bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aliskiren reduces body‐weight gain, adiposity and plasma leptin during diet‐induced obesity
Authors: Stucchi Paula , Cano Victoria , Ruiz‐Gayo Mariano , Fernández‐Alfonso María S 
Published: August 2009

Background and purpose:  Overfeeding increases adipose tissue mass and leptin production and up‐regulates the renin‐angiotensin system in adipose tissue in rodents. Here, we determined the effect of chronic treatment with the renin inhibitor, aliskiren, in a model of diet‐induced obesity in mice, on: (i) body weight, adipose tissue weight and plasma leptin; (ii) food intake and caloric efficiency; and (iii) angiotensin II (Ang II) in adipose tissue.Experimental approach:  Four‐week‐old C57BL/6J mice (n= 40) received aliskiren (50 mg·kg−1·day−1; 6 weeks) by means of a subcutaneous osmotic Alzet minipump. Animals were given either a low‐fat (10% kcal from fat) or a high‐fat diet (45% kcal from fat) during this period. Food‐intake and body‐weight variation were monitored during treatment.Key results:  In addition to a decrease of plasma renin activity, aliskiren reduced body‐weight gain, adipose pads and plasma leptin concentration, independent of the diet. In adipose tissue, local concentrations of Ang II were also reduced by aliskiren.Conclusions and implications:  Aliskiren limited the gain of adiposity in young mice. This effect was not due to changes in food intake or caloric efficiency and might be related to a down‐regulation of the local renin‐angiotensin system in adipose tissue. These effects were accompanied by reduced plasma leptin levels. As Ang II favours differentiation of adipocytes, it is possible that the decreased adipose tissue was linked to changes in adipocyte size and number.
P2X purinoceptors mediate an endothelium‐dependent hyperpolarization in longitudinal smooth muscle of anterior mesenteric artery in young chickens
Authors: Alkayed F , Boudaka A , Shiina T , Takewaki T , Shimizu Y 
Published: August 2009

Background and purpose: The chicken anterior mesenteric artery contains an outer longitudinal smooth muscle layer, whose neural regulation remains to be elucidated. ATP evokes a depolarization in the smooth muscle through P2Y purinoceptors. However, there may be an additional inhibitory regulation because blockade of P2Y purinoceptors converts the depolarization to hyperpolarization. The objective of the present study was to examine the mechanism underlying this hyperpolarization.Experimental approach: Membrane potentials of longitudinal smooth muscle of the chicken mesenteric artery were recorded with a microelectrode technique. Perivascular nerves were stimulated by applying electrical field stimulation (EFS).Key results: EFS induced a hyperpolarization in preparations obtained from 5‐week‐old chickens, whereas it evoked a depolarization in those from 12‐week‐old chickens. The EFS‐evoked hyperpolarization in 5‐week‐old chickens was blocked by a non‐specific purinoceptor antagonist, suramin, and by a specific P2X purinoceptor antagonist, pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid. Desensitization of the P2X purinoceptor with its agonist α,β‐MeATP significantly suppressed EFS‐evoked hyperpolarization. Blockade of the P2Y purinoceptor did not affect EFS‐evoked hyperpolarization. The application of the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester or the removal of the endothelium inhibited the hyperpolarization. The application of the nitric oxide (NO) donor sodium nitroprusside mimicked the hyperpolarization. Reverse transcriptase‐PCR showed that P2X purinoceptors are expressed in the endothelium of the anterior mesenteric artery.Conclusions and implications: Hyperpolarization in the longitudinal smooth muscle of the chicken anterior mesenteric artery was induced by ATP. ATP released from perivascular nerves may act on P2X purinoceptors in the endothelium and thereby stimulate NO production.
Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2
Authors: Suwa A , Yamamoto T , Sawada A , Minoura K , Hosogai N , Tahara A , Kurama T , Shimokawa T , Aramori I 
Published: August 2009

