bluuebunny/crossref_metadata_2025 huggingface dataset:
γδ T lymphocytes kill T regulatory cells through CD1d
Authors: Huber Sally A.
Published: August 2010

Coxsackievirus B3 (CVB3) induces myocarditis, an inflammation of the myocardium, in C57Bl/6 male mice but not in mice lacking γδ+ T cells [γδ knockout (γδKO)]. Suppression of myocarditis in γδKO mice corresponds to an increase in CD4+ CD25+ FoxP3+ T regulatory cells. A subpopulation of the T regulatory cells in infected γδKO mice expressed high levels of CD1d, a non‐classical major histocompatibility complex class 1‐like molecule. Adoptive transfer of CD1d+ and CD1d− CD4+ CD25+ cells into infected C57Bl/6 recipients showed that the CD1d+ subpopulation is substantially more suppressive than the CD1d− subpopulation. T cells expressing the γδ T‐cell receptor comprised approximately 30–50% of the infiltrating lymphoid cells in the hearts of myocarditic C57Bl/6 mice and approximately half of the γδ+ cells expressed the Vγ4 T‐cell receptor. The Vγ4+ cells lysed T regulatory cells from γδKO mice but not from wild‐type (C57Bl/6) animals. Lysis was inhibited by antibody to CD1d and zVAD‐fmk, a pan‐caspase inhibitor. The Vγ4−γδ+ cells were not lytic to T regulatory cells and did not promote myocarditis. These results demonstrate that Vγ4+ cells selectively abrogate T regulatory cells through recognition of CD1d expressed on the regulatory cells and caspase‐dependent apoptosis.
Incidence of dentinal defects after root canal filling procedures
Authors: Shemesh H. , Wesselink P. R. , Wu M.‐K.
Published: August 2010

Shemesh H, Wesselink PR, Wu M‐K. Incidence of dentinal defects after root canal filling procedures. International Endodontic Journal, 43, 995–1000, 2010.

Aim  To compare the incidence of dentinal defects (cracks and craze lines) after root canal preparation, lateral compaction and continuous wave compaction of gutta‐percha and AH26 sealer.

Methodology  Two hundred mandibular premolar teeth were divided into four groups with similar average canal diameters (n = 50). One group was left untreated and served as the control. The other three groups were prepared with ProTaper rotary instruments up to size F4. After preparation, one group was left unfilled while two groups were filled with gutta‐percha and AH26 using either lateral compaction or the continuous wave technique. Roots were then sectioned at 3, 6 and 9 mm from the apex and inspected under a microscope. The appearance of dentinal defects was noted as well as the minimum and mean remaining dentine thickness. Chi‐square tests were performed to compare the incidence of dentinal defects between the groups (α = 0.05), and Pearson correlation test was performed to check the correlation between defects and root level or remaining dentine thickness.

Results  The unprepared control group had no dentinal defects. The other groups exhibited significantly more defects than the unprepared group (P < 0.05). There was no difference in the incidence of defects between the two filling techniques. There was no correlation between the appearance of defects and level of the root or remaining dentine thickness.

Conclusions  In extracted teeth, dentinal defects were observed in roots filled with gutta‐percha and AH26 using the lateral compaction and continuous wave techniques.
Root canal debridement using manual dynamic agitation or the EndoVac for final irrigation in a closed system and an open system
Authors: Parente J. M. , Loushine R. J. , Susin L. , Gu L. , Looney S. W. , Weller R. N. , Pashley D. H. , Tay F. R.
Published: August 2010

Parente JM, Loushine RJ, Susin L, Gu L, Looney SW, Weller RN, Pashley DH, Tay FR. Root canal debridement using manual dynamic agitation or the EndoVac for final irrigation in a closed system and an open system. International Endodontic Journal, 43, 1001–1012, 2010.

Aim  This study examined canal debridement efficacy by testing the null hypothesis that there is no difference between a ‘Closed’ and an ‘Open’ system design in smear layer and debris removal using either manual dynamic agitation or the EndoVac for irrigant delivery.

Methodology  Forty teeth were divided into four groups and submitted to a standardized instrumentation protocol. Final irrigation was performed with either manual dynamic agitation or the EndoVac on groups of teeth with or without a sealed apical foramen. Smear and debris scores were evaluated using SEM and analysed using Cochran–Mantel–Haenszel statistic.

Results  The ability of manual dynamic agitation to remove smear layer and debris in a closed canal system was significantly less effective than in an open canal system and significantly less effective than the EndoVac (P < 0.001).

