bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective analysis of the impact of VEGF‐A gene polymorphisms on the pharmacodynamics of bevacizumab‐based therapy in metastatic breast cancer patients
Authors: Etienne‐Grimaldi Marie‐Christine , Formento Patricia , Degeorges Armelle , Pierga Jean‐Yves , Delva Rémi , Pivot Xavier , Dalenc Florence , Espié Marc , Veyret Corinne , Formento Jean‐Louis , Francoual Mireille , Piutti Magali , de Crémoux Patricia , Milano Gérard 
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Functional polymorphisms on the VEGF‐A gene, known to be linked to cancer risk or to VEGF‐A plasma concentrations, have been identified. So far, limited knowledge has been published on the relationships between toxicity/efficacy of bevacizumab‐based therapy and VEGF‐A polymorphisms (tumoral DNA). We therefore prospectively tested the impact of these five gene polymorphisms (blood DNA) on the pharmacodynamics of bevacizumab‐based treatment administered in metastatic breast cancer patients. WHAT THIS STUDY ADDS • Present data obtained from a prospective study suggest a role for VEGF‐A 936C > T polymorphism as a potential predictor of time to progression in breast cancer patients receiving bevacizumab‐containing therapy. Also, the VEGF‐A−634G > C polymorphism was linked to bevacizumab‐related toxicity.AIMS To test prospectively the impact of VEGF‐A gene polymorphisms on the pharmacodynamics of bevacizumab‐chemotherapy in breast cancer patients.METHODS As part of the single‐arm MO19391 trial, 137 women with locally recurrent or metastatic breast cancer receiving first‐line bevacizumab‐containing therapy were analysed. Patients received bevacizumab associated (76%) or not (24%) with taxane‐based chemotherapy. Clinical evaluation included clinical response, time to progression (TTP) and a toxicity score corresponding to the sum of each maximum observed toxicity grade (hypertension, haemorrhage, arterial and venous thrombo‐embolism). Functional VEGF‐A polymorphisms at position −2578 C > A, −1498 T > C, −1154 G > A, −634 G > C and 936 C > T were analysed by PCR‐RFLP (blood DNA).RESULTS Overall response rate (complete response (CR) + partial response (PR)) was 61%. Median TTP was 11 months. None of the VEGF‐A polymorphisms was significantly linked to clinical response. Analysis of the 936C > T polymorphism revealed that the 96 patients homozygous for the 936C allele exhibited a marked tendency for a shorter TTP (median 9.7 months) than the 32 patients bearing the 936T allele (median 11.5 months, P= 0.022) of which 30 were CT and two were homozygous TT. Other polymorphisms did not influence TTP. VEGF‐A−634 G > C was significantly related to the toxicity score with 39%, 49% and 81% of patients with score >1 in GG, GC and CC patients, respectively (P= 0.01).CONCLUSIONS The role for VEGF‐A 936C > T polymorphism as a potential marker of TTP in breast cancer patients receiving bevacizumab‐containing therapy concords with the known impact of VEGF‐A 936C > T polymorphism on VEGF‐A expression.
