bluuebunny/crossref_metadata_2025 huggingface dataset:
Response inhibition and reward anticipation in medication‐naïve adults with attention‐deficit/hyperactivity disorder: A within‐subject case‐control neuroimaging study
Authors: Carmona Susana , Hoekzema Elseline , Ramos‐Quiroga J. Antoni , Richarte Vanesa , Canals Clara , Bosch Rosa , Rovira Mariana , Carlos Soliva Juan , Bulbena Antonio , Tobeña Adolf , Casas Miguel , Vilarroya Oscar
Published: August 2011

Background: Previous research suggests that ADHD patients are characterized by both reduced activity in the inferior frontal gyrus (IFG) during response inhibition tasks (such as the Go‐NoGo task), and reduced activity in the ventral striatum during reward anticipation tasks (such as the Monetary‐Incentive‐Delay [MID] task). However, no prior research has applied either of these paradigms in medication‐naïve adults with ADHD, nor have these been implemented in an intrasubject manner. Methods: The sample consisted of 19 medication‐naïve adults with ADHD and 19 control subjects. Main group analyses were based on individually defined regions of interest: the IFG and the VStr for the Go‐NoGo and the MID task respectively. In addition, we analyzed the correlation between the two measures, as well as between these measures and the clinical symptoms of ADHD. Results: We observed reduced bilateral VStr activity in adults with ADHD during reward anticipation. No differences were detected in IFG activation on the Go‐NoGo paradigm. Correlation analyses suggest that the two tasks are independent at a neural level, but are related behaviorally in terms of the variability of the performance reaction time. Activity in the bilateral VStr but not in the IFG was associated negatively with symptoms of hyperactivity/impulsivity. Conclusions: Results underline the implication of the reward system in ADHD adult pathophysiology and suggest that frontal abnormalities during response inhibition performance may not be such a pivotal aspect of the phenotype in adulthood. In addition, our findings point toward response variability as a core feature of the disorder. Hum Brain Mapp 33:2350–2361, 2012. © 2011 Wiley Periodicals, Inc.
Ultrasound‐guided fine needle aspiration diagnosis of supraglottic laryngeal cancer
Authors: Lopchinsky Richard A. , Amog‐Jones Glenda F. , Pathi Renuka
Published: August 2011

Background.Although intraoperative laryngoscopic examination and biopsy of patients who present with locally advanced supraglottic carcinomas remains the standard of care, there are occasions when a more expedited biopsy can be helpful.

Methods and Results.We describe a quick diagnostic technique of ultrasound‐guided fine needle aspiration of endolaryngeal advanced supraglottic carcinomas, which can be performed in the clinic without any preparation. Ultrasound scanning is performed through the thyrohyoid membrane. The tumor is visualized as an irregular hypoechoic mass. While continuing to visualize the mass, a 21‐gange needle attached to a syringe is passed through the contralateral thyrohyoid membrane into the mass. Suction is applied, and the aspirate is sent for cytologic study.

Conclusions.When formal intraoperative laryngoscopy and biopsy is not feasible or timely, ultrasound‐guided fine‐needle aspiration biopsy enables a rapid diagnosis and eliminates the cost, side effects, and risks of a direct laryngoscopy. © 2011 Wiley Periodicals, Inc.† Head Neck, 2013
Protease profiling of liver fibrosis reveals the ADAM metallopeptidase with thrombospondin type 1 motif, 1 as a central activator of transforming growth factor beta
Authors: Bourd-Boittin Katia , Bonnier Dominique , Leyme Anthony , Mari Bernard , Tuffery Pierre , Samson Michel , Ezan Frédéric , Baffet Georges , Theret Nathalie
Published: August 2011

During chronic liver disease, tissue remodeling leads to dramatic changes and accumulation of matrix components. Matrix metalloproteases and their inhibitors have been involved in the regulation of matrix degradation. However, the role of other proteases remains incompletely defined. We undertook a gene-expression screen of human liver fibrosis samples using a dedicated gene array selected for relevance to protease activities, identifying the ADAMTS1 (A Disintegrin And Metalloproteinase [ADAM] with thrombospondin type 1 motif, 1) gene as an important node of the protease network. Up-regulation of ADAMTS1 in fibrosis was found to be associated with hepatic stellate cell (HSC) activation. ADAMTS1 is synthesized as 110-kDa latent forms and is processed by HSCs to accumulate as 87-kDa mature forms in fibrotic tissues. Structural evidence has suggested that the thrombospondin motif-containing domain from ADAMTS1 may be involved in interactions with, and activation of, the major fibrogenic cytokine, transforming growth factor beta (TGF-β). Indeed, we observed direct interactions between ADAMTS1 and latency-associated peptide-TGF-β (LAP-TGF-β). ADAMTS1 induces TGF-β activation through the interaction of the ADAMTS1 KTFR peptide with the LAP-TGF-β LKSL peptide. Down-regulation of ADAMTS1 in HSCs decreases the release of TGF-β competent for transcriptional activation, and KTFR competitor peptides directed against ADAMTS1 block the HSC-mediated release of active TGF-β. Using a mouse liver fibrosis model, we show that carbon tetrachloride treatment induces ADAMTS1 expression in parallel to that of type I collagen. Importantly, concurrent injection of the KTFR peptide prevents liver damage.