Background and purpose:  The lipid phosphatase known as SH2 domain‐containing inositol 5′‐phosphatase 2 (SHIP2) plays an important role in the regulation of the intracellular insulin signalling pathway. Recent studies have suggested that inhibition of SHIP2 could produce significant benefits in treatment of type 2 diabetes. However, there were no small molecule SHIP2 inhibitors and we, therefore, aimed to identify this type of compound.Experimental approach:  The phosphatase assay with malachite green was used for high‐throughput screening. The pharmacological profiles of suitable compounds were further characterized in phosphatase assays, cellular assays and oral administration in normal and diabetic (db/db) mice.Key results:  During high‐throughput screening, AS1949490 was identified as a potent SHIP2 inhibitor (IC50= 0.62 µM for SHIP2). This compound was also selective for SHIP2 relative to other intracellular phosphatases. In L6 myotubes, AS1949490 increased the phosphorylation of Akt, glucose consumption and glucose uptake. In FAO hepatocytes, AS1949490 suppressed gluconeogenesis. Acute administration of AS1949490 inhibited the expression of gluconeogenic genes in the livers of normal mice. Chronic treatment of diabetic db/db mice with AS1949490 significantly lowered the plasma glucose level and improved glucose intolerance. These in vivo effects were based in part on the activation of intracellular insulin signalling pathways in the liver.Conclusions and implications:  This is the first report of a small molecule inhibitor of SHIP2. This compound will help to elucidate the physiological functions of SHIP2 and its involvement in various diseases, such as type 2 diabetes.
Incidence and risk factors predicting blood transfusion in caesarean section
Authors: CHUA Seng Chai , JOUNG Steven J. , AZIZ Rihdab 
Published: August 2009

Background: Routine preoperative evaluation for caesarean section (CS) has commonly included a blood type and screen evaluation due to risk of blood transfusion. However, there have been no objective local data to support such practices.Aims: To evaluate the cost‐effectiveness of blood type and screen testing for CS.Methods: This retrospective study reviewed all singleton CS at a tertiary hospital using data from Blood Bank Registry and Obstetric Database, from 1 January 2004 to 31 December 2005. Clinical variables including demographic characteristics, estimated blood loss, indications for CS, preoperative haemoglobin and indications for transfusions were gathered. All patients who had blood transfusion recorded in Obstetric Database or in Blood Bank Registry had their medical records reviewed by two reviewers to confirm accuracy and identify risk factors for haemorrhage.Results: Of 2212 patients with singleton pregnancy who underwent CS, 14 (0.63%) required a blood transfusion. The risk of blood transfusion for elective and emergency CS are 3.9 per 1000 and 9.8 per 1000, respectively. In the absence of risk factors identified in this study, no women (of a total of 1293 elective CS) required blood transfusion.Conclusion: In the absence of significant risk factors for haemorrhage at CS in a tertiary setting, routine blood type and screen testing does not enhance patient care. In the rare event that a patient without previously identifiable risk factors requires an urgent blood transfusion, O negative blood could be given in the interim pending formal determination of type and cross‐match.
Population‐based carrier screening for cystic fibrosis in Victoria: The first three years experience
Authors: MASSIE John , PETROU Vicki , FORBES Robyn , CURNOW Lisette , IOANNOU Liane , DUSART Desiree , BANKIER Agnes , DELATYCKI Martin 
Published: August 2009

Background: Cystic fibrosis (CF) is the most common inherited, life‐shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant.Aims:  To report the outcomes of a carrier screening program for CF.Method: Carrier screening was offered to women and couples planning a pregnancy, or in early pregnancy, through obstetricians and general practitioners in Victoria, Australia. Samples were collected by cheek swab and posted to the laboratory. Twelve CFTR gene mutations were tested. Carriers were offered genetic counselling and partner testing. Carrier couples were offered prenatal testing by chorionic villous sampling (CVS) if pregnant. The number of people tested, carriers detected and pregnancy outcomes were recorded from January 2006 to December 2008.Results: A total of 3200 individuals were screened (3000 females). One hundred and six carriers were identified (one per 30, 95% confidence interval one per 25, one per 36). All carrier partners were screened, and nine carrier couples identified (total carriers 115). Ninety‐six individuals (83%) were carriers of the p.508del mutation. Of the nine carrier couples, six were pregnant at the time of screening (five natural conception and one in vitro fertilisation) and all had CVS (mean gestation 12.5 weeks). Two fetuses were affected, three were carriers and one was not a carrier. Termination of pregnancy was undertaken for the affected fetuses.Conclusion: Carrier screening for CF by obstetricians and general practitioners by cheek swab sample can be successfully undertaken prior to pregnancy or in the early stages of pregnancy.
Systematic multidisciplinary approach to reporting perinatal mortality: Lessons from a five‐year regional review
Authors: KENT Alison L. , DAHLSTROM Jane E. , ELLWOOD David , BOURNE Maureen ,   for the ACT Perinatal Mortality Committee
Published: August 2009