Cannabis‐related hospitalizations: unexpected serious events identified through hospital databases
Authors: Jouanjus Emilie , Leymarie Florence , Tubery Marie , Lapeyre‐Mestre Maryse 
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The general knowledge on cannabis toxicity has improved, but quantitative data are still lacking.• Little is known about the somatic complications associated with cannabis exposure. Available data rest upon case reports and only a few studies have been conducted in this field.• Psychiatric disorders related to cannabis exposure are somehow still controversial.WHAT THIS STUDY ADDS• Quantitative estimates are key to comprehending the risks of medical outcomes in cannabis users, in particular the somatic complications of use. Our study suggests that cannabis use has to be linked to serious health defects, particularly neurological and cardiovascular disorders.• Our study gives estimates of the annual incidence of cannabis‐related hospitalizations.• Our study should contribute to enhancing the medical management of cannabis using patients.AIMS Cannabis is the most prevalent illicit drug used worldwide and can be responsible for serious health defects in users. However, the risk related to cannabis consumption is not well established. The present study aimed to assess cannabis‐related adverse events leading to hospitalization, and to estimate the corresponding annual risk for consumers.METHODS Participants were patients admitted to the public hospitals in the Toulouse area (France) between January 2004 and December 2007 in relation to the use of cannabis. Reasons for admission and other occurring events were identified through hospital discharge summaries. We described all observed adverse events (AEs) and estimated their regional incidence on the basis of cannabis consumption data.RESULTS We included 200 patients, and identified a total of 619 adverse events (AEs), one of which was lethal. Psychiatric disorders involved 57.7% of patients and accounted for 18.2% of AEs. Most frequent outcomes were central and peripheral nervous system disorders (15.8% of AEs), acute intoxication (12.1%), respiratory system disorders (11.1%) and cardiovascular disorders (9.5%). We estimated that in 2007 the incidence of cannabis‐related AEs in the Midi‐Pyrenees region ranged from 1.2 per 1000 regular cannabis users (95% confidence interval (CI) 0.7, 1.6) to 3.2 (95% CI 2.5, 3.9).CONCLUSIONS Cannabis use is associated with complications, considered to be serious since they lead to hospitalization. Beyond the well‐known and widely investigated psychiatric events, serious cerebro and cardiovascular complications have been identified. These findings contribute to improve the knowledge of cannabis‐related adverse events.
Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren
Authors: Tapaninen Tuija , Neuvonen Pertti J. , Niemi Mikko 
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Aliskiren is an antihypertensive drug with a low oral bioavailability.• Aliskiren is eliminated primarily unchanged into bile, and it is a substrate of the organic anion transporting polypeptide 2B1 (OATP2B1) influx transporter, the P‐glycoprotein efflux transporter and cytochrome P450 3A4.• Flavonoids in orange and apple juice have been shown to inhibit OATP2B1in vitro.WHAT THIS STUDY ADDS• Orange juice and apple juice markedly reduce the plasma concentrations of aliskiren probably by inhibiting its OATP2B1‐mediated intestinal absorption.• Concomitant intake of aliskiren with orange or apple juice is best avoided.AIMThe aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren.METHODSIn a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150‐mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h.RESULTSOrange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%,P< 0.001) and 84% (95% CI 72%, 91%,P< 0.001), and the area under the plasma aliskiren concentration–time curve (AUC) by 62% (95% CI 47%, 72%,P< 0.001) and 63% (95% CI 46%, 74%,P< 0.001), respectively, but had no significant effect on its elimination half‐life or renal clearance. The decreases in aliskiren AUC by orange and apple juice correlated with aliskiren AUC during the water phase (r= 0.98,P< 0.001). Plasma renin activity was 87% and 67% higher at 24 h after aliskiren during the orange juice and apple juice phases, respectively, than during the water phase (P< 0.05).CONCLUSIONSOrange juice and apple juice greatly reduce the plasma concentrations and renin‐inhibiting effect of aliskiren, probably by inhibiting its OATP2B1‐mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided.
Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man
Authors: Coiro Vittorio , Volpi Riccardo , Casti Amos , Maffei Maria Ludovica , Stella Adriano , Volta Elio , Chiodera Paolo 
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Alprazolam (ALP), a benzodiazepine activating GABAergic receptors, is involved in ACTH secretion. WHAT THIS STUDY ADDS • This study demonstrates a partial opioid influence in the inhibitory effect of ALP on the release of ACTH/cortisol during physical exercise.AIMS To establish the possible involvement of alprazolam (ALP) and/or opiates in the mechanism underlying the ACTH/cortisol response to physical exercise.METHODS Tests were carried out under basal conditions (exercise control test), exercise plus ALP (50 µg at time −90 min), naloxone (10 mg at time 0) or ALP plus naloxone. Plasma ACTH and serum cortisol concentrations were evaluated in blood samples taken before, during and after the bicycle ergometer tests.RESULTS ACTH and cortisol concentrations rose significantly after physical exercise. Maximum peak at time 15 min (P ≤ 0.01 vs. baseline) for ACTH and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol. In the presence of naloxone, the ACTH and cortisol responses were significantly increased (maximum peak at time 20 min, P ≤ 0.02 vs. control test for ACTH, and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol) whereas they were abolished by ALP. When ALP and naloxone were given together, the inhibitory effect of ALP was partial.CONCLUSIONS These data demonstrate an inhibitory effect of ALP in the regulation of the ACTH/cortisol response to physical exercise in man and suggest that GABAergic receptor activating benzodiazepines and opioids interact in the neuroendocrine secretion of ACTH/cortisol.