Conclusion:

Our results indicate that up-regulation of ADAMTS1 in HSCs constitutes a new mechanism for control of TGF-β activation in chronic liver disease. (Hepatology 2011)
Genetic interactions in the adrenergic system genes: analysis of antipsychotic‐induced weight gain
Authors: Luca Vincenzo De , Souza Renan P. , Viggiano Emanuela , Sickert Laertes , Teo Celine , Zai Clement , Tiwari Arun K. , Müller Daniel J , Lieberman Jeffery A. , Volavka Jan , Meltzer Herbert Y. , Kennedy James L.
Published: August 2011

Atypical antipsychotics (AP) have high affinity for many neurotransmitter receptors. Among these receptors, APs are antagonist at α‐adrenergic and β‐adrenergic receptors, and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects.

Objective

We tested the hypotheses that AP‐induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes. We analyzed nine genetic polymorphisms across seven adrenergic genes (ADRA1A, ADRA2A, ADRA2C, ADRB3, DBH, MAOA and COMT).

Methods

One hundred thirty‐nine patients with schizophrenia were prospectively assessed for AP‐induced weight gain. The HelixTree software (Golden Helix, Bozeman, MT, USA) was employed to detect differences in genotypic distribution between weight gainer and non‐weight gainer groups. Furthermore, for the dopamine β‐hydroxylase haplotype, we were able to obtain both the molecular and the statistical phases, analyzing the phenotype considering both phases.

Results

Weight gain was not associated with any adrenergic gene.

Conclusions

Our results suggest that genetic polymorphisms in the adrenergic system may not play a major role in AP‐induced weight gain; however, adrenergic 2A receptor gene that produced previously the most consistent associations with this phenotype showed a significant interaction with the monoamine oxidase A in weight gainers. Copyright © 2011 John Wiley & Sons, Ltd.
The prevalence and clinical‐demographic correlates of diabetes mellitus in chronic schizophrenic patients receiving clozapine
Authors: Zhang Ruiling , Hao Wei , Pan Miao , Wang Chuansheng , Zhang Xiuli , Chen Da Chun , Xiu Mei Hong , De Yang Fu , Kosten Thomas R. , Zhang Xiang Yang
Published: August 2011

Objective

To examine the prevalence and correlates of diabetes in a large sample of Chinese patients with schizophrenia on long‐term clozapine treatment, because this population previously has received little systematic study.

Methods

Two hundred and six inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition schizophrenia criteria were recruited in a cross‐sectional naturalistic study, and compared with 615 healthy control subjects matched for age, sex, education, and body mass index (BMI). The patient's psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Diagnoses of diabetes were established through review of medical records and fasting blood glucose testing, or an oral glucose tolerance test.

Results

Diabetes mellitus was more common in patients than in the normal controls (22.3% vs 6.2%) (odds ratio = 4.37, confidence interval (CI) 2.76–6.92, p < 0.001). The prevalence of diabetes increased with age across five age‐groups as compared with normal controls (X2 = 18.0, df = 4, p = 0.001). The PANSS total score and sub‐scores showed no differences between the diabetic and non‐diabetic groups. Logistic regression in the patients revealed significant associations between diabetes and a family history of diabetes (p < 0.001), age (p < 0.01), and BMI (p < 0.05).

Conclusion

Long‐term clozapine treatment was associated with an increased and clinically important risk of diabetes mellitus in Chinese chronic schizophrenic patients, which is consistent with previous reports in Western populations. Copyright © 2011 John Wiley & Sons, Ltd.
Detection of mitochondrial deoxyribonucleic acid alterations in urine from urothelial cell carcinoma patients
Authors: Dasgupta Santanu , Shao Chunbo , Keane Thomas E. , Duberow David P. , Mathies Richard A. , Fisher Paul B. , Kiemeney Lambertus A. , Sidransky David
Published: August 2011

Our study aims at understanding the timing and nature of mitochondrial deoxyribonucleic acid (mtDNA) alterations in urothelial cell carcinoma (UCC) and their detection in urine sediments. The entire 16.5 kb mitochondrial genome was sequenced in matched normal lymphocytes, tumor and urine sediments from 31 UCC patients and compared to different clinical stages and histological grades. The mtDNA content index was examined in all the specimens. Sixty‐five percent (20/31) of the patients harbored at least 1 somatic mtDNA mutation. A total of 25 somatic mtDNA mutations were detected, which were more frequent in the respiratory complex coding regions (Complex I, III, IV and V) of the mtDNA and significantly affected respiratory Complex III compared to the other complexes (p = 0.021–0.039). Compared to Stage Ta, mtDNA mutation was higher in Stage T1 and significantly higher in Stage T2 (p = 0.01) patients. MtDNA mutation was also significantly higher (p = 0.04) in Stage T2 compared to Stage T1 patients. Ninety percent (18/20) of the patients harboring mtDNA mutation in the tumor also had mutation in their urine sediments. Eighty percent (20/25) of the tumor‐associated mtDNA mutations was detectable in the urine sediments. Compared to the normal lymphocytes, the mtDNA content increased significantly in the tumor (p = 0.0013) and corresponding urine sediments (p = 0.0025) in 19/25 (76%) patients analyzed. Our results indicate that mtDNA alterations occur frequently in progressive stages of UCC patients and are readily detectable in the urine sediments. MtDNA mutations appear to provide a promising tool for developing early detection and monitoring strategies for UCC patients.
Host‐derived osteopontin maintains an acute inflammatory response to suppress early progression of extrinsic cancer cells
Authors: Hsieh Yu‐Hua , Margaret Juliana M. , Ho Kang‐Jey , Kuo Hui‐Chien , van der Heyde Henri , Elmets Craig , Chang Pi‐Ling
Published: August 2011

