bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hypouricaemic and hyperuricaemic drugs on the renal urate efflux transporter, multidrug resistance protein 4
Authors: El‐Sheikh A A K , Van Den Heuvel J J M W , Koenderink J B , Russel F G M 
Published: August 2008

Background and purpose:The xanthine oxidase inhibitors allopurinol and oxypurinol are used to treat hyperuricaemia, whereas loop and thiazide diuretics can cause iatrogenic hyperuricaemia. Some uricosuric drugs and salicylate have a bimodal action on urate renal excretion. The mechanisms of action of these hypo‐ and hyperuricaemic drugs on the handling of urate in renal tubules have not been fully elucidated. Recently, we identified the multidrug resistance protein (MRP) 4 as a luminal efflux transporter for urate in the proximal tubule.Experimental approach:Here, we studied the effect of these drugs on [14C]urate transport using human embryonic kidney 293 cells overexpressing human MRP4 and in membrane vesicles isolated from these cells.Key results:Allopurinol stimulated MRP4‐mediated cellular urate efflux and allopurinol and oxypurinol both markedly stimulated urate transport by MRP4 in membrane vesicles. Bumetanide and torasemide had no effect, whereas furosemide, chlorothiazide, hydrochlorothiazide, salicylate, benzbromarone and sulfinpyrazone inhibited urate transport, at concentrations ranging from nanomolar up to millimolar. Probenecid stimulated urate transport at 0.1 μMand inhibited transport at higher concentrations.Conclusions and implications:These data suggest that inhibition of MRP4‐mediated urate efflux by furosemide and thiazide diuretics could have an important function in their hyperuricaemic mechanisms. Furthermore, stimulation of MRP4‐mediated renal urate efflux could be a new mechanism in the hypouricaemic action of allopurinol and oxypurinol. In conclusion, MRP4 may provide a potential target for drugs affecting urate homoeostasis, which needs to be further evaluatedin vivo.British Journal of Pharmacology(2008)155, 1066–1075; doi:10.1038/bjp.2008.343; published online 25 August 2008
Role of AQP2 during apoptosis in cortical collecting duct cells
Authors: Flamenco Pilar , Galizia Luciano , Rivarola Valeria , Fernandez Juan , Ford Paula , Capurro Claudia 
Published: August 2008

Background information. A major hallmark of apoptosis is cell shrinkage, termed apoptotic volume decrease, due to the cellular outflow of potassium and chloride ions, followed by osmotically obliged water. In many cells, the ionic pathways triggered during the apoptotic volume decrease may be similar to that observed during a regulatory volume decrease response under hypotonic conditions. However, the pathways involved in water loss during apoptosis have been largely ignored. It was recently reported that in some systems this water movement is mediated via specific water channels (aquaporins). Nevertheless, it is important to identify whether this is a ubiquitous aspect of apoptosis as well as to define the mechanisms involved. The aim of the present work was to investigate the role of aquaporin‐2 during apoptosis in renal‐collecting duct cells. We evaluated the putative relationship between aquaporin‐2 expression and the activation of the ionic pathways involved in the regulatory volume response.Results. Apoptosis was induced by incubating cells with a hypertonic solution or with cycloheximide in two cortical collecting duct cell lines: one not expressing aquaporins and the other stably transfected with aquaporin‐2. Typical features of apoptosis were evaluated with different approaches and the water permeability was measured by fluorescence videomicroscopy. Our results show that the rate of apoptosis is significantly increased in aquaporin‐2 cells and it is linked to the rapid activation of volume‐regulatory potassium and chloride channels. Furthermore, the water permeability of cells expressing aquaporin‐2 was strongly reduced during the apoptotic process and it occurs before DNA degradation.Conclusions. These results let us propose that under apoptotic stimulation aquaporin‐2 would act as a sensor leading to a co‐ordinated activation of specific ionic channels for potassium and chloride efflux, resulting in both more rapid cell shrinkage and more rapid achievement of adequate levels of ions necessary to activate the enzymatic apoptotic cascade.
Three-Year Prospective Study to Improve the Management of Blood-Exposure Incidents
Authors: van Wijk Paul Th. L. , Pelk-Jongen Marianne , Wijkmans Clementine , Voss Andreas , Schneeberger Peter M. 
Published: August 2008