The role of starlings in the spread of Salmonella within concentrated animal feeding operations
Authors: Carlson James C. , Franklin Alan B. , Hyatt Doreene R. , Pettit Susan E. , Linz George M. 
Published: December 2010

Summary 1. Characterizing and mitigating the disease risks associated with wildlife use of concentrated animal feeding operations (CAFOs) can reduce the spread of micro‐organisms throughout the environment while increasing agricultural productivity. To better understand the disease risks associated with bird use of CAFOs, we assessed the capacity of European starlings Sturnus vulgaris to spread Salmonella enterica to cattle, their feed and water. 2. We sampled starlings, cattle feed, cattle water and cattle faeces from 10 CAFOs in Texas, USA. Samples were screened for Salmonella enterica to investigate: (i) the prevalence of S. enterica in starlings using CAFOs, (ii) whether there was a relationship between cattle infections and starling numbers, and (iii) if S. enterica contamination of cattle feed and water was related to numbers of starlings observed on CAFOs. 3. We used generalized linear mixed logistic regression models to assess the importance of starlings, cattle stocking, facility management and environmental variables in the transmission of S. enterica to cattle, feed troughs and water troughs in CAFOs. 4. Starling gastrointestinal tract samples tested positive for S. enterica (2·5% prevalence; 95% CI = 0·3%, 8·6%) and starlings were retained as model covariates in the best supported logistic regression models for S. enterica contamination within cattle feed, water and faeces. 5. Salmonella enterica contamination of both cattle feed troughs and water troughs is significantly related to numbers of starlings. Contamination in cattle feed increased as more starlings entered feed troughs. Contamination in water troughs increased asymptotically as numbers of starlings on CAFOs increased. Starling variables in the cattle faecal shedding model were not significant. 6. Synthesis and applications. The numbers of European starlings better explained S. enterica contamination of cattle feed and water than other variables including cattle stocking, facility management and environmental variables. This suggests that starlings are a source of S. enterica contamination in CAFOs. Thus, starling management tools such as population control, habitat management, exclusionary devises and bird repellents may be used to reduce the amplification and spread of disease within livestock production systems.
Virulence in Trypanosoma congolense Savannah subgroup. A comparison between strains and transmission cycles
Authors: VAN den BOSSCHE P. , CHITANGA S. , MASUMU J. , MARCOTTY T. , DELESPAUX V. 
Published: December 2010

SummaryTrypanosoma congolense strains have been shown to differ in their virulence both between subgroups and within the Savannah subgroup between strains. This review revisits these findings and complements them with information on the virulence of T. congolense Savannah subgroup strains isolated from cattle (domestic transmission cycle) in different geographical areas and of strains isolated in protected areas where trypanotolerant wildlife species are the reservoir of the trypanosomes (sylvatic transmission cycle). The virulence of a total of 62 T. congolense Savannah subgroup strains (50 domestic and 12 sylvatic), determined using a standard protocol in mice, was compared. Virulence varied substantially between strains with, depending on the strain, the median survival time of infected mice varying from five to more than sixty days. The proportion of highly virulent strains (median survival time <10 days) was significantly (P = 0·005) higher in strains from the sylvatic transmission cycle. The analysis highlights repercussions of the domestication of the trypanosomiasis transmission cycle that may have to be taken in consideration in the development of trypanosomiasis control strategies.