The matricellular protein osteopontin (OPN), expressed in various cancer types and elevated in the blood of cancer patients, is thought to have different functions when derived from host versus cancer cells. To assess the effect of host‐derived OPN on growth of cancers of epithelial origin, we established a line of cutaneous squamous cell carcinoma (SCC) cells, named ONSC, which lacks the OPN gene and develops SCC in syngeneic wild‐type (WT) and OPN‐null mice. At 8 and/or 10 week after subcutaneous injection of ONSC cells in mice, however, there was a lower tumor incidence in WT mice, suggesting that host‐derived OPN is associated with suppression of early growth of extrinsic cancer cells. Histological, immunohistochemical, biochemical and hematological analyses were performed on the tumor microenvironment and blood from tumor‐bearing mice during the first week after implantation. Host‐derived OPN suppression of extrinsic ONSC cell progression is likely mediated through elicitation of an early innate inflammatory response, through its function as a chemoattractant and/or by enhancing survival of inflammatory cells. Further, consistent with a previous report, the serum levels of host‐derived OPN, which are elevated during the early phase of tumor growth in mice implanted with ONSC, appear to reflect an anti‐tumor progression effect.
Raman spectroscopy: a potential tool for early objective diagnosis of neoplasia in the oesophagus
Authors: Almond L. Max , Hutchings Joanne , Shepherd Neil , Barr Hugh , Stone Nick , Kendall Catherine
Published: August 2011

There is a profound clinical need for a diagnostic tool that will enable clinicians to identify early neoplastic change in the oesophagus. Raman Spectroscopy (RS) has demonstrated the potential to provide non‐invasive, rapid, objective diagnosis of endoscopically invisible precancerous oesophageal dysplasia in vitro. RS analyses biological material to identify highly specific biochemical information that can be used to influence clinical care. Raman spectroscopic mapping could provide automated assessment of tissue biopsies to aid histopathological diagnosis in vitro. Furthermore, the recent development of fibre‐optic Raman probes has enabled endoscopic assessment of oesophageal mucosa in vivo. Accurate identification of dysplasia will enable targeted endoscopic resection of early lesions preventing the development of oesophageal cancer. This review summarises the development of Raman systems for use as laboratory based analytical adjuncts and endoscopic diagnostic tools in the distal oesophagus. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Shear stress regulates expression of death‐associated protein kinase in suppressing TNFα‐induced endothelial apoptosis
Authors: Rennier Keith , Ji Julie Y.
Published: August 2011

Death associated protein kinase (DAPK) is a positive regulator in tumor necrosis factor α (TNFα)‐induced apoptotic pathway, and DAPK expression is lost in cancer cells. In the vasculature, misdirected apoptosis in endothelial cells leads to pathological conditions such as inflammation and physiological shear stress is protective against apoptosis. Using bovine aortic endothelial cells, we found that DAPK expression increased, while the auto‐inhibitory phosphorylation of serine 308 decreased with shear stress at 12 dynes/cm2 for 6 h. Quantitative RT‐PCR revealed a corresponding increase in DAPK mRNA [P < 0.01]. We found that after 18‐h TNFα induction, shearing cells for another 6 h significantly reduced apoptosis based on TUNEL staining [P < 0.05], although cell necrosis was not affected. Under the same conditions, we observed significantly decreased overall DAPK, as well as phospho‐serine 308 DAPK [P < 0.05] compared to TNFα treatment alone. Caspase‐3 and ‐7 activities downstream of DAPK were also attenuated. Shearing cells alone resulted in enhanced apoptosis, likely due to increased DAPK activity. Our findings were further supported by DAPK siRNA, which yielded contrary results. We present conclusive evidence for the first time that shear stress of up to 6 h up‐regulates DAPK expression and activation. However, in the presence of apoptotic stimuli such as TNFα, shear stress caused decrease in DAPK activity. In fact, long‐term shear stress of 24 h significantly reduced overall DAPK expression. Our findings strongly support a novel role for DAPK in mediating effects of shear stress in suppressing cytokine‐activated apoptosis. J. Cell. Physiol. 227: 2398–2411, 2012. © 2011 Wiley Periodicals, Inc.
CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle‐stimulating hormone and transforming growth factor β1 upregulation of steroidogenesis
Authors: Fang Wei‐Ling , Lee Ming‐Ting , Wu Leang‐Shin , Chen Yun‐Ju , Mason Jian , Ke Ferng‐Chun , Hwang Jiuan‐Jiuan
Published: August 2011