Conclusion  The null hypothesis was rejected; the presence of a sealed apical foramen adversely affected debridement efficacy when using manual dynamic agitation but not the EndoVac. Apical negative pressure irrigation is an effective method to overcome the fluid dynamics challenges inherent in closed canal systems.
Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours
Authors: Bartkova J. , Moudry P. , Hodny Z. , Lukas J. , Rajpert‐De Meyts E. , Bartek J.
Published: August 2010

Heterochromatinization has been implicated in fundamental biological and pathological processes including differentiation, senescence, ageing and tumourigenesis; however, little is known about its regulation and roles in human cells and tissues in vivo. Here, we show distinct cell‐type‐ and cancer‐stage‐associated patterns of key heterochromatin marks: histone H3 trimethylated at lysine 9 (H3K9me3) and heterochromatic adaptor proteins HP1α and HP1γ, compared with the γH2AX marker of endogenously activated DNA damage response (DDR) and proliferation markers in normal human foetal (n = 4) and adult (n = 29) testes, pre‐invasive carcinoma in situ (CIS; n = 26) lesions and a series of overt germ cell tumours, including seminomas (n = 26), embryonal carcinomas (n = 18) and teratomas (n = 11). Among striking findings were high levels of HP1γ in foetal gonocytes, CIS and seminomas; enhanced multimarker heterochromatinization without DDR activation in CIS; and enhanced HP1α in teratoma structures with epithelial and neuronal differentiation. Differential expression of the three heterochromatin markers suggests their partly non‐overlapping roles, and separation of heterochromatinization from DDR activation highlights distinct responses of germ cells vs. somatic tissues in early tumourigenesis. Conceptually interesting findings were that subsets of human cells in vivo proliferate despite enhanced heterochromatinization, and that cells can strongly express even multiple heterochromatin features in the absence of functional retinoblastoma protein and without DDR activation. Overall, these results provide novel insights into cell‐related and tumour‐related diversity of heterochromatin in human tissues in vivo, relevant for andrology and intrinsic anti‐tumour defence roles attributed to activated DDR and cellular senescence.
Nurses’ use of non‐pharmacological methods in children’s postoperative pain management: educational intervention study
Authors: He Hong‐Gu , Jahja Riawati , Lee Tat‐Leang , Ang Emily Neo Kim , Sinnappan Rajammal , Vehviläinen‐Julkunen Katri , Chan Moon Fai
Published: August 2010

he h.‐g., jahja r., lee t.‐l., ang e.n.k., sinnappan r., vehviläinen‐julkunen k. & chan m.f. (2010) Nurses’ use of non‐pharmacological methods in children’s postoperative pain management: educational intervention study. Journal of Advanced Nursing 66(11), 2398–2409.

Aim.  This paper is a report of study of the impact of an educational intervention in pain management on nurses’ self‐reported use of non‐pharmacological methods for children’s postoperative pain relief and their perceptions of barriers that limited their use of these methods.

Background.  Non‐pharmacological methods have been shown to be effective in relieving pain; however, many barriers, including lack of knowledge, limit nurses’ use of these methods. Pain education is a promising strategy for changing nursing practice, but only a few authors have examined the effectiveness of educational interventions for nurses to help relieve children’s postoperative pain.

Methods.  A quasi‐experimental one‐group pre‐ and post‐test design was used. Questionnaire surveys were conducted with a convenience sample of 108 Registered Nurses in two public hospitals in Singapore in 2008.

Results.  Statistically significant increases were found in nurses’ self‐reported use of imagery, positive reinforcement, thermal regulation, massage and positioning in the postintervention survey. Before the intervention, these methods were less frequently used compared to other methods. Heavy workload/lack of time and the child’s inability to cooperate were the most commonly reported barriers at pre‐ and post‐test.

Conclusion.  The educational intervention had a positive effect on nurses’ use of several non‐pharmacological methods. Regular dissemination of updated information to nurses on these pain management methods is recommended to maintain the positive changes. Nevertheless, education alone was not sufficient to optimize nurses’ use of these methods, as various barriers limited their practice.
What informs parents’ decision‐making about childhood vaccinations?
Authors: Austvoll‐Dahlgren Astrid , Helseth Sølvi
Published: August 2010

austvoll‐dahlgren a. & helseth s. (2010) What informs parents’ decision‐making about childhood vaccinations? Journal of Advanced Nursing 66(11), 2421–2430.

Aim.  This paper is a report of a study conducted to identify parents’ decision‐making processes in relation to childhood vaccinations, including barriers and facilitators to searching for information.

Background.  Decision‐making about childhood vaccinations is complex. Access to the best available evidence and the ability to obtain and understand such information are necessary for effective participation in decision‐making.

Methods.  A grounded theory approach was used, with semi‐structured interviews and focus groups with parents (n = 10) and public health nurses (n = 16) conducted in 2008. Data were derived through incident‐to‐incident and axial coding.

Findings.  Being positive towards vaccination and being decided were found to be main barriers to participation and obtaining information; other factors were perceptions about own abilities and capacity. Public health nurses were the parents’ most important source of information, but tended to inform to facilitate vaccinations. Issues related to this and being inadequately informed were that some parents expressed low confidence about the decision they had made and uncertainty about their rights and responsibilities in decision‐making.

Conclusion.  Information delivered by public health nurses should not facilitate a specific choice but rather be balanced, explaining the benefits and harms, and accompanied by a qualified recommendation. Useful tools to improve practice may include checklists for shared decision‐making and guidelines about trustworthy websites.
Population‐specific Mini Nutritional Assessment can improve mortality‐risk‐predicting ability in institutionalised older Taiwanese
Authors: Tsai Alan C , Ku Pei‐Yu , Tsai Jeng‐Dau
Published: August 2010

Aim and objectives.  The study determined whether a new version of the Mini Nutritional Assessment that adopted population‐specific anthropometric cut‐points would improve the mortality‐predicting ability in institutionalised Taiwanese older people.

