedent gastroenteritis compared to non‐postinfectious IBS patients (P = 0.002 and P = 0.012). In contrast to ASCA, PAB and p‐ANCA, antibodies against A4‐Fla2 and Fla‐X were found significantly more often in IBS patients, particularly in those with postinfectious IBS, compared to HC. This observation supports the concept that immune reactivity to luminal antigens has a putative role in the development of IBS, at least in a subset of patients.
Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecation
Authors: Shafton A. D. , Sanger G. J. , Witherington J. , Brown J. D. , Muir A. , Butler S. , Abberley L. , Shimizu Y. , Furness J. B.
Published: August 2008

Abstract  Agonists of ghrelin receptors that cross the blood–brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo‐sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood–brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1–10 nmol L−1, but was >1000‐fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood ratio at steady state was 0.7 : 1. GSK894281 administered orally (1–100 mg kg−1) caused a prompt, dose‐related production of faecal pellets; at 10 mg kg−1 faecal output was four times greater than after carrier. The output was the greatest in the first half hour and subsided over the next 90 min. At an oral dose of 10 mg kg−1, the compound was effective on eight successive days. Faecal output was, on average, increased threefold over control in the 2 h after administration on each of the 8 days. This dose also significantly increased food consumption. Rats showed no adverse behavioural effects to the drug on a single application, but at the end of a week of administration they avoided the gavaging pipette. Oral administration of ghrelin receptor agonists that enter the central nervous system could possibly be used to relieve acute cases of constipation or to clear the bowel for colonoscopy.
Electrochemical monitoring of nitric oxide released by myenteric neurons of the guinea pig ileum
Authors: Patel B. A. , Galligan J. J. , Swain G. M. , Bian X.
Published: August 2008

Abstract Nitric oxide (NO) released by myenteric neurons in isolated segments of guinea pig ileum was monitoredin vitrousing continuous amperometry. NO was detected as an oxidation current recorded with a boron‐doped diamond microelectrode held at 1 Vvsa Ag|AgCl reference electrode. This potential was sufficient to oxidize NO. Longitudinal muscle‐myenteric plexus (LMMP) and circular muscle strip preparations were used. In the LMMP preparation, NO release was evoked by superfusion of 1 μmol L−1nicotine, which activates nicotinic acetylcholine receptors expressed by myenteric neurons and myenteric nerve endings. The oxidation current was ascribed to NO based on the following observations: (i) no response was detected at less positive potentials (0.75 V) at which only catecholamines and biogenic amines are oxidized, (ii) the current was abolished in the presence of the nitric oxide synthase antagonist,N‐nitro‐l‐arginine (l‐NNA) and (iii) oxidation currents were attenuated by addition of the NO scavenger, myoglobin, to the superfusing solution. In the LMMP preparation, stimulated release produced a maximum current that corresponded nominally to 46 nmol L−1of NO. The oxidation currents decreased to 10 and 2 nmol L−1, respectively, when the tissue was perfused with tetrodotoxin andl‐NNA. Oxidation currents recorded from circular muscle strips (stimulated using nicotine) were threefold larger than those recorded from the LMMP. This study shows that NO release can be detected from variousin vitropreparations of the guinea pig ileum using real‐time electroanalytical techniques.
Influence of abuse history on gastric sensorimotor function in functional dyspepsia
Authors: Geeraerts B. , Van Oudenhove L. , Fischler B. , Vandenberghe J. , Caenepeel P. , Janssens J. , Tack J.
Published: August 2008

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self‐report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty‐four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P = 0.007]. The corresponding intra‐balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P = 0.013 and 579 ± 19 vs 423 ± 79 mL, P = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.
Sediment waves in a modern high‐energy glacilacustrine environment
Authors: GILBERT ROBERT , CROOKSHANKS SARAH
Published: August 2008