Background:  Because of differences in reporting criteria throughout the world, comparing perinatal mortality rates and identifying areas of concern can be complicated and imprecise.Aims:  To detail the systematic approach to reporting perinatal deaths and to identify any significant differences in outcomes in the Australian Capital Territory (ACT).Methods:  Review of perinatal deaths from 2001 to 2005 in the ACT using the Australian and New Zealand Antecedent Classification of Perinatal Mortality (ANZACPM) and the Australian and New Zealand Neonatal Death Classification (ANZNDC) systems.Results:  ACT residents’ perinatal mortality rate was 10.6 per 1000 total births, fetal death rate 7.5 per 1000 total births and neonatal death rate 3.2 per 1000 live births. The three leading antecedent causes of perinatal death were congenital anomalies, spontaneous preterm birth and unexplained antepartum death. The three leading causes of neonatal death were extreme prematurity, cardiorespiratory disorders and congenital anomalies. Multiple births attributed to 20% (65 of 321) of perinatal deaths. Perinatal autopsy was performed in 50% of cases, but in only 64% of unexplained antepartum deaths.Conclusions:  Causes of perinatal death for the ACT and surrounding New South Wales region are similar to other states using this classification system. The following are considered important lessons to promote accurate perinatal mortality reporting: (i) a universal reporting system for Australia utilising a multidisciplinary team; (ii) a high perinatal autopsy rate, especially in the critical area of antepartum death with no identifiable cause; and (iii) standardised definitions for avoidability. Attention to these areas may prompt further research and changes in practice to further reduce perinatal mortality.
PROGRESS IN UREMIC TOXIN RESEARCH: Conservative Treatment of the Uremic Syndrome
Authors: Vanholder Raymond , Argilés Angel , Beige Joachim , Brunet Philippe , Drüeke Tilman B. , Fliser Danilo , Herget‐Rosenthal Stefan , Hörl Walter H. , Jörres Achim , Perna Alessandra , Rodriguez‐Portillo Mariano , Spasovski Goce , Stegmayr Bernd , Stenvinkel Peter , Wanner Christoph , Wiecek Andrzej , Massy Ziad A. 
Published: August 2009

AbstractIn addition to extracorporeal renal replacement strategies, which in chronic kidney disease (CKD) are largely reserved for the treatment of end‐stage kidney failure, conservative measures can be taken to reduce concentration, effects, or both concentration and effects of uremic retention solutes. In this overview, we will focus on those therapies, which are aimed at preventing or delaying cardio‐vascular disease, retarding or halting the progression of CKD, or both. We will discuss, consecutively, inhibitors of the renin–angiotensin–aldosterone axis, beta‐blockers, calcium‐channel antagonists, anti‐inflammatory drugs, intestinal sorbents, calcimimetics, and glitazones. Some of these approaches could lead to a therapeutic breakthrough in the future. In addition, comprehensive tables will be provided for more traditional therapeutic approaches, such as lifestyle changes and other pharmaceutical treatments.
Typology of High Users of Health Services Among a Rural Medicaid Population
Authors: Macnee Carol L. , McCabe Susan , Clarke Pamela N. , Fiske Marilyn , Campbell Sara 
Published: August 2009

ABSTRACT
Objectives: To identify a typology for high system users among a rural Medicaid population that could assist policy makers and providers in better and more efficiently serving this population.Design and Sample: Exploratory secondary data analysis of a large integrated Medicaid database in a western state. Five hundred and thirty‐nine Medicaid recipients receiving 2 or more state services and receiving 10 or more unique medications.Measures: Data analysis examining health care use, medication use, and demographic characteristics using SAS to identify patterns of use of services in the population. Results were confirmed with a statewide sample of 2,287 Medicaid users.Results: 3 characteristics—(1) use of 36 or more health care services in a year; (2) no gap in health care service use over the entire year; and (3) use of >12 health care services in 1 month—describe high‐risk groups of Medicaid users.Conclusions: Public health nurses, particularly as case managers and program planners, can look at service use patterns through client histories and their own agency records, in order to identify high‐risk groups who may benefit the most from programs that address their support, education, and coordination of health care needs.
Contextual Factors Influencing the Evolution of Nurses' Roles in a Primary Health Care Clinic
Authors: Paterson Barbara L. , Duffett‐Leger Linda , Cruttenden Kathleen 
Published: August 2009