In vitro and in vivo studies implicate that follicle‐stimulating hormone (FSH) and transforming growth factor β1 (TGFβ1) play crucial physiological roles in regulating ovarian granulosa cell function essential to fertility control in females. FSH induces cAMP and calcium signaling, thereby activating transcription factor CREB to upregulate steroidogenic gene expression, and TGFβ1 greatly enhances FSH‐stimulated steroidogenesis. A CREB coactivator CRTC2/TORC2 was identified to function as a cAMP and calcium‐sensitive coincidence sensor. This led us to explore the role of CRTC2 and its regulator calcineurin in FSH and TGFβ1‐stimulated steroidogenesis. Primary culture of granulosa cells from gonadotropin‐primed immature rats was used. Immunoblotting analysis shows that FSH rapidly and transiently induced dephosphorylation/activation of CRTC2, and FSH + TGFβ1 additionally induced late‐phase CRTC2 dephosphorylation. Immunofluorescence analysis further confirms FSH ± TGFβ1 promoted CRTC2 nuclear translocation. Using selective inhibitors, we demonstrate that FSH activated CRTC2 in a PKA‐ and calcineurin‐dependent manner, and TGFβ1 acting through its type I receptor (TGFβRI)‐modulated FSH action in a calcineurin‐mediated and PKA‐independent fashion. Next, we investigated the involvement of calcineurin and CRTC2 in FSH and TGFβ1‐stimulated steroidogenesis. Calcineurin and TGFβRI inhibitor dramatically reduced the FSH ± TGFβ1‐increased progesterone synthesis and protein levels of StAR, P450scc, and 3β‐HSD enzyme. Furthermore, chromatin‐immunoprecipitation and immunoprecipitation analyses demonstrate that FSH ± TGFβ1 differentially increased CRTC2, CREB, and CBP binding to these steroidogenic genes, and CREB nuclear association with CRTC2 and CBP. In all, this study reveals for the first time that CRTC2 and calcineurin are critical signaling mediators in FSH and TGFβ1‐stimulated steroidogenesis in ovarian granulosa cells. J. Cell. Physiol. 227: 2430–2440, 2012. © 2011 Wiley Periodicals, Inc.
Expression of a Musashi‐like gene in sexual and asexual development of the colonial chordate Botryllus schlosseri and phylogenetic analysis of the protein group
Authors: Gasparini Fabio , Shimeld Sebastian M. , Ruffoni Elena , Burighel Paolo , Manni Lucia
Published: August 2011

Tunicates are the unique chordates to possess species reproducing sexually and asexually. Among them, the colonial ascidian Botryllus schlosseri is a reference model for the study of similarities and differences in these two developmental pathways. We here illustrate the characterization and expression pattern during both pathways of a transcript for a gene orthologous to Dazap1. Dazap1 genes encode for RNA‐binding proteins and fall into the Musashi‐like (Msi‐like) group. Our phylogenetic analysis shows that these are related to other RNA‐binding proteins (Tardbp and several heterogeneous nuclear ribonucleoproteins types) that share the same modular domain structure of conserved tandem RNA Recognition Motifs (RRMs). We also classify the whole group as derived from a single ancient duplication of the RRM. Our results also show that Dazap1 is expressed with discrete spatiotemporal pattern during embryogenesis and blastogenesis of B. schlosseri. It is never expressed in wholly differentiated tissues, but it is located in all bud tissues and in different spatiotemporally defined territories of embryos and larva. These expression patterns could indicate different roles in the two processes, but an intriguing relationship appears if aspects of cell division dynamics are taken into account, suggesting that it is related to the proliferative phases in all tissues, and raising a similarity with known Dazap1 orthologs in other metazoans. Dev. Evol.) 316:562–573, 2011. © 2011 Wiley Periodicals, Inc.
Variations of frequency of landfalling typhoons in East China, 1450–1949
Authors: Chan Johnny C. L. , Liu Kin‐Sik , Xu Ming , Yang Qiuzhen
Published: August 2011

On the basis of Chinese government records, the number of tropical cyclones making landfall along the East China coast during the period 1450–1949 is examined. The annual number of typhoons making landfall in East China during this period is found to possess a positive and statistically significant trend, as well as oscillations on centennial to decadal timescales. By classifying the years using proxy records of the El Niño and Pacific Decadal Oscillation phenomena, the annual number of typhoon landfall is found to vary with the different phases of these two prominent oscillations, and such variations can be explained to a large extent physically based on modern‐day atmospheric data. These results, together with those from previous studies, suggest that variations in the number of landfalling tropical cyclones are largely governed by those in the planetary‐scale atmospheric circulations that go through oscillations on various timescales. Copyright © 2011 Royal Meteorological Society
A coastal reservoir of terrestrial resources for neanderthal populations in north‐eastern Iberia: palaeoenvironmental data inferred from the small‐vertebrate assemblage of Cova del Gegant, Sitges, Barcelona
Authors: López‐García Juan Manuel , Blain Hugues‐Alexandre , Sanz Montserrat , Daura Joan
Published: August 2011

Coastal areas as reservoirs of resources for hominid groups have been widely studied in recent years. These areas combine marine with terrestrial and wetland resources and would have been optimum sites for hominids, including Neanderthals. This is the case with the Cova del Gegant, a cave that today opens directly onto the Mediterranean Sea and is located in the north‐eastern Iberian Peninsula. The geomorphological evolution of the Massis del Garraf has provided evidence that during the late Pleistocene there was a littoral platform between 8 and 13 km wide in front of the Cova del Gegant. Within this framework, the data derived from analysis of the small vertebrates and large mammals recovered from Cova del Gegant, including taxa currently absent from the Massis del Garraf, suggest that the landscape surrounding the cave provided a richer terrestrial ecosystem for Neanderthals than is available in this zone today. Analysis of the small‐vertebrate association from the cave reveals that the landscape surrounding the cave was dominated by woodland‐edge and open environments and that the climate was Mediterranean. The results have been compared with the only Iberian site with similar characteristics to the Cova del Gegant, Gorham's cave (southern Iberia, Gibraltar), revealing differences and similarities in the landscape and climate on the basis of the small‐mammal assemblages as well as the differences in the accessibility to terrestrial mammalian resources for the Neanderthal groups. The landscape and the climate were reasonably similar at the two sites, but the differences in the accessibility of resources for the Neanderthals are directly related to the location of the sites and the coastal position. Whereas the Cova del Gegant was on a route of mammal migration (between the Ebro Valley and France) suited for securing terrestrial resources, Gorham's cave is located on a small peninsula with a lower abundance of terrestrial mammal resources. This is probably why the Neanderthal groups at Gorham's cave exploited marine resources, whereas there is no evidence of marine resources having been exploited at Cova del Gegant, even though the seashore was nearby. Copyright © 2011 John Wiley & Sons, Ltd.
Local therapy and survival in breast cancer with distant metastases
Authors: Noguchi Masakuni , Nakano Yasuharu , Noguchi Miki , Ohno Yukako , Kosaka Takeo
Published: August 2011