Objective.Throughout 2003-2005, all blood-exposure incidents registered by an expert counseling center in The Netherlands accessible by telephone 24 hours a day, 7 days a week, were analyzed to assess quality improvement in the center's management of such incidents. The expert center was established to handle blood-exposure incidents that occur both inside and outside of a hospital. Infection control practitioners carried out risk assessment, made the practical arrangements associated with managing incidents, and carried out treatment and follow-up, all in accordance with standardized procedures.Design.We analyzed the time it took for exposed individuals to report the incident, the time required to perform a human immunodeficiency virus (HIV) test for the source individual when needed, occurrence of injuries, hepatitis B (HBV) vaccination status of exposed individuals, and adherence to protocol at the expert center.Results.A mean of 465 incidents was registered during each year of the 3-year study period. Although 698 (50%) of 1,394 reported exposures took place in a hospital, 704 (50%) took place outside of a hospital, and 460 (33%) occurred at a time other than regular office hours. HIV tests for source individuals were performed increasingly quickly over the course of the 3-year study period because of earlier reporting and improvements in practical matters associated with performing and processing the tests. The percentage of healthcare workers employed outside a hospital who were vaccinated against HBV increased from 34% (52 of 152) to 70% (119 of 170) during the 3-year study period. Consequently, the administration of immunoglobulin and unnecessary laboratory testing were reduced. In assessing the quality of the expert center, flaws in the handling of incidents were identified in 148 (37%) of 396 incidents analyzed in 2003, compared with 38 (8%) of 461 incidents analyzed in 2005.Conclusions.The practical matters associated with management of blood-exposure incidents, such as timely reporting and administration of prophylaxis, should be optimized for incidents that occur at times other than regular office hours and outside of hospitals. The establishment of a 24-hour centralized counseling facility that was open 7 days a week to manage blood exposures resulted in significant improvements in incident management and better care.
Seasonal shifts in the diet of lake zooplankton revealed by phospholipid fatty acid analysis
Authors: TAIPALE SAMI , KANKAALA PAULA , HÄMÄLÄINEN HEIKKI , JONES ROGER I. 
Published: August 2008

Summary1. We analysed the phospholipid fatty acid (PLFA) profiles of seston and of the dominant zooplankter, Daphnia longispina, through the open water period in a small, dystrophic lake to investigate seasonal variation in the diet of Daphnia. Phytoplankton, heterotrophic bacteria, green sulphur bacteria and methane‐oxidizing bacteria (MOB) were all present in the water column of the lake, and previous studies have indicated that vertically migrating Daphnia can exploit all these potential food sources.2. For adult Daphnia, although there was some correspondence between the PLFA profile of Daphnia and the concurrent seston PLFA profile, strongest correlations were between the Daphnia PLFA profile and those of potential food sources determined 7 days earlier. This interval presumably reflects the time it takes for adult Daphnia to turn over their fatty acid pool.3. A correlation between the concentration of polyunsaturated fatty acids (PUFAs) in the epi‐ and metalimnion and measured primary production indicated that, within the total PLFA fraction, PUFAs can be useful biomarkers for phytoplankton in food‐web studies. Algal PUFAs contributed appreciably to total PLFAs in adult Daphnia during spring and summer, but less so in autumn.4.  Daphnia in the lake actually reached their highest biomass in autumn, when methanotrophic activity was also highest, and the highest magnitude of MOB‐specific PLFAs was recorded in both adult and juvenile Daphnia. A strong relationship existed between δ13C values of Daphnia reported previously and the proportion of MOB‐specific PLFAs in Daphnia. Autumnal mixing evidently stimulates bacterial oxidation of methane from the hypolimnion, and exploitation of the methanotrophic bacteria sustains a high Daphnia population late in the season.5. Our results show that the PLFA composition of freshwater zooplankton like Daphnia corresponds rather well to that of their in situ diet of phytoplankton and bacteria, with a lag period of around 1 week in the case of adult animals. The PLFA profile of seston revealed the dominant available food sources, and relating these to the Daphnia PLFA profile provided insights into seasonal changes in Daphnia diet.
Drainage ditching at the catchment scale affects water quality and macrophyte occurrence in Swedish lakes
Authors: ECKE FRAUKE 
Published: August 2008