Background.  Routine screening is the key for detecting emerging malnutrition, but the tool must be simple, reliable and easy‐to‐use to be well accepted. The Mini Nutritional Assessment can meet these requirements, but for non‐Western populations, modifications based on anthropometric considerations are needed.

Design.  The study purposively sampled 208 residents, aged >65 years, of a long‐term care institution in Central Taiwan. Subjects were free of acute infection/disease and able to communicate. A university human‐subject‐study ethics committee approved the protocol.

Methods.  The study included biochemical measurements and a structured questionnaire for eliciting personal data and answers to questions in the Mini Nutritional Assessment. Follow‐up survival/mortality was tracked for two consecutive six‐month periods and analysed according to nutritional statuses graded with the original or a modified Mini Nutritional Assessment. The modified version adopted population‐specific anthropometric cut‐points and was without body mass index.

Results.  The modification improved the mortality‐predictive ability. Mortality rates for the first six months were 8·7, 3·9 and 0% according to the original Mini Nutritional Assessment and 10·6, 3·4 and 0% according to the modified version for subjects rated malnourished, at risk of malnutrition and normal, respectively. The mortality‐predictive ability of both versions weakened after six months.

Conclusion.  Both versions can predict follow‐up mortality, but the modified version has improved ability. For best results, the tool should be applied every six months or less (shorter for more frail older people) to screen for new cases of at‐risk individuals.

Relevance to clinical practice.  The Mini Nutritional Assessment that adopts population‐specific anthropometric cut‐points may have improved nutritional‐risk and mortality‐risk predictive abilities. The tool can help care‐workers detect emerging nutritional problems and enable timely intervention. Routine use of the tool may help improve the quality of care.
Attitudes towards gestational diabetes among a multiethnic cohort in Australia
Authors: Carolan Mary , Steele Cheryl , Margetts Heather
Published: August 2010

Aims.  This study aimed to examine the attitudes and beliefs towards gestational diabetes of a multiethnic sample of pregnant women with gestational diabetes.

Background.  Women from non‐Caucasian background are disproportionately represented in gestational diabetes statistics. This is of particular importance in multicultural Australia, where increasing numbers of non‐Caucasian women give birth.

Design.  Cross‐sectional survey.

Methods.  The Diabetes Attitude Scale, version 3 was administered to 200 women with gestational diabetes from Vietnamese, Indian, Filipino and Caucasian backgrounds.

Results.  A total of 143 questionnaires were returned indicating a response rate of 71·5%. There were significant between group differences in terms of educational level (p = 0·001) and English fluency (p = 0·001). Lower educational level, though not English language fluency, was associated with poorer appreciation of gestational diabetes as a serious condition and also with a lower valuing of tight glucose control. This effect was seen irrespective of ethnic group. Indian and Vietnamese women indicated a lower valuing of patient autonomy and also reported less negative psychological effects than Caucasian and Filipino women.

Conclusions.  Women from non‐Caucasian ethnicities may be at risk of poorer self‐management of gestational diabetes related to lower education, lower health literacy and a lower appreciation of gestational diabetes as a serious condition.

Relevance to clinical practice.  Nurses and midwives provide information and advice to women with gestational diabetes. Knowledge about factors that impact on attitude towards gestational diabetes among multiethnic populations is important for developing educational programmes to address their needs.
Doctor characteristics and prescribing antibiotics for urinary tract infections: the experience of an Asian country
Authors: Lin Yi‐Chun , Lin Hsiu‐Chen , Lin Herng‐Ching
Published: August 2010

Rationale, aims and objectives  This study aims to explore the relationship between doctor characteristics and prescribing behaviour for patients with urinary tract infections (UTIs) using a 2‐year population‐based data set in Taiwan.

Methods  This study used data from the Taiwan National Health Insurance Research Database. Our study sample consists of first‐time ambulatory care visits for treatment of UTIs among female patients between 2005 and 2006 (n = 45 934). The primary outcome studied was ‘whether a broad‐spectrum antibiotic was prescribed’, and the key independent variables were ‘doctor characteristics’. Doctor characteristics included gender, age (<41, 41–50, >50), specialty, type (hospital‐based vs. office‐based) and practice location. Multivariate logistic regression analysis using generalized estimated equations was performed to assess the adjusted odds ratio of the doctors using broad‐spectrum antibiotics.

Results  Among the sampled patients, 13.5% were prescribed broad‐spectrum antibiotics at their first visit for treatment of UTIs. The adjusted odds of prescribing second‐line antibiotics for doctors aged between 41–50 years and >50 years were 0.80 (P < 0.001) and 0.90 (P = 0.007) times, respectively, that of doctors aged <41 years. Doctors specializing in family medicine were 1.10 (P = 0.006) times more likely than doctors specializing in obstetrics and gynaecology to prescribe broad‐spectrum, and office‐based doctors were 1.41 (P < 0.001) times more likely than hospital‐based doctors to do so.