This review article presents an evaluation of the effects of local therapy on survival of breast cancer patients with distant metastases along with a discussion of their relevance. Primary and recurrent breast cancers with distant metastases are systemic diseases with poor prognosis. However, several retrospective studies have demonstrated that surgical removal of the primary breast tumor has a favorable impact on the prognosis of stage IV breast cancer patients. Similarly, it has been reported that surgical resection of metastatic lesions in the lung as well as the liver yields unexpectedly promising results. The interaction of local treatment and systemic therapy may be important, because surgery and radiotherapy are only local treatments. However, it remains uncertain whether these encouraging findings are due to the surgical procedure itself or preoperative patient selection. Only a randomized prospective study can definitively show whether local treatment can prevent death from stage IV disease or recurrent breast cancer with distant metastases. Until data from prospective studies are available, clinicians must weigh retrospective experiences and clinical judgment in deciding whether to offer surgery or radiotherapy to these patients. J. Surg. Oncol. 2012; 105:104–110. © 2011 Wiley Periodicals, Inc.
Determination of darusentan enantiomers in rat plasma by enantioselective liquid chromatography with tandem mass spectrometry using cellulose‐based chiral stationary phase
Authors: Gu Jianmin , Shi Xiaowei , Du Yumin , Wang Wei , Du Xiufang , Zhang Lantong
Published: August 2011

A sensitive, specific and rapid liquid chromatography–mass spectrometry (LC‐MS/MS) method has been developed and validated for enantioselective determination of darusentan enantiomers, orally active potent endothelin‐A receptor antagonist, in rat plasma. The plasma samples were pretreated by protein precipitation with methanol and baseline chromatographic separation was performed on a Chiralcel OD‐RH column with a mobile phase consisting of acetonitrile/water/formic acid (50:50:0.1, v/v/v) at a flow rate of 0.5 mL/min. The detection was accomplished by multiple‐reaction monitoring (MRM) scanning via electrospray ionization (ESI) source operating in the negative ionization mode. The calibration curve was linear over the investigated concentration from 0.500 to 2500 ng/mL (r≥0.995) for each enantiomer using 50 μL of rat plasma. The lower limit of quantitation (LLOQ) for each enantiomer was 0.500 ng/mL. The intra‐ and inter‐day precisions were not more than 10.2% and the accuracy was within the range from −5.4 to 6.3% for darusentan enantiomers. No chiral inversion was observed during the plasma preparation, storage and analysis. The method proved adequate for enantioselective pharmacokinetic studies of darusentan enantiomers after oral administration of three different doses of racemic darusentan.
Alkaloids in the human food chain – Natural occurrence and possible adverse effects
Authors: Koleva Irina I. , van Beek Teris A. , Soffers Ans E. M. F. , Dusemund Birgit , Rietjens Ivonne M. C. M.
Published: August 2011

Alkaloid‐containing plants are an intrinsic part of the regular Western diet. The present paper summarizes the occurrence of alkaloids in the food chain, their mode of action and possible adverse effects including a safety assessment. Pyrrolizidine alkaloids are a reason for concern because of their bioactivation to reactive alkylating intermediates. Several quinolizidine alkaloids, β‐carboline alkaloids, ergot alkaloids and steroid alkaloids are active without bioactivation and mostly act as neurotoxins. Regulatory agencies are aware of the risks and have taken or are considering appropriate regulatory actions for most alkaloids. These vary from setting limits for the presence of a compound in feed, foods and beverages, trying to define safe upper limits, advising on a strategy aiming at restrictions in use, informing the public to be cautious or taking specific plant varieties from the market. For some alkaloids known to be present in the modern food chain, e.g. piperine, nicotine, theobromine, theophylline and tropane alkaloids risks coming from the human food chain are considered to be low if not negligible. Remarkably, for many alkaloids that are known constituents of the modern food chain and of possible concern, tolerable daily intake values have so far not been defined.
Acrolein‐mediated injury in nervous system trauma and diseases
Authors: Shi Riyi , Rickett Todd , Sun Wenjing
Published: August 2011

Acrolein, an α,β‐unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4‐hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis. Acrolein may overwhelm the anti‐oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury. Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein‐mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment, which is primed for rapid translation to the clinic.
Prevalence of self‐reported double incontinence in the Urban population of a Brazilian city
Authors: Santos Claudia Regina de Souza , Santos Vera Lúcia Conceição de Gouveia
Published: August 2011

Aims

To determine the prevalence, and sociodemographic and clinical factors associated with combined fecal and urinary incontinence in adults living in Pouso Alegre, Minas Gerais, Brazil.