A 4·7 km2 field of sediment waves occurs in front of the Slims River delta in Kluane Lake, the largest lake in the Yukon Territory. Slims River heads in the Kaskawulsh Glacier, part of the St Elias Ice Field and discharges up to 400 m3 s−1 of water with suspended sediment concentrations of up to 7 g l−1. The 19 km long sandur of Slims River was created in the past 400 years since Kaskawulsh Glacier advanced and dammed the lake and the sandur has advanced into Kluane Lake at an average rate of 48 m a−1. However, this rate is decreasing as flow is diverted from Slims River because of the retreat of the Kaskawulsh Glacier. The sandur and a road constructed on the delta remove coarse‐grained sediment, so the river delivers dominantly mud to the lake. Inflow during summer generates quasi‐continuous turbidity currents with velocities up to 0·6 m s−1. The front of the delta consists of a plane surface sloping lakeward at 0·0188 (1·08°). A field of sediment waves averaging 130 m in length and 2·3 m in amplitude has developed on this surface. Slopes on the waves vary from −0·067 (−3·83°, i.e. sloping in the opposite direction to the regional slope) to 0·135 (7·69°). The internal structure of the sediment waves, as documented by seismic profiling, shows that sedimentation on the stoss portion of the wave averages 2·7 times that on the lee portion. Rates of sediment accumulation in the wave field are about 0·3 m a−1, so these lacustrine waves have formed in a much shorter period of time (less than 200 years) and are advancing upslope towards the delta much more quickly (1 to 2 m a−1) than typical marine sediment waves. These waves formed on the flat surface of the lake floor, apparently in the absence of pre‐existing forms, and they are altered and destroyed as the wave field advances and the characteristics of the turbidity currents change.
Vertical gradational variability of fines deposited in a gravel framework
Authors: GIBSON STANFORD , ABRAHAM DAVID , HEATH RONALD , SCHOELLHAMER DAVID
Published: August 2008

Vertical gradational structures develop as sand infiltrates into static gravel beds. Understanding the vertical distribution of interstitial sand deposits will improve predictions of ecological suitability and hyporheic hydrodynamics. A series of flume experiments was performed to investigate fine infiltration processes. Four sand distributions were introduced into flows over gravel beds. After each experiment, bed cores were extracted and analysed in vertical layers to examine the gradational trends with depth. Vertical trends of fine content were highly sensitive to the relative grain‐size distributions of the gravel bed and the introduced sand. For experiments with d15gravel/d85sand ratios 15·4 and larger unimpeded static percolation was observed, where sand filled the voids relatively uniformly from the bottom of the gravel layer to the top. Experiments with ratios 10·6 and smaller bridged. Sand clogged a thin layer of gravel pores near the bed surface, precluding subsequent infiltration. Interstitial sand deposits fined with depth of penetration for all experiments which was the result of three distinct but overlapping processes. (i) Granular sorting: As particles fell through the substrate, smaller material preferentially passed through the voids deeper into the gravel. (ii) Bed‐load sorting: Size segregation occurs in the wake of the leading bed form as smaller particles saltate further and settle first. (iii) Hydraulic sorting: Smaller sand was transported preferentially as suspended load filling the deep voids of the furthest flume positions downstream. Finally, when the experiments that formed a bridge layer were replicated with higher bed shear stresses, less interstitial sand deposition was observed. Higher shear stresses transported coarse particles downstream more efficiently causing bridge layers to form earlier and allowing less time for suspended load to settle into the deeper substrate pores before the pathways were closed.
Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids
Authors: Nasir Lubna , Campo M Saveria
Published: August 2008

Bovine papillomavirus (BPV) is perhaps the most extensively studied animal papillomavirus. In cattle BPVs induce benign tumours of cutaneous or mucosal epithelia, called papillomas or warts. Cattle papillomas are benign tumours and generally regress without eliciting any serious clinical problems in the host, but occasionally persist and provide the focus for malignant transformation to squamous cell carcinoma, as in the case of cancer of the urinary bladder and cancer of the upper alimentary canal. BPV is the only papillomavirus that jumps species: the virus also infects equids, and gives rise to fibroblastic tumours called sarcoids. Sarcoids very rarely regress, more often they persist and can be locally aggressive. These tumours are the most common dermatological tumour of equids worldwide.