Conclusions  We conclude that there is variation in doctor prescribing behaviour of antimicrobial therapy for UTIs, after adjusting for possible confounding factors. Continuing medical education and intervention should be designed for doctor groups with undesirable performance in prescribing antibiotics.
Are interventions recommended by pharmacists during Home Medicines Review evidence‐based?
Authors: Castelino Ronald L. , Bajorek Beata V. , Chen Timothy F.
Published: August 2010

Introduction  Over the past decade medication review services have been implemented in many countries, including Australia, UK and USA. Although, the attitudes and barriers to the implementation of evidence‐based medicine have been investigated, the extent to which medication review recommendations are evidence‐based is not known.

Objective  To determine (1) the extent to which pharmacist's recommendations during medication review services were consistent with the evidence‐based guides at the time of the review; and (2) the nature and extent of drug‐related problems (DRPs) and the actions recommended by pharmacists to resolve DRPs.

Method  A retrospective review of Home Medicines Review cases performed on 224 community‐dwelling older people (65 years or older). The chi‐squared test for categorical variables was used to compare the proportion of recommendations that were evidence‐based and recommendations for which no evidence could be identified in the most common Australian information sources. DRPs and the actions recommended to resolve the DRPs were classified according to previously employed criteria.

Results  Pharmacists made a total of 1114 therapeutic recommendations to general practitioners, of which 964 required supporting pharmacotherapeutic evidence. The majority (94%) of the pharmacists' recommendations were in accordance with the evidence‐based guides, as compared with the recommendations for which no evidence could be identified (P < 0.001). Pharmacists reported that 98% of the patients had at least one problem with use of their medication detected.

Conclusion  The majority of the actions recommended by pharmacists during the medication review process were consistent with the literature embedded in key Australian information sources. Medication management in older people is complex and challenging, as highlighted by the DRPs identified in 98% of our patients. A suitably trained pharmacist, with full access to the patient, medical record and supporting resources, can help to improve the quality use of medicines in this at‐risk population.
Use of a clinical decision support system to increase osteoporosis screening
Authors: DeJesus Ramona S. , Angstman Kurt B. , Kesman Rebecca , Stroebel Robert J. , Bernard Matthew E. , Scheitel Sidna M. , Hunt Vicki L. , Rahman Ahmed S. , Chaudhry Rajeev
Published: August 2010

Background  In 2002, the US Preventive Services Task Force recommended routine osteoporosis screening for women aged 65 years or older. However, studies have indicated that osteoporosis remains underdiagnosed, and various methods such as the use of health information technology have been tried to increase screening rates. We investigated whether we could boost the low rates of bone mineral density testing with implementation of a point‐of‐care clinical decision support system in our primary care practice.

Methods  We retrospectively reviewed the medical records of female patients eligible for osteoporosis screening who had no prior bone mineral density test who were seen at our primary care practice sites in 2007 or 2008 (before and after implementation of a point‐of‐care clinical decision support system).

Results  Overall, screening rates were 80.1% in 2007 and 84.1% in 2008 (P < 0.001). Of patients who did not have osteoporosis screening before the visit, 5.87% completed the screening after the visit in 2007, compared with 9.79% in 2008 (when the clinical support system was implemented), a 66.7% improvement (P = 0.025).

Conclusion  Clinical decision support for primary care doctors significantly improved osteoporosis screening rates among eligible women. Carefully designed clinical decision support systems can optimize care delivery, ensuring that important preventive services such as osteoporosis screening for patients at risk for fracture are performed while unnecessary testing is avoided.
Gonial angles and condylar and ramus height of the mandible in complete denture wearers—a panoramic radiograph study
Authors: RAUSTIA A.M. , SALONEN M.A.M.
Published: August 2010

summary
It has been accepted that the shape of the mandibular base, and especially the gonial angle of the mandible, correlates with the function of the jaw closing muscles. The gonial angles of the mandible and condylar and ramus heights of 30 complete denture wearers (18 women, 12 men, mean age 61 years, range 42–74 years) coming for renewal of their dentures were measured using panoramic radiographs. The mean period of edentulousness was 26 years (range 10–53 years). No statistically significant difference was observed between the sexes in the the sizes of gonial angles and condylar and ramus heights. The right gonial angle was statistically significantly smaller than the left one and correlated negatively with the ramus height in both sides but positively with the increased EMG activity in the right masseter muscle. The size of the gonial angle and the condylar and ramus heights did not correlate with the age of the patients, edentulous period or alveolar ridge resorption.
Evidence for dental and dental specialty treatment of obstructive sleep apnoea. Part 1: the adult OSA patient and Part 2: the paediatric and adolescent patient
Authors: CONLEY R. S.
Published: August 2010

Summary  Until recently, obstructive sleep apnoea was a largely unknown condition. Because of the well‐publicised death of some high‐profile people resulting from untreated obstructive sleep apnoea, now mostly everyone has heard of the condition. Following diagnosis, several medical treatment modalities are available to patients. However, the role that dentistry and its various specialties can play in successful treatment for obstructive sleep apnoea should not be overlooked. The common causes for adult and paediatric obstructive sleep apnoea will be presented as well as a review of the more successful forms of dental treatment. Finally, a summary of the current evidence regarding obstructive sleep apnoea treatment will be presented.
Cell division in a minimal bacterium in the absence of ftsZ
Authors: Lluch‐Senar Maria , Querol Enrique , Piñol Jaume
Published: August 2010