Methods

This epidemiological study was approved by the Research Ethics Committee of the University of São Paulo School of Nursing. The participants were selected using a stratified cluster sampling design. The final sample consisted of 519 individuals, randomly selected, aged ≥18 years, living in 341 households in the urban area. Prevalence was adjusted for age and gender.

Results

The total prevalence of double incontinence was 3.0% (men 1.0%; women 5.0%). The results of the final logistic regression model showed that changes in the habit of going out (odds ratio = 62.2; P < 0.001), duration of incontinence (odds ratio = 39.2; P < 0.001), female gender (odds ratio = 21.6; P < 0.001), and widowhood (odds ratio = 19.4; P < 0.001) were associated with the presence of double incontinence.

Conclusion

The study allowed a better understanding of the epidemiology of double incontinence and may contribute to the development of public policies and programs for primary and secondary prevention and treatment of double incontinence, at least at the municipal level. Neurourol. Urodynam. Neurourol. Urodynam. 30: 1473–1479, 2011. © 2011 Wiley Periodicals, Inc.
Pelvic floor muscle and transversus abdominis activation in abdominal hypopressive technique through surface electromyography
Authors: Stüpp Liliana , Resende Ana Paula Magalhães , Petricelli Carla Dellabarba , Nakamura Mary Uchiyama , Alexandre Sandra Maria , Zanetti Miriam R. Diniz
Published: August 2011

Aims

The abdominal hypopressive technique (AHT) is performed mainly via transversus abdominis (TrA) activation and has been indicated for pelvic floor muscle (PFM) disorders. In some European countries, this technique has become widely used. This study aimed to investigate PFM and TrA activation during the AHT through surface electromyography.

Methods

Thirty‐four nulliparous physical therapists in good general health were asked to participate in the trial. To ascertain a correct PFM contraction, each of the participants was assessed by inspection and digital palpation. Ability to contract the TrA was assessed by surface electromyography and AHT training was given before analysis. TrA and PFM activity was recorded using surface electromyography.

Results

The mean age of the volunteers was 28.1 (±6.0) years and the mean body mass index was 23.7 (±3.3) kg/m2. More than half of the volunteers were physically active (61.3%) and regularly performed PFM training (52.9%) but not TrA exercises (58.8%). Although the AHT activates the PFM when compared to resting tone (P < 0.001), this method is significantly less effective than PFM alone (P < 0.001). Additionally, the combination of the two techniques (AHT + PFM) was similarly effective as isolated PFM contraction (P = 0.586). Although the AHT activated the TrA significantly more than did PFM alone (P = 0.002), the addition of PFM contraction to the AHT significantly increased the amount of TrA activation (P < 0.001).

Conclusions

Based on our results, the AHT is less effective than PFM contraction alone, and adding PFM contraction to AHT also improves the TrA contraction. Neurourol. Urodynam. Neurourol. Urodynam. 30: 1518–1521, 2011. © 2011 Wiley Periodicals, Inc.
The effect of intravesical acetylsalicylic acid instillation on tissue prostaglandin levels after partial bladder outlet obstruction in rabbits
Authors: Kibar Yusuf , Irkilata Hasan C. , Yaman Halil , Onguru Onder , Coguplugil Adem E. , Ergin Giray , Seyrek Melik , Yildiz Oguzhan , Dayanc Murat
Published: August 2011

Aims

To examine whether obstruction changes the expression of prostaglandins (PGs) in bladder, intravesical low‐dose aspirin could be used as a new route of drug administration, this way of administration influences PGs' expression, and contractile function of the bladder is protected after treatment.

Methods

Eighteen rabbits were divided into three groups. Sham‐operated group (group 1) included 6 rabbits. Twelve rabbits were partially obstructed for 70 days. Six of these 12 rabbits not receiving any treatment constituted obstructed group (group 2). The remaining six rabbits received 2 mg/kg/day aspirin (group 3). One rabbit in each group was evaluated on 1st, 7th, 14th, 28th, 42nd, and 70th days following obstructive surgery. After scarification, the percentage of collagenous area and concentrations of PGE2 and PGF2‐alpha were measured. Contractile responses to field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined.

Results

Wet tissue PGE2 and PGF2‐alpha levels were higher in obstructed group than the other groups. Aspirin decreased the percentage of collagenous area in group 3 compared to the group 2, but this difference was not statistically significant. The strips from aspirin groups resulted in better contractile response to cholinergic stimulation with KCl, but this difference was not statistically significant between the obstructed and aspirin groups. Similarly, carbachol did not elicit significantly greater concentration‐dependent contraction in strips from obstructed group compared to those from aspirin groups. Maximum responses to EFS were not significant in aspirin group compared to those from obstructed group.

Conclusions

Intravesical aspirin may have protective effect on partially obstructed bladder. Neurourol. Urodynam. Neurourol. Urodynam. 30: 1646–1651, 2011. © 2011 Wiley Periodicals, Inc.
Strain‐dependent urethral response
Authors: Haworth Donna J. , Kitta Takeya , Morelli Brian , Chew Douglas W. , Yoshimura Naoki , de Groat William C. , Vorp David A.
Published: August 2011

Aims

The Sprague–Dawley (SD) rat, an out‐bred, all‐purpose strain, has served well for lower urinary tract research. However, to test new cellular therapies for conditions such as stress urinary incontinence, an in‐bred rat strain with immune tolerance, such as the Lewis rat, may be more useful. The objective of this study was to reveal any differences in lower urinary tract continence mechanisms between the Lewis and SD rat.