AtNUFIP, an essential protein for plant development, reveals the impact of snoRNA gene organisation on the assembly of snoRNPs and rRNA methylation in Arabidopsis thaliana
Authors: Rodor Julie , Jobet Edouard , Bizarro Jonathan , Vignols Florence , Carles Cristel , Suzuki Takamasa , Nakamura Kenzo , Echeverría Manuel 
Published: December 2010

SummaryIn all eukaryotes, C/D small nucleolar ribonucleoproteins (C/D snoRNPs) are essential for methylation and processing of ribosomal RNAs. They consist of a box C/D small nucleolar RNA (C/D snoRNA) associated with four highly conserved nucleolar proteins. Recent data in HeLa cells and yeast have revealed that assembly of these snoRNPs is directed by NUFIP protein and other auxiliary factors. Nevertheless, the precise function and biological importance of NUFIP and the other assembly factors remains unknown. In plants, few studies have focused on RNA methylation and snoRNP biogenesis. Here, we identify and characterise the AtNUFIP gene that directs assembly of C/D snoRNP. To elucidate the function of AtNUFIP in planta, we characterized atnufip mutants. These mutants are viable but have severe developmental phenotypes. Northern blot analysis of snoRNA accumulation in atnufip mutants revealed a specific degradation of C/D snoRNAs and this situation is correlated with a reduction in rRNA methylation. Remarkably, the impact of AtNUFIP depends on the structure of snoRNA genes: it is essential for the accumulation of those C/D snoRNAs encoded by polycistronic genes, but not by monocistronic or tsnoRNA genes. We propose that AtNUFIP controls the kinetics of C/D snoRNP assembly on nascent precursors to overcome snoRNA degradation of aberrant RNPs. Finally, we show that AtNUFIP has broader RNP targets, controlling the accumulation of scaRNAs that direct methylation of spliceosomal snRNA in Cajal bodies.
Multiple cytosolic and transmembrane determinants are required for the trafficking of SCAMP1 via an ER–Golgi–TGN–PM pathway
Authors: Cai Yi , Jia Tianran , Lam Sheung Kwan , Ding Yu , Gao Caiji , San Melody Wan Yan , Pimpl Peter , Jiang Liwen 
Published: December 2010

SummaryHow polytopic plasma membrane (PM) proteins reach their destination in plant cells remains elusive. Using transgenic tobacco BY‐2 cells, we previously showed that the rice secretory carrier membrane protein 1 (SCAMP1), an integral membrane protein with four transmembrane domains (TMDs), is localized to the PM and trans‐Golgi network (TGN). Here, we study the transport pathway and sorting signals of SCAMP1 by following its transient expression in tobacco BY‐2 protoplasts and show that SCAMP1 reaches the PM via an endoplasmic reticulum (ER)–Golgi–TGN–PM pathway. Loss‐of‐function and gain‐of‐function analysis of various green fluorescent protein (GFP) fusions with SCAMP1 mutations further demonstrates that: (i) the cytosolic N‐terminus of SCAMP1 contains an ER export signal; (ii) the transmembrane domain 2 (TMD2) and TMD3 of SCAMP1 are essential for Golgi export; (iii) SCAMP1 TMD1 is essential for TGN‐to‐PM targeting; (iv) the predicted topology of SCAMP1 and its various mutants remain identical as demonstrated by protease protection assay. Therefore, both the cytosolic N‐terminus and TMD sequences of SCAMP1 play integral roles in mediating its transport to the PM via an ER–Golgi–TGN pathway.
A small molecule with differential effects on the PTS1 and PTS2 peroxisome matrix import pathways
Authors: Brown Laura‐Anne , O’Leary‐Steele Catherine , Brookes Paul , Armitage Lynne , Kepinski Stefan , Warriner Stuart L. , Baker Alison 
Published: December 2010

SummaryThe use of small molecules has great power to dissect biological processes. This study presents the identification and characterisation of an inhibitor of peroxisome matrix protein import. A mini‐screen was carried out to identify molecules that cause alteration in peroxisome morphology, or mislocalization of a peroxisome targeted fluorescent reporter protein. A benzimidazole lead compound (LDS‐003655) was identified that resulted in reduced GFP fluorescence in peroxisomes and cytosolic GFP accumulation. The effect of the compound was specific to peroxisomes as Golgi bodies, endoplasmic reticulum and the actin cytoskeleton were unaffected even at 25 μm, whereas peroxisome import via the PTS1 pathway was compromised at 100 nm. When seedlings were grown on 25 μm LDS‐003655 they displayed morphology typical of seedlings grown in the presence of auxin, and expression of the auxin reporter DR5::GFP was induced. Analysis of a focussed library of LDS‐003655 derivatives in comparison with known auxins led to the conclusion that the auxin‐like activity of LDS‐003655 is attributable to its in situ hydrolysis giving rise to 2,5‐dichlorobenzoic acid, whereas the import inhibiting activity of LDS‐003655 requires the whole molecule. None of the auxins tested had any effect on peroxisome protein import. Matrix import by the PTS2 import pathway was relatively insensitive to LDS‐003655 and its active analogues, with effects only seen after prolonged incubation on high concentrations. Steady‐state protein levels of PEX5, the PTS1 import pathway receptor, were reduced in the presence of 100 nm LDS‐003655, suggesting a possible mechanism for the import inhibition.