Mycoplasma genomes exhibit an impressively low amount of genes involved in cell division and some species even lack the ftsZ gene, which is found widespread in the microbial world and is considered essential for cell division by binary fission. We constructed a Mycoplasma genitalium ftsZ null mutant by gene replacement to investigate the role of this gene and the presence of alternative cell division mechanisms in this minimal bacterium. Our results demonstrate that ftsZ is non‐essential for cell growth and reveal that, in the absence of the FtsZ protein, M. genitalium can manage feasible cell divisions and cytokinesis using the force generated by its motile machinery. This is an alternative mechanism, completely independent of the FtsZ protein, to perform cell division by binary fission in a microorganism. We also propose that the mycoplasma cytoskeleton, a complex network of proteins involved in many aspects of the biology of these microorganisms, may have taken over the function of many genes involved in cell division, allowing their loss in the regressive evolution of the streamlined mycoplasma genomes.
Regulated maturation of malaria merozoite surface protein‐1 is essential for parasite growth
Authors: Child Matthew A. , Epp Christian , Bujard Hermann , Blackman Michael J.
Published: August 2010

The malaria parasite Plasmodium falciparum invades erythrocytes where it replicates to produce invasive merozoites, which eventually egress to repeat the cycle. Merozoite surface protein‐1 (MSP1), a prime malaria vaccine candidate and one of the most abundant components of the merozoite surface, is implicated in the ligand–receptor interactions leading to invasion. MSP1 is extensively proteolytically modified, first just before egress and then during invasion. These primary and secondary processing events are mediated respectively, by two parasite subtilisin‐like proteases, PfSUB1 and PfSUB2, but the function and biological importance of the processing is unknown. Here, we examine the regulation and significance of MSP1 processing. We show that primary processing is ordered, with the primary processing site closest to the C‐terminal end of MSP1 being cleaved last, irrespective of polymorphisms throughout the rest of the molecule. Replacement of the secondary processing site, normally refractory to PfSUB1, with a PfSUB1‐sensitive site, is deleterious to parasite growth. Our findings show that correct spatiotemporal regulation of MSP1 maturation is crucial for the function of the protein and for maintenance of the parasite asexual blood‐stage life cycle.
Purine restriction induces pronounced translational upregulation of the NT1 adenosine/pyrimidine nucleoside transporter in Leishmania major
Authors: Ortiz Diana , Valdés Raquel , Sanchez Marco A. , Hayenga Johanna , Elya Carolyn , Detke Siegfried , Landfear Scott M.
Published: August 2010

Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1‐NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gene resulted in pronounced upregulation of adenosine and uridine uptake mediated by the NT1 permease and also induced up to a 200‐fold enhancement in the level of the NT1 protein but not mRNA. A similar level of upregulation of NT1 was achieved in wild‐type promastigotes that were transferred to medium deficient in purines. Pulse labelling and treatment of cells with the translation inhibitor cycloheximide revealed that control of NT1 expression occurs primarily at the level of translation and not protein turnover. These observations imply the existence of a translational control mechanism that enhances the ability of Leishmania parasites to import essential purines when they are present at limiting concentrations.
Validation of a Fully Automated Analysis of Esophageal Body Contractility and Lower Esophageal Sphincter Function: A Study on the Effect of the PGEI Analogue Rioprostil on Human Esophageal Motility
Authors: Tijskens G. , Janssens J. , Vantrappen G. , De Bondt F.
Published: August 2010

A new method for automatic analysis of resting lower esophageal sphincter pressure and postdeglutitive motor activity of esophageal body and lower esophageal sphincter (LES) is validated by comparing the results obtained with automatic and manual analysis of 11,700 esophageal body pressure peaks, 390 resting LES pressure measurements, and 3900 LES relaxations. The automatic analysis is based on the on‐line transformation of pressure recordings into a mathematical formula using B‐spline functions, which allows one to use the same parameters as those generally applied in manual analysis of esophageal manometric recordings. Statistical evaluation of the results indicates that this method provides a faithful analysis of the pressure tracings. The difference between manual and automatic analysis (mean ± SD) was only + 1.49 ± 4.26 mm Hg for wave amplitude, ‐0.15 ± 0.61 seconds for wave duration, +0.37 ± 1.05 cm/second for progression velocity, +0.95 ± 1.38 mm Hg for resting LES pressure, and ‐2.0 ± 1.67 mm Hg for residual LES pressure after deglutition. Wave form was correctly recognized in 95.3% of the waves. Pressure recordings were obtained from a study on the effect of the PGE1 analogue rioprostil (600 and 300 μg), administered orally on esophageal motor function in 10 normal volunteers. The drug increased both the resting LES pressure and the amplitude of esophageal body contractions and decreased the completeness of LES relaxation after swallowing.
Structure‐Activity Relation of Erythromycin‐Related Macrolides in Inducing Contractions and in Displacing Bound Motilin in Rabbit Duodenum
Authors: Depoortere I. , Peeters T. L. , Matthijs G. , Cachet T. , Hoogmartens J. , Vantrappen G.
Published: August 2010