ABSTRACT Objectives:The purpose of the research was to explore the everyday experiences and responses of stakeholders of a university‐sponsored nurse‐managed clinic (CHC) in regard to how nurses' roles in the clinic changed over time and the factors that influenced this change.Design and Sample:The research used a qualitative interpretive description design to interpret participants' accounts of their experience and perspectives as constructed narratives. The participants (N=23) included clients, community members who were volunteers at the CHC, staff of other community agencies or organizations, and nursing or social work students who had a clinical learning experience at the CHC.Measures:Data collection involved two interviews, one semistructured, face‐to‐face interview at the location selected by the participant, and a group interview held in a boardroom at the CHC. Each interview lasted approximately 60–90 min.Results:The research findings revealed the profound effects of the social, political, and economic context in determining nurses' roles within a nurse‐managed primary health care clinic. The evolution of nursing roles occurred in reaction to these effects, causing the nurses within the CHC to juggle their priorities and commitments.Conclusions:The study provides a contemporary example of the political activism work of nurses that is often invisible and illustrates how the commitment of primary health care nurses to social justice contributes in a significant way to the resolution of health inequities experienced by marginalized populations.
Pediatric convulsive status epilepticus in Honduras, Central America
Authors: Molinero Marco R. , Holden Kenton R. , Rodriguez Luis C. , Collins Julianne S. , Samra Jose A. , Shinnar Shlomo 
Published: August 2009

SummaryConvulsive status epilepticus (SE) in children is an important public health problem, particularly in low‐resource countries. A surveillance study was performed with consecutive enrollment of all children presenting with convulsive SE to Hospital Escuela Materno‐Infantil Emergency Department in Tegucigalpa, Honduras over a 13‐week period in 2003. In the 47 children with SE, the mean age was 4.5 years and the median seizure duration was 95 min. Mortality and morbidity were higher in children from rural locations, with all six deaths and three cases of new neurologic abnormalities occurring in rural children who had acute symptomatic SE. We conclude that childhood SE is common in the low‐resource developing country of Honduras. Given the long delays in obtaining initial treatment in pediatric emergency facilities, availability of prehospital treatment may be of particular importance in this setting.
HLA Class I markers in Japanese patients with carbamazepine‐induced cutaneous adverse reactions
Authors: Ikeda Hiroko , Takahashi Yukitoshi , Yamazaki Etsuko , Fujiwara Tateki , Kaniwa Nahoko , Saito Yoshiro , Aihara Michiko , Kashiwagi Mariko , Muramatsu Masaaki 
Published: August 2009

SummaryCarbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse drug reactions (cADRs) that may range from mild to severe. It is reported recently that the human leukocyte antigen HLA‐B*1502 is associated with Stevens‐Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I in 15 Japanese patients who fulfilled the diagnostic criteria for CBZ‐induced cADRs (mild in 10 and severe = SJS in 5). HLA‐B*1518, HLA‐B*5901 and HLA‐C*0704 alleles showed higher relative risks (above 10.0) for severe cADRs. The haplotype (HLA‐A*2402‐B*5901‐C*0102) had high relative risk (16.09) for severe cADRs. In patients with severe cADRs, frequencies of HLA‐A*1101, HLA‐A*3303, HLA‐B*1501, HLA‐B*4403, HLA‐B*5101, HLA‐B*5201, HLA‐C*0702, and HLA‐C*1202 alleles are relatively lower than in the Japanese population. These data may suggest that HLA‐B*5901 is one of the candidate markers for CBZ‐induced SJS in Japanese.
Middle short gyrus of the insula implicated in speech production: Intracerebral electric stimulation of patients with epilepsy
Authors: Afif Afif , Minotti Lorella , Kahane Philippe , Hoffmann Dominique 
Published: August 2009