Summary1. We have limited knowledge of the effects of land use in general and of drainage ditching in particular on macrophyte communities in lakes. I quantified catchment land use, including drainage ditching, as well as water quality and the number of macrophyte species in 17 Swedish lakes in summer 2005.2. Land use within 1 km of the studied lakes was analysed in a geographic information system. The following variables were included: areas of forests, mires, agricultural land and urbanization, length of drainage ditches (classified according to the use of the land they drained), and shortest distance from lake to an urban area. To extract and analyse general trends in the data sets, redundancy analysis was used.3. Water quality was explained mainly by three land‐use related variables: the lengths of agricultural, forest and mire ditches. The length of agricultural ditches was positively correlated with lake water conductivity, total dissolved solids, Ca, N and total organic carbon (TOC). The lengths of forest and mire ditches were positively correlated with lake water characteristics, especially TOC.4. The number of species representing different macrophyte life forms was explained by three environmental variables: conductivity, and lengths of forest and agricultural ditches. The numbers of isoetids, nymphaeids, elodeids and total obligate hydrophytes were negatively correlated with length of forest ditches. In contrast, the number of lemnids and helophytes was positively correlated with conductivity and length of agricultural ditches. Furthermore, the number of isoetids was exponentially related (negatively) to lengths of agricultural and forest ditches, indicating a threshold response to drainage ditch length.5. The results suggest that effects on water quality and macrophyte communities result from drainage ditching in the lake catchments rather than from land use itself. Given the total area of drainage‐ditched land worldwide (millions of ha in Scandinavia alone), drainage ditching should be considered when evaluating environmental impacts on lake water quality and macrophyte occurrence and when determining reference conditions for catchment land use.
Retracted: Manuka honey vs. hydrogel – a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers
Authors: Gethin Georgina , Cowman Seamus 
Published: August 2008

Objective.  Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg ulcers treated with Manuka honey (Woundcare 18+) vs. standard hydrogel therapy (IntraSite Gel).Background.  Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of a randomised controlled trial is not available. There is a paucity of research which uses Manuka honey in venous ulcers.Design.  Prospective, multicentre, open label randomised controlled trial.Method.  Randomisation was via remote telephone. One hundred and eight patients with venous leg ulcers having ≥50% wound area covered in slough, not taking antibiotics or immunosuppressant therapy were recruited from vascular centres, acute and community care hospitals and leg ulcer clinics. The efficacy of WoundCare 18+ to deslough the wounds after four weeks and its impact on healing after 12 weeks when compared with IntraSite Gel control was determined. Treatment was applied weekly for four weeks and follow‐up was made at week 12.Results.  At week 4, mean % reduction in slough was 67% WoundCare 18+ vs. 52·9% IntraSite Gel (p = 0·054). Mean wound area covered in slough reduced to 29% and 43%, respectively (p = 0·065). Median reduction in wound size was 34% vs. 13% (p = 0·001). At 12 weeks, 44% vs. 33% healed (p = 0·037). Wounds having >50% reduction in slough had greater probability of healing at week 12 (95% confidence interval 1·12, 9·7; risk ratio 3·3; p = 0·029). Infection developed in 6 of the WoundCare 18+ group vs. 12 in the IntraSite Gel group.Conclusion.  The WoundCare 18+ group had increased incidence of healing, effective desloughing and a lower incidence of infection than the control. Manuka honey has therapeutic value and further research is required to examine its use in other wound aetiologies.Relevance to clinical practice.  This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous ulcers. Additionally, effective desloughing significantly improves healing outcomes.
Effect of iron or multiple micronutrient supplements on the prevalence of anaemia among anaemic young children of a malaria‐endemic area: a randomized double‐blind trial
Authors: Ouédraogo Hermann Z. , Dramaix‐Wilmet Michèle , Zeba Augustin N. , Hennart Philippe , Donnen Philippe 
Published: August 2008