ERYTHROMYCIN A appears to be a motilin agonist, although motilin (a peptide) and erythromycin A (a 14‐member macrolide antibiotic carrying two sugar substituents) are structurally totally unrelated. To obtain information concerning the structural requirements for erythromycin's interaction with the motilin receptor, we studied 60 derivatives and seven fragments of erythromycin, and six macrolides with a 16‐member ring structure. For every compound the ability to displace motilin bound to a crude homogenate of rabbit antral smooth muscle tissue and the ability to induce contractions in rabbit duodenal segments were determined. For both parameters dose‐response curves were obtained, and the negative logarithms of the concentrations inhibiting 50% of the binding (pIC‐50) or inducing 50% of the maximum response to a maximal contractile dose of acetylcholine (pEC‐50) were determined. All macrolides with a 16‐member ring structure were inactive in both types of experiments. In all erythromycin derivatives variations of the ring structure had a marked effect. For both parameters the order of potency was enol ether > pseudo–enol ether > parent ring > pseudo‐hemiketal > anhydro. The two sugars attached to the ring were important too, because removing either or both of them resulted in an inactive compound. Modifications of the dimethylamino group of the desosamine sugar affect the potency, while the orientation of the cladinose moiety seems to be important too. For all active compounds, both parameters studied were well correlated (r= 0.80, p < 0.001). Our results support the concept that erythomycin‐like macrolides are motilin agonists. The structural requirements of these “motilides” involve the ring structure, especially the part that can be transformed into an enol ether, and both attached sugars. Potent derivatives may prove to be useful as gastrokinetic agents with a very specific target zone.
Regulation of Gastric Corpus Tone by the Vagus Nerve in the Ferret
Authors: Grundy D. , Naseri M. K. Gharib , Hutson D.
Published: August 2010

The pressure‐volume relationship of the ferret gastric corpus was investigated to quantify the relative contributed of cholinergic and nonadrenergic, noncholinergic (NANC) mechanisms to the volume‐accommodating property of this region. In splanchnectomized animals under control conditions the pressure‐volume relationship of the corpus fitted a linear regression (Y = 0.30X + 0.57). Atropine decreased the magnitude of the pressure rise per unit volume, while after vagotomy this effect was reversed. The magnitude of these pressure changes in individual animals was consistent with reciprocal regulation of cholinergic and NANC pathways. Moreover, after vagotomy the shape of the pressure‐volume curve was altered such that the pressure rise per unit volume was greater at the lower distending volumes. Continuous, low‐frequency electrical vagal stimulation restored the pressure‐volume relationship to that seen prior to vagotomy, an effect abolished by hexamethonium (25 mg/kg). Vasoactive intestinal polypeptide, on the other hand, caused a dose‐related reduction in corpus pressure during the ramp increases in volume comparable to that seen during electrical stimulation but did not restore the shape of the pressure‐volume curve. These data indicate that the action of the vagus may in part be permissive, with the sensitivity of local NANC pathways being modulated by a vagal cholinergic input.
Change in Intracellular Cyclic Nucleotide Content Accompanies Relaxation of the Isolated Canine Internal Anal Sphincter
Authors: Grous Marilyn , Joslyn Alan F. , Thompson Winston , Barnette Mary S.
Published: August 2010

Changes in cyclic nucleotide content arc associated with relaxation of lower esophageal sphincter (LES) smooth muscle. Although agents that increase cyclic AMP (cAMP) or cyclic CMP (cGMP) can relax the LES, relaxation produced by activation of enteric neurons is associated with, an increase in intracellular cGMP. To evaluate these changes in another sphincteric area of the gut, ice determined the effects of electrical field stimulation (EFS) (65 V, I ms) and of several relaxant agents that alter cyclic nucleotide content in isolated strips of canine internal anal sphincter. Each strip was contracted with norepinephrine (3 μM). During maximum contraction, tissues were relaxed by EFS or by addition of relaxant agents. EFS produced, a frequency‐related relaxation, accompanied by a significant, increase, in cGMP; however, cAMP increased only slightly at the maximum frequency tested (8 Hz). Both EFS‐induced relaxation and increased cGMP content were blocked 1 μM tetrodotoxin. Cumulative addition of sodium nitroprusside, forskolin, 8‐bromoguanosine 3',5'‐cylic monophosphate, or 8‐bromoadenosine 3',5'‐cyclic monophosphate relaxed the internal anal sphincter in a concentration‐dependent manner. Sodium nitroprusside‐induced relaxations were accompanied by concentration‐dependent increases in cGMP content, whereas forskolin‐induced relaxations were accompanied by concentration‐dependent increases in cAMP content. In conclusion, both cAMP and cCMP appear to be intracellular mediators of relaxation in the canine internal anal sphincter. In addition, relaxation produced by activation of intrinsic inhibitory neurons is associated with an elevation of intracellular cGMP. Together with our previous findings in the LES, these results suggest that cCMP may be the intracellular mediator of neuronally induced, relaxation of gut sphincteric regions.
Progressive muscular relaxation and motility of the small intestine: studies in normal subjects and patients with irritable bowel syndrome
Authors: KELLOW J. E. , LANGELUDDECKE P. M. , ECKERSLEY G. M. , JONES M. P. , TENNANT C. C.
Published: August 2010