SummaryPurpose:  Different lines of evidence have suggested an involvement of the insular cortex in speech production. These have included results from lesion studies, functional imaging techniques, and electrical stimulation of the human insular cortex during invasive evaluation of epileptic patients.Methods:  We evaluated 25 patients who had drug refractory focal epilepsy with at least one electrode stereotactically implanted in the insular cortex.Results:  Eight responses to insular cortex electrical stimulation were reported by five patients as speech arrest (five responses) and a lowering of voice intensity (three responses).Conclusions:  Data from this study implicate the middle short gyrus of the insula in the production of speech and show the importance of intrainsular electrode implantation during invasive pre‐resection evaluation by stereo‐electroencephalography (SEEG) when speech arrest occurs early in seizure semiology.
In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy
Authors: Yakushev Igor Y. , Dupont Erwan , Buchholz Hans‐Georg , Tillmanns Julia , Debus Fabian , Cumming Paul , Heimann Axel , Fellgiebel Andreas , Luhmann Heiko J. , Landvogt Christian , Werhahn Konrad J. , Schreckenberger Mathias , Potschka Heidrun , Bartenstein Peter 
Published: August 2009

SummaryPurpose: Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.Methods: Six pilocarpine‐treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [18F]‐fallypride, a high‐affinity dopamine D2/3receptor ligand. Parametric images of [18F]‐fallypride specific binding were calculated using a reference tissue method, and the two groups were contrasted by whole‐brain voxel‐based analysis implemented in statistical parametric mapping (SPM5).Results: Dopamine D2/3receptor availability was 27% lower in the bilateral anterior caudate‐putamen of pilocarpine‐treated rats as compared to controls (p < 0.05), but binding was unaffected in other striatal or extrastriatal regions.Conclusions: The finding of substantially reduced availability of dopamine D2/3receptors in the anterior caudate‐putamen of rats during the chronic phase of the pilocarpine model is in agreement with results of invasive (microinjection, microdialysis) animal studies that have revealed increased dopamine tonus and a D2/3receptor–mediated anticonvulsant action of dopamine in the anterior segment of the rat striatum. The present PET approach could be prospectively applied for monitoring dopamine receptor changes longitudinally, that is, at different phases of the epileptogenic process, and opens perspectives for testing dopaminergic agents as potential antiepileptogenic drugs.
Antiepileptic drugs abolish ictal but not interictal epileptiform discharges in vitro
Authors: D’Antuono Margherita , Köhling Rüdiger , Ricalzone Serena , Gotman Jean , Biagini Giuseppe , Avoli Massimo 
Published: August 2009

SummaryPurpose:  We established the effects of the antiepileptic drugs (AEDs) carbamazepine (CBZ), topiramate (TPM), and valproic acid (VPA) on the epileptiform activity induced by 4‐aminopyridine (4AP) in the rat entorhinal cortex (EC) in an in vitro brain slice preparation.Methods:  Brain slices were obtained from Sprague‐Dawley rats (200–250 g). Field and intracellular recordings were made from the EC during bath application of 4AP (50 μm). AEDs, and in some experiments, picrotoxin were bath applied concomitantly.Results:  Prolonged (>3 s), ictal‐like epileptiform events were abolished by CBZ (50 μm), TPM (50 μm), and VPA (1 mm), whereas shorter (<3 s) interictal‐like discharges continued to occur, even at concentrations up to 4‐fold as high. γ‐Aminobutyric acid (GABA)A–receptor antagonism changed the 4AP‐induced activity into recurrent interictal‐like events that were not affected by CBZ or TPM, even at the highest concentrations. To establish whether these findings reflected the temporal features of the epileptiform discharges, we tested CBZ and TPM on 4AP‐induced epileptiform activity driven by stimuli delivered at 100‐, 10‐, and 5‐s intervals; these AEDs reduced ictal‐like responses to stimuli at 100‐s intervals at nearly therapeutic concentrations, but did not influence shorter interictal‐like events elicited by stimuli delivered every 10 or 5 s.Conclusions:  We conclude that the AED ability to control epileptiform synchronization in vitro depends mainly on activity‐dependent characteristics such as discharge duration. Our data are in keeping with clinical evidence indicating that interictal activity is unaffected by AED levels that are effective to stop seizures.