Methods

The contribution of (1) the striated and smooth muscle to the mechanical and functional properties of the urethra in vitro, and (2) the striated sphincter to leak point pressure (LPP) and reflex continence mechanisms in vivo were assessed in normal (control) Lewis and SD rats and in a model of stress urinary incontinence produced by bilateral pudendal nerve transection.

Results

Control, Lewis rats had significantly lower LPP, significantly less fast‐twitch skeletal muscle and relied less on the striated sphincter for continence than control, SD rats, as indicated by the failure of neuromuscular blockade with alpha‐bungarotoxin to reduce LPP. Nerve transection significantly decreased LPP in the SD rat, but not in the Lewis rat. Although the Lewis urethra contained more smooth muscle than the SD rat, it was less active in vitro as indicated by a low urethral baseline pressure and lack of response to phenylephrine.

Conclusions

We have observed distinct differences in functional and mechanical properties of the SD and Lewis urethra and have shown that the Lewis rat may not be suitable as a chronic model of SUI via nerve transection. Neurourol. Urodynam. Neurourol. Urodynam. 30: 1652–1658, 2011. © 2011 Wiley Periodicals, Inc.
Reducing bias in pelvic floor disorders research: Using directed acyclic graphs as an aid
Authors: Sung Vivian W.
Published: August 2011

Aims

The aim of most pelvic floor disorders (PFD) research is to obtain an unbiased effect estimate and to make causal inferences. New developments in epidemiologic research, including the use of causal directed acyclic graphs (DAGs), have shown that traditional analytical strategies for research can be inadequate, leading to unintended consequences such as introducing additional bias. Although DAGs have been proven to be useful in other medical fields, their use has been limited in PFD research. The aim of this paper is to introduce DAGs and then demonstrate their application in PFD research. This paper will also illustrate how relying purely on statistical techniques can lead to pitfalls in reducing bias in research studies.

Methods/Results

DAGs are a graphical epidemiologic tool that provide a method to select for potential confounders and minimize bias in the design and analysis of research studies. We start by providing an introduction to DAGs. We then describe six scenarios in PFD research in which DAGs can be helpful: (1) identifying appropriate confounding variables for adjustment; (2) identifying potential over‐adjustment when conditioning on a mediator; (3) identifying unintended confounding due to inappropriate adjustment; (4) identifying unintended selection bias due to inappropriate adjustment; (5) planning analyses in cross‐sectional studies; and (6) using DAGs as a framework to help plan data collection and analyses in PFD research.

Conclusions

We demonstrate how the application of DAGs as an aid to PFD research can help to decrease bias and discuss the insights and implications for study design and analytical approaches. Neurourol. Urodynam. 31:115–120, 2012. © 2011 Wiley Periodicals, Inc.
Effects of pyruvate dose on in vivo metabolism and quantification of hyperpolarized 13C spectra
Authors: Janich M. A. , Menzel M. I. , Wiesinger F. , Weidl E. , Khegai O. , Ardenkjaer‐Larsen J. H. , Glaser S. J. , Haase A. , Schulte R. F. , Schwaiger M.
Published: August 2011

Real‐time in vivo measurements of metabolites are performed by signal enhancement of [1‐13C]pyruvate using dynamic nuclear polarization, rapid dissolution and intravenous injection, acquisition of free induction decay signals and subsequent quantification of spectra. The commonly injected dose of hyperpolarized pyruvate is larger than typical tracer doses, with measurement before complete dilution of the injected bolus. Pyruvate is in exchange with its downstream metabolites lactate, alanine and bicarbonate. A transient exposure to high pyruvate blood concentrations may cause the saturation of cellular uptake and metabolic conversion. The goal of this study was to examine the effects of a [1‐13C]pyruvate bolus on metabolic conversion in vivo.

Spectra were quantified by three different methods: frequency‐domain fitting with LCModel, time‐domain fitting with AMARES and simple linear least‐squares fitting in the time domain. Since the simple linear least‐squares approach showed bleeding artifacts and LCModel produced noisier time signals. AMARES performed best in the quantification of in vivo hyperpolarized pyruvate spectra.

We examined pyruvate doses of 0.1–0.4 mmol/kg (body mass) in male Wistar rats by acquiring slice‐selective free induction decay signals in slices dominated by heart, liver and kidney tissue. Dose effects were noted in all cases, except for alanine in the cardiac slice below the dose of 0.2 mmol/kg. Our results indicate unlimited cellular uptake of pyruvate up to this dose and limited enzymatic activity of lactate dehydrogenase. In the cardiac slice above 0.2 mmol/kg and in liver and kidney slices, reflect limited cellular uptake or enzymatic activity, or a combination of both effects. The results indicate that the dose of pyruvate must be recognized as an important determinant for metabolic tissue kinetics, and saturation effects must be taken into account for the quantitative interpretation of the observed results. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of implantation site and growth of hepatocellular carcinoma on apparent diffusion coefficient of water and sodium MRI
Authors: Babsky Andriy M. , Ju Shenghong , Bennett Stacy , George Beena , McLennan Gordon , Bansal Navin
Published: August 2011