A practical, algorithmic approach to diagnosing hair shaft disorders
Authors: Mirmirani Paradi , Huang Kathie P. , Price Vera H. 
Published: December 2010

AbstractThe hair shaft is a unique structure composed of an inner cortex and a protective outer cuticle. Any defects in this normal structure due to genetics or the environment can lead to variations in physical properties. Thus one should suspect a hair shaft disorder if a patient presents with an abnormality or change in hair texture, appearance, manageability or ability to grow hair long. A key feature of the clinical evaluation is to determine whether there is hair breakage (increased fragility) by looking for broken hairs and performing a tug test. Once this determination is made, an algorithmic approach can be used to narrow the differential diagnosis: hair shaft disorders with and without fragility. A hair mount along with other directed questions and examination will almost always allow the clinician to make an in‐office diagnosis. Common case scenarios, photographs, and practical tips are provided to illustrate the use of this algorithmic approach in the diagnosis of hair shaft disorders. We have also included a summary of the molecular defects where known, which can be helpful in providing a correlation with clinical findings, in counseling patients, and potentially offering treatment options.
Visuospatial impairment in children and adolescents after liver transplantation
Authors: Haavisto Anu , Korkman Marit , Törmänen Jussi , Holmberg Christer , Jalanko Hannu , Qvist Erik 
Published: December 2010

Haavisto A, Korkman M, Törmänen J, Holmberg C, Jalanko H, Qvist E. Visuospatial impairment in children and adolescents after liver transplantation. Pediatr Transplantation 2011: 15:184–192. © 2010 John Wiley & Sons A/S.Abstract:  A minority of children with liver transplants exhibit significant delay in global intelligence; others have specific learning disabilities. More specific data on neurocognitive strengths and weaknesses are lacking. Eighteen children aged 7–16 yr, who had undergone LTx in Finland participated in the study. They were assessed on an average 7.6 (s.d. 4.5, range 1.0–15.0) years post‐operatively at a mean age of 11.8 (s.d. 3.1, range 7.2–16.1). A standardized test of intelligence (WISC‐III), a neuropsychological test battery (NEPSY‐II), and a parental questionnaire on the child’s development (FTF) were administered. The neuropsychological test profile of the LTx group was compared with that of a matched control group of healthy children. The LTx children achieved on an average normal FSIQ 94.0 and VIQ 99.6. Their Performance Intelligence Quotient (PIQ 88.9, p = 0.043) was, however, significantly lower than the population mean. On neuropsychological assessment, the LTx children scored generally lower than the control group (p = 0.004), a difference significant in sub‐tests assessing visuospatial and visuoconstructive functions and social perception. No differences emerged in sub‐tests of attention and executive functions, memory and learning, or language functions. LTx children are at increased risk for impairment in the visuospatial domain.
The Western Pacific Regional Child Survival Strategy: Progress and challenges in implementation
Authors: Jayawardena Nelu , Subhi Rami , Duke Trevor 
Published: December 2010

AbstractThe Regional Child Survival Strategy (RCSS) was launched by the World Health Organization and United Nations Children's Fund in 2006. This initially involved the six highest mortality burden countries in the region (Cambodia, China, Laos PDR, Papua New Guinea, Philippines and Vietnam). This paper aimed to describe the experiences of countries in the region in adopting and implementing the RCSS, and to identify factors that promote and impede progress. Child mortality has fallen substantially since 1990, and the region as a whole is on track to achieve the Millennium Development Goal 4 (MDG‐4) targets. Some countries have made slower progress and are struggling. There is an urgent need to support countries that have, until now, not been included in the RCSS, particularly smaller Pacific Island nations, and to provide greater support to the poorest countries if MDG‐4 targets for the region are to be achieved.