SummaryObjective  To assess the effect of supplementation with iron or multiple micronutrients (MM) on the prevalence of anaemia in a malaria‐endemic area.Methods  A community‐based randomized double‐blind trial was conducted in rural Burkina Faso, including children aged 6–23 months with haemoglobin (Hb) concentrations of 70–109 g/l who were randomized into an iron group (Fe, n = 96), an iron and zinc group (IZ, n = 100) or an MM group (MM, n = 100), 5 days/week for 6 months. All children were provided with insecticide‐treated bednets; those who had a Plasmodium falciparum (PF) positive‐smear at baseline and/or at each monthly checking received antimalarial therapy.Results  The mean (SD) endpoint Hb concentration was higher in the MM group [113.2 (13.6) g/l] than in the IZ group [106.3 (15.6) g/l] and the Fe group [107.1 (12.9) g/l] (P = 0.001). Children in the MM group were more likely to recover from anaemia than those in the Fe group [prevalence rate ratios, PRR (95% confidence interval, CI) = 1.62 (1.22–2.15), P < 0.001]. The IZ group did not differ from the Fe group [PRR (95% CI) = 0.94 (0.65–1.35), P = 0.72]. None of the interactions on the effect of supplementation of baseline age (0.13), or baseline height‐for‐age z‐score (P = 0.33), or incident PF parasitemia (P = 0.99), was significant.Conclusion  In this malaria‐endemic area, in combination with malaria management, the MM supplement was more efficacious than the Fe supplement and the IZ supplement for reducing anaemia. Further investigation into limiting factors and amounts of micronutrients that would be more efficacious for reducing anaemia is recommended.
Drug regimens for visceral leishmaniasis in Mediterranean countries
Authors: Gradoni Luigi , Soteriadou Ketty , Louzir Hecmi , Dakkak Allal , Toz Seray Ozensoy , Jaffe Charles , Dedet Jean‐Pierre , Campino Lenea , Cañavate Carmen , Dujardin Jean‐Claude 
Published: August 2008

SummaryUntil the early 1990s, pentavalent antimony was the only documented first‐line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re‐evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium (‘LeishMed’ network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid‐associated amphotericin B (AmB) formulations are used as first‐line drugs, although in different patients’ categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (≥95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country’s wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient’s care.
The effect of chronic variable stress on bowel habit and adrenal function in rats
Authors: Kim Yong S , Lee Moon Y , Choi Chang S , Sohn Young W , Park Byung R , Choi Myung‐Gyu , Nah Yong‐Ho , Choi Suck C 
Published: August 2008

AbstractBackground and Aim:  Increased colonic motility is a well‐known stress response and corticotropin releasing hormone plays an important role in this response, but sequential change of bowel habit and adrenal function during chronic stress has not been reported. The objective of this study was to evaluate the effect of chronic stress on bowel habit and adrenal function.Methods:  Male Sprague‐Dawley rats were exposed to chronic variable stress (CVS) for 6 weeks. We measured daily the number and weight of pellets and weekly urinary corticosterone. After 6 weeks of experiment, visceromotor response (VMR) to colorectal distention (CRD), serum corticosterone and adrenal glands weight were measured.Results:  The number and weight of pellets in CVS rats was greater than those of the control rats initially and decreased during the later period. However, CVS rats showed continuously exaggerated daily variation of pellet number than control rats to the end of experimental period. Urinary corticosterone was increased in CVS rat until the fifth week, but urine and serum corticosterone were not statistically different between groups at the sixth week. However, the relative weight of adrenal glands was higher in CVS rats at the sixth week. CVS rats showed exaggerated VMR to CRD than the control rats.Conclusions:  The prolonged and variable stress to rats induced sustained bowel habit dysfunction and visceral hypersensitivity without adaptation. Chronic stress also increased adrenal activity from the early phase and finally caused adrenal hypertrophy with relatively decreased activity. But adrenal change was not parallel to bowel habit change and it remains to be seen whether adrenal dysfunction is directly related to bowel habit dysfunction.
Comparison of four current staging systems for Chinese patients with hepatocellular carcinoma undergoing curative resection: Okuda, CLIP, TNM and CUPI
Authors: Lu Wenping , Dong Jiahong , Huang Zhiqiang , Guo Deyu , Liu Yousheng , Shi Shuang 
Published: August 2008