Hepatocellular carcinoma (HCC) and liver metastases are an increasing problem worldwide. Non‐invasive methods for the early detection of HCC and understanding of the tumor growth mechanisms are highly desirable. Both the diffusion‐weighted 1H (DWI) and 23Na MRI reflect alterations in tissue compartment volumes in tumors, as well as physiological and metabolic transformation in cells. Effects of untreated growth on apparent diffusion coefficient of water (ADC), single quantum (SQ) and triple quantum‐filtered (TQF) 23Na MRI were compared in intrahepatically and subcutaneously implanted HCCs in rats. Animals were examined weekly for 4 weeks after injection of N1S1 cells. ADC of intrahepatic HCC was 1.5‐times higher compared to the nearby liver tissue, and with growth, the ADC did not increase. ADC of subcutaneous HCC was lower compared to intrahepatic HCC and it increased with growth. Untreated growth of both intrahepatic and subcutaneous HCCs was associated with an increase in SQ and TQF 23Na signal intensity suggesting an increase in tissue Na+ and intracellular Na+ (Na+i), respectively, most likely due to an increase in relative extracellular space and Na+i concentration as a result of changes in tissue structure and cellular metabolism. Thus, SQ and TQF 23Na MRI may be complementary to diffusion imaging in areas susceptible to motion for characterizing hepatic tumors and for other applications, such as, predicting and monitoring therapy response. Copyright © 2011 John Wiley & Sons, Ltd.
Predicting long‐term survival and treatment response in breast cancer patients receiving neoadjuvant chemotherapy by MR metabolic profiling
Authors: Cao Maria D. , Sitter Beathe , Bathen Tone F. , Bofin Anna , Lønning Per E. , Lundgren Steinar , Gribbestad Ingrid S.
Published: August 2011

Purpose

This study aimed to evaluate whether MR metabolic profiling can be used for prediction of long‐term survival and monitoring of treatment response in locally advanced breast cancer patients during neoadjuvant chemotherapy (NAC). Methods: High resolution magic angle spinning (HR MAS) MR spectra of pre‐ and post‐treatment biopsies from 33 patients were acquired. Tissue concentrations of choline‐containing metabolites (tCho), glycine and taurine were assessed using electronic reference to access in vivo concentration (ERETIC) of the signal and receiver operating characteristic (ROC) curves was used to define their potential to predict patient survival and treatment response. The metabolite profiles obtained by HR MAS spectroscopy were related to long‐term survival and treatment response by genetic algorithm partial least squares discriminant analysis (GA PLS‐DA).

Results

Different pre‐treatment MR metabolic profiles characterized by higher levels of tCho and lower levels of lactate were observed in patients with long‐term survival (≥5 years, survivors) compared to patients who died of cancer recurrence (<5 years, non‐survivors). A significant decrease in glycerophosphocholine (GPC) post‐treatment was associated with long‐term survival (p = 0.046) and partial response (p = 0.014) to NAC. Long‐term survival was best predicted by GPC using ROC analyses (sens. 66.7%, spec. 62.5%), while taurine had the best predictive value of treatment response (sens. 72.7%, spec. 63.2%). GA PLS‐DA multivariate classification models successfully discriminated between survivors and non‐survivors, resulting in 82.7% and 90.2% cross‐validation (CV) classification accuracy, pre‐ and post‐treatment, respectively. Classification of treatment response using GA PLS‐DA was not successful for this patient cohort.

Conclusions

Our results demonstrate that HR MAS MR metabolic profiles consisting of important metabolic characteristics of breast cancer tumors could potentially assist the classification and prediction of long‐term survival in locally advanced breast cancer patients, in addition to being used as an adjunct for evaluation of treatment response to NAC. Copyright © 2011 John Wiley & Sons, Ltd.
Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma
Authors: Turaka Kiran , Shields Carol L. , Meadows Anna T. , Leahey Ann
Published: August 2011

Background

To evaluate the occurrence of second malignant neoplasms (SMN) following chemoreduction (CRD) with carboplatin, vincristine, and etoposide (CEV) as frontline therapy in patients with retinoblastoma (RB).

Prodecure

We conducted a two‐institution retrospective chart review of 245 patients with intraocular RB treated with six cycles of vincristine, carboplatin, and etoposide for treatment of intraocular retinoblastoma. Cumulative incidence of SMN was calculated with adjustment for the competing risk of death.

Results

There were 187 patients with germline retinoblastoma and 58 with non‐germline disease. External beam radiotherapy was subsequently utilized in 46 (24%) of germline cases and six (10%) of non‐germline cases. Mean follow‐up of germline and non‐germline patients was 80 and 70 months, respectively. Seven subsequent cancers were found in six patients for an overall incidence of 3% at a mean of 11 years. For germline cases, following CEV alone (n = 156), SMN were found in 4% following the RB diagnosis. We found no SMN in patients with non‐germline RB. One patient developed pineoblastoma. SMN included osteosarcoma (n = 3), rhabdomyosarcoma (n = 1), orbital and conjunctival melanoma (n = 1), low‐grade glioma (n = 1), and acute promyeloctic leukemia (n = 1). Five of the six patients with a second malignancy survive at mean of 46 months (range 15–71 months).

Conclusions

At a mean of 11 years, 4% of children with germline RB treated with CEV as frontline therapy developed SMN's. No SMN was found in non‐germline patients. Concerns regarding CEV‐induced second cancers should not deter clinicians from using life and vision preserving therapy in patients with retinoblastoma. Pediatr Blood Cancer 2012; 59: 121–125. © 2011 Wiley Periodicals, Inc.