The purpose of this review is to discuss the biology of BPV, the biology of bovine tumours and equine sarcoids, and present the current understanding of BPV in tumour pathogenesis in its natural host, cattle, and in its heterologous host, equids. Finally, the use of anti‐BPV vaccines as a therapy for equine sarcoids will be discussed. Only limited information on the clinical or pathological aspects of either bovine or equine tumours will be provided as this subject has been extensively addressed previously.
The efficacy of commercially available veterinary diets recommended for dogs with atopic dermatitis
Authors: Glos Katharina , Linek Monika , Loewenstein Christine , Mayer Ursula , Mueller Ralf S.
Published: August 2008

The classical treatments for dogs with atopic dermatitis have traditionally been oral antipruritic drugs, allergen‐specific immunotherapy and topical therapy. Fifty dogs with atopic dermatitis were included in this multicentred, double‐blinded, randomized study to compare clinical response to an 8‐week period of feeding one of three commercial veterinary foods marketed for dogs with atopic dermatitis (diets A–C) or a widely distributed supermarket food (diet D). Atopic dermatitis was diagnosed using Willemse's criteria and through the exclusion of differential diagnoses. Fourteen dogs were assigned to diet A and 12 dogs each to diet B, C or D. Flea and tick control using a monthly fipronil spot‐on product was administered for a minimum of 4 weeks prior to inclusion in the study and during the study period. Evaluations were made monthly. These included lesion scores, using an established scoring system (canine atopic dermatitis extent and severity index, CADESI‐03) and owner evaluation of pruritus level using a visual analogue scale. After 8 weeks on the new diets, there was a significant improvement in CADESI and pruritus scores with diet B (Wilcoxon test,P = 0.043 and pairedt‐test,P = 0.012, respectively), in pruritus scores with diet A (pairedt‐test,P = 0.019) and in CADESI scores with diet D (Wilcoxon test,P = 0.037). No significant changes were detected with diet C. Based on the results of this study, in addition to the conventional therapies, changing the diet of dogs with atopic dermatitis may be a useful adjunctive therapeutic measure.
Cutaneous pythiosis in a nontravelled California horse
Authors: White Stephen D. , Ghoddusi Majid , Grooters Amy M. , Jones Kathryn
Published: August 2008

An 18‐year‐old Arabian mare was examined with a large mass on the left hind pastern and fetlock. The mare was located in the Central Valley of northern California, and had never been out of the state. Routine histopathological processing and examination of biopsy samples from the mass showed several hyphal organisms that were delineated with a silver stain. Using immunohistochemistry the organism was diagnosed as Pythium insidiosum. The owner declined debulking surgery, and despite treatment with an immunotherapeutic vaccine, the horse's condition deteriorated leading to euthanasia.
Microbiological and histopathological features of canine acral lick dermatitis
Authors: Shumaker A.K. , Angus J.C. , Coyner K.S. , Loeffler D.G. , Rankin S.C. , Lewis T.P.
Published: August 2008