Recordings of fasting duodenojejunal motor activity were obtained during a controlled 20‐min period of psychological relaxation in 10 patients with irritable bowel syndrome (IBS) and 10 healthy subjects. The IBS group showed a significant decline in their level of arousal (on both cardiovascular and subjective measures) in response to relaxation; such alterations were minimal in the control group. Both groups, however, demonstrated significant inhibition of phase 2 activity (motility index, contractile frequency and amplitude) of the migrating motor complex in response to relaxation, and the magnitude of the response did not differ between the two groups. Clustered contractile activity present in 4 IBS patients was also suppressed during the relaxation period. There were no correlations between changes in the level of arousal and the degree of motor suppression in either IBS patients or controls. These findings demonstrate that psychological relaxation therapy can profoundly influence patterns of small bowel motility, and shed light on the mechanisms by which psychological intervention therapy appears to be effective in IBS.
Yohimbine stimulates colonic motility through a central action in conscious dogs
Authors: FIORAMONTI J. , BERLAN M. , FARGEAS M. J. , BUENO L.
Published: August 2010

The effects of the α2‐adrenoceptor antagonist yohimbine on colonic motility were examined before and after vagotomy in conscious dogs chronically fitted with strain gauge transducers on the proximal, transverse and distal colon, and a cannula placed in a lateral ventricle of the brain. They were compared to those of another α2‐adrenoceptor antagonist, SKωF 86466, which poorly crosses the blood‐brain barrier. Intravenous administration of yohimbine (0.2 mg/kg) stimulated the motility of the proximal and transverse colon, the motility index being increased for the first hour by 59 and 55%, respectively, in comparison with controls. No significant increase in motility index was observed on the distal colon. After vagotomy the effects of intravenous yohimbine were limited to 1 to 3 high amplitude contractions. Intracerebroventricular administration of yohimbine (20 μg/kg) reproduced the effects of intravenous administration and was ineffective after vagotomy. Intracerebroventricular but not intravenous administration of SKωF 86466 stimulated the motility of the proximal and transverse colon; this effect was also abolished after vagotomy. It is concluded that yohimbine stimulates colonic motility through a blockade of central α2‐adrenoceptor and that these effects are mediated by the vagus.
Prostaglandin E2(PGE2)‐evolted chloride secretion in guinea‐pig colon is mediated by nerve‐dependent and nerve‐independent mechanisms
Authors: FRIELING T. , RUPPRECHT C. , DOBREVA G. , SCHEMANN M.
Published: August 2010

AbstractConventional flux chamber and intracellular recording methods were used to investigate the effect of prostaglandin E2on ion transport and on electrical behaviour of submucosal neurones in guinea‐pig colon. In flux chamber experiments, prostaglandin E2evoked a dose‐dependent increase in short‐circuit current. The response was reduced by serosal addition of bumetanide, tetrodotoxin or atropine, but not hexamethonium or piroxicam. This indicates that the response to prostaglandin E2was mediated in part by activation of chloride secretion via submucosal neurons. Application of prostaglandin E2to submucosal neurones evoked a depolarization of the membrane potential associated with an enhanced spike discharge which was frequently triggered by fEPSPs. The depolarizing response to prostaglandin E2was not affected by tetrodotoxin, indicative of a direct effect of prostaglandin E2on the impaled neurones. However, the increased spike activity was synaptically driven suggesting an additional activation of other cells. Prostaglandin E2had no excitatory or inhibitory effect on cholinergic fast excitatory postsynaptic potentials. The study suggests that prostaglandin E2may function as a neuromodulator to evoke nerve‐mediated chloride secretion through activation of submucosal neurones. The results further indicate that prostaglandin E2may influence mucosal function by altering electrical behaviour of submucosal neurones leading to spread of excitation throughout the plexus.
Microbially mediated carbonate precipitation in a hypersaline lake, Big Pond (Eleuthera, Bahamas)
Authors: GLUNK CHRISTINA , DUPRAZ CHRISTOPHE , BRAISSANT OLIVIER , GALLAGHER KIMBERLEY L. , VERRECCHIA ERIC P. , VISSCHER PIETER T.
Published: August 2010

Microbial metabolism impacts the degree of carbonate saturation by changing the total alkalinity and calcium availability; this can result in the precipitation of carbonate minerals and thus the formation of microbialites. Here, the microbial metabolic activity, the characteristics and turnover of the extracellular polymeric substances and the physicochemical conditions in the water column and sediments of a hypersaline lake, Big Pond, Bahamas, were determined to identify the driving forces in microbialite formation. A conceptual model for organomineralization within the active part of the microbial mats that cover the lake sediments is presented. Geochemical modelling indicated an oversaturation with respect to carbonates (including calcite, aragonite and dolomite), but these minerals were never observed to precipitate at the mat–water interface. This failure is attributed to the capacity of the water column and upper layers of the microbial mat to bind calcium. A layer of high Mg‐calcite was present 4 to 6 mm below the surface of the mat, just beneath the horizons of maximum photosynthesis and aerobic respiration. This carbonate layer was associated with the zone of maximum sulphate reduction. It is postulated that extracellular polymeric substances and low molecular weight organic carbon produced at the surface (i.e. the cyanobacterial layer) of the mat bind calcium. Both aerobic and anaerobic heterotrophic microbes consume extracellular polymeric substances (each process accounting for approximately half of the total consumption) and low molecular weight organic carbon, liberating calcium and producing inorganic carbon. The combination of these geochemical changes can increase the carbonate saturation index, which may result in carbonate precipitation. In conclusion, the formation and degradation of extracellular polymeric substances, as well as sulphate reduction, may play a pivotal role in the formation of microbialites both in marine and hypersaline environments.
Pre‐operative dietary restriction is feasible in live‐kidney donors
Authors: van Ginhoven Tessa M. , de Bruin Ron W.F. , Timmermans Marijke , Mitchell James R. , Hoeijmakers Jan H.J. , IJzermans Jan N.M.
Published: August 2010