AbstractBackground and Aim:  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, there is no general consensus as to which staging system is the most reliable for predicting the survival of patients with HCC. The aims of this study were to compare commonly‐used staging systems in a cohort of Chinese HCC patients undergoing curative resection.Methods:  From January 1991 to June 2002, 234 Chinese patients undergoing curative resection for HCC from one medical center were evaluated. All patients were classified by the Okuda, Cancer of the Liver Italian Program (CLIP), tumor node metastasis (TNM) (6th edition) and the Chinese University Prognostic Index (CUPI) staging systems. Survival curves were calculated using the Kaplan–Meier method and were examined using log‐rank testing. The overall predictive power for patient survival with each staging system was evaluated by the area under the receiver operating characteristic (ROC) curve.Results:  The overall median survival of the entire cohort was 24.9 months (95% confidence interval (CI) 18.15–31.65 months) and the estimated survival rates at 1, 3, and 5 years were 69.66% ± 3.01%, 41.02% ± 3.31%, and 29.08% ± 3.55%, respectively. In our patient cohort, the log‐rank test demonstrated that the TNM and Okuda staging systems gave better results than the other staging systems in the prognosis stratification. The prognostic predictive powers of the TNM staging for survival, evaluated by ROC curve areas, was also superior.Conclusions:  For HCC patients undergoing curative resection, the TNM staging system (6th edition) proved the best for prognostic stratification and prognosis prediction.
Biochemical and molecular characterization of hepatocyte‐like cells derived from human bone marrow mesenchymal stem cells on a novel three‐dimensional biocompatible nanofibrous scaffold
Authors: Kazemnejad Somaieh , Allameh Abdolamir , Soleimani Masoud , Gharehbaghian Ahmad , Mohammadi Yousef , Amirizadeh Naser , Jazayery Maryam 
Published: August 2008

AbstractBackground:  There is significant interest in using nanofibers in tissue engineering from stem cells. The transdifferentiation of mesenchymal stem cells into the hepatic lineage in a nanofibrous structure has not been reported. In this study, a three dimensional nanofibrous scaffold is introduced for differentiation of human bone marrow derived mesenchymal stem cells (hBMSCs) into hepatocytes.Methods:  A scaffold composed of Poly (ε‐caprolactone), collagen and polyethersulfone was fabricated by the electrospinning technique. After characterization of isolated hBMSCs, the performance of the cells on the scaffold was evaluated by Scanning Electron Microscopy (SEM) and MTT assay. Cytological, molecular and biochemical markers were measured to confirm differentiation potential of hBMSCs into hepatocytes.Results:  The isolated cells possessed the basic properties of mesenchymal stem cells (MSCs). Based on scanning electron microscope (SEM) analysis and MTT assay, it was shown that the cells adhere, penetrate and proliferate on the nanofibers. Cultured cells on the nanofibers differentiated into hepatocyte‐like cells and expressed hepatocyte specific markers such as albumin, α‐fetoprotein, cytokeratin‐18, cytokeratin‐19 and cytochrome P450 3A4 at mRNA levels. Appearance of a considerable number of albumin‐positive cells cultivated on the scaffold (47 ± 4%) as compared to the two‐dimensional culture system (28 ± 6%) indicates the supporting role of the scaffold. The efficiency of the cells to produce albumin, urea, transferrin, serum glutamic pyruvic transaminase and serum oxaloacetate aminotransferase in hepatocytes on the scaffold further attest to the functionality of the cells.Conclusion:  The data presented in this study show that the engineered nanofibrous scaffold is a conductive matrix which supports and enhances MSC development into functional hepatocyte‐like cells.