The purpose of this study was to investigate microbiological and histopathological features of canine acral lick dermatitis (ALD). Microbial characteristics of ALD are poorly described in current literature. If infection is recognized, antimicrobial selection is usually empirical, based on appearance, cytology or surface culture, rather than deep tissue culture. It was hypothesized that cultures obtained from deep tissue would yield different results than predicted by surface culture and cytology, and that isolates from ALD have unpredictable susceptibility patterns showing resistance to antibiotics routinely administered for canine pyoderma. Biopsies were obtained from 31 lesions and submitted for aerobic, anaerobic and fungal culture, and histopathological evaluation. Surface aerobic culture and susceptibility and cytology were obtained for comparison in 22 dogs. Skin scrapings and dermatophyte culture were performed. Bacteria were isolated in 30 of 31 cases.Staphylococcus intermediuswas isolated in 58% of deep cultures. Twenty per cent of deep isolates were methicillin‐resistantStaphylococcusspecies. Forty‐eight per cent of cases yielded organisms defined as multidrug resistant on deep culture. Only 57% and 55% of bacteria isolated from tissue culture were sensitive to amoxicillin‐clavulanic acid and cefazolin, respectively. Cytology and superficial cultures did not correlate well with deep cultures. Surface culture predicted deep tissue isolates in eight of 22 cases. Microsporum gypseum was isolated from one dog. Histopathological features included acanthosis, follicular elongation, lymphoplasmacytic dermal inflammation, folliculitis, furunculosis, perihidradenitis, hidradenitis and vertical streaking fibrosis. Lesions associated with ALD warrant tissue bacterial cultures as the majority of cases yielded positive growth of bacteria differing from superficial culture and often resistant to empirical drugs.
PRECLINICAL STUDY: Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats
Authors: Schneider Miriam , Schömig Edgar , Leweke F. Markus
Published: August 2008

Although cannabis belongs to the most widely used drugs among adolescents, little is known about its acute and lasting neurobehavioral effects during critical developmental periods. In the present study we investigated acute and long‐term behavioral effects of the cannabinoid agonist WIN 55,212‐2 (WIN) in pubertal and adult rats. Chronic WIN (1.2 mg/kg)/vehicle treatment was extended over 25 days throughout puberty, from postnatal day (pd) 40 to pd 65, or for a similar time period in adult rats (> pd 80). All animals were tested at three time points for object/social recognition memory, social interaction and spontaneous social behavior. First, acute cannabinoid effects were investigated directly after the first injection. Additionally, behavioral performance was retested 24 hours and 15 days after cessation of WIN treatment. Chronic pubertal WIN treatment induced persistent object/social recognition deficits, indicating a general impairment in short‐term information processing. Lasting disturbances in social behavior, social play and self‐grooming were also found. Furthermore, behavioral deficits seen after acute WIN administration were more pronounced in pubertal than in adult rats. These results confirm our recent findings that chronic pubertal cannabinoid treatment leads to lasting behavioral alterations in adulthood, and they show that acute cannabinoid administration induces more severe behavioral deficits in pubertal rats than in mature animals. We therefore conclude that an immature brain is more susceptible to the acute and chronic effects of exogenous cannabinoids than an adult organism, which might be explained by an overactive endocannabinoid system and concomittant maturational disturbances in further neurotransmitter systems during pubertal development.
REVIEW: The systems view in addiction research
Authors: Gebicke‐Haerter Peter J. , Tretter Felix
Published: August 2008

The wealth of information accessible on the molecular level after completion of sequencing of the human and other genomes and in conjunction with new high‐throughput technologies like microarrays has paved the way for research on whole systems rather than on single components. Here we describe exemplarily the construction of a rather complex molecular network involved in alcohol addiction by using information from DNA‐microarray studies in alcohol‐dependent animals. In this network, haemoglobin downregulation in different parts of the brain reward system plays a central role in affecting synaptic plasticity, circadian rhythmicity and opioid receptors. Furthermore, we discuss the dynamic aspect of biological systems with respect to repeated and intermittent drug intake. This aspect can best be captured by the allostatic model on the molecular level. Using a molecular oscillator model where levels of oscillations are changed by repetitive drug administration, changes in set point adjustment are described that underlay allostatic shifts in drug reinforcement processes.
Post‐transplant diabetes mellitus in children following renal transplantation
Authors: Prokai A. , Fekete A. , Kis E. , Reusz G. S. , Sallay P. , Korner A. , Wagner L. , Tulassay T. , Szabo A. J.
Published: August 2008

Abstract:  PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA‐based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post‐transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.