van Ginhoven TM, de Bruin RWF, Timmermans M, Mitchell JR, Hoeijmakers JHJ, IJzermans JNM. Preoperative dietary restriction is feasible in live kidney donors. Clin Transplant 2011: 25: 486–494. © 2010 John Wiley & Sons A/S.

Abstract:  Dietary restriction (DR), defined as reduced energy intake without malnutrition, confers protection against renal ischemia and reperfusion injury in animal models. This pilot study investigates for the first time the feasibility of pre‐operative DR in the clinical setting. Live‐kidney donors were randomized between pre‐operative DR or ad libitum intake. Seventeen participants were instructed to follow a 30% calorie‐restricted diet, followed by one day of water‐only fasting prior to surgery. Thirteen participants were allowed to eat ad libitum pre‐operatively. Ninety‐four percent of the donors adhered to the diet, 31.4% reduction in caloric intake was achieved. Post‐operative well‐being, appetite and ability to perform daily tasks were not different between both groups. There was no difference in post‐transplant graft function of kidneys obtained from DR donors or control donors as determined by serum creatinine levels during the first post‐operative month and renograms at post‐operative day one. This study shows that mild dietary restriction is feasible in the setting of live‐kidney donation. No effect was observed regarding post‐operative graft function. Additional studies are warranted to investigate the appropriate regimen of dietary restriction to protecting against ischemia and reperfusion injury, such as increasing the magnitude and/or duration of the reduction in daily caloric intake.
Functioning and disability in bipolar disorders: a systematic review of literature using the ICF as a reference
Authors: Ávila Carolina C , Cabello María , Cieza Alarcos , Vieta Eduard , Ayuso‐Mateos José Luis
Published: August 2010

Ávila CC, Cabello M, Cieza A, Vieta E, Ayuso‐Mateos JL. Functioning and disability in bipolar disorders: a systematic review of literature using the ICF as a reference. Bipolar Disord 2010: 12: 473–482. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  To systematically identify and examine the frequency of use of concepts contained in outcome variables across bipolar disorder (BD) studies using the International Classification of Functioning, Disability and Health (ICF) as a reference.

Methods:  Original studies published between 2000 and 2006 were located on the MEDLINE and PsycINFO databases and selected according to predetermined criteria. Outcome variables were extracted, and concepts contained therein were linked to the ICF.

Results:  A total of 109 final studies were included. The concepts contained in these studies were linked to 145 different ICF categories. ICF category b152, emotional functions, was the most frequently represented category, appearing in 94% of the publications, followed by b126, temperament and personality functions (73%). E110, products or substances for personal consumption, and e580, health services, systems, and policies, appeared in 68% of the studies.

Conclusions:  The present systematic review reflects the research focus of the literature on BD in recent years. Most of the studies performed concentrate on body functions rather than activities and participation domains. Experimental studies are mostly pharmacological, reflecting the need to study nonpharmacological interventions. Furthermore, our study shows that outcome variables used in studies with persons with BD can, to a large extent, be mapped to the ICF.
Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence
Authors: López‐Jaramillo Carlos , Lopera‐Vásquez Juan , Gallo Aurora , Ospina‐Duque Jorge , Bell Vaughan , Torrent Carla , Martínez‐Arán Anabel , Vieta Eduard
Published: August 2010

López‐Jaramillo C, Lopera‐Vásquez J, Gallo A, Ospina‐Duque J, Bell V, Torrent C, Martínez‐Arán A, Vieta E. Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disord 2010: 12: 557–567. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To determine if the repeated occurrence of manic episodes in bipolar I disorder (BD‐I) patients is associated with reduced cognitive performance, which could in turn imply a worsening in the disorder’s evolution.

Method:  Cognitive performance in euthymic patients was assessed using attention, memory, and executive function tests on 24 BD‐I patients who had experienced only 1 manic episode, on 27 BD‐I patients with 2 manic episodes, on 47 BD‐I patients with 3 or more manic episodes, and on 66 healthy control subjects.

Results:  In BD‐I patients, number of manic episodes was positively associated with poorer performance on neurocognitive tests, an association that was not accounted for by depression, disease chronicity, onset, or medication. Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more.

Conclusion:  The number of manic episodes predicted poor cognitive performance, suggesting that the recurrence of mania may have a long‐term neuropsychological impact. Prospective follow‐up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function.