bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial nitric oxide synthase is central to skeletal muscle metabolic regulation and enzymatic signaling during exercise in vivo
Authors: Lee-Young Robert S. , Ayala Julio E. , Hunley Charles F. , James Freyja D. , Bracy Deanna P. , Kang Li , Wasserman David H.
Published: March 2010

Endothelial nitric oxide synthase (eNOS) is associated with a number of physiological functions involved in the regulation of metabolism; however, the functional role of eNOS is poorly understood. We tested the hypothesis that eNOS is critical to muscle cell signaling and fuel usage during exercise in vivo, using 16-wk-old catheterized (carotid artery and jugular vein) C57BL/6J mice with wild-type (WT), partial (+/−), or no expression (−/−) of eNOS. Quantitative reductions in eNOS expression (∼40%) elicited many of the phenotypic effects observed in enos−/−mice under fasted, sedentary conditions, with expression of oxidative phosphorylation complexes I to V and ATP levels being decreased, and total NOS activity and Ca2+/CaM kinase II Thr286phosphorylation being increased in skeletal muscle. Despite these alterations, exercise tolerance was markedly impaired in enos−/−mice during an acute 30-min bout of exercise. An eNOS-dependent effect was observed with regard to AMP-activated protein kinase signaling and muscle perfusion. Muscle glucose and long-chain fatty acid uptake, and hepatic and skeletal muscle glycogenolysis during the exercise bout was markedly accelerated in enos−/−mice compared with enos+/−and WT mice. Correspondingly, enos−/−mice exhibited hypoglycemia during exercise. Thus, the ablation of eNOS alters a number of physiological processes that result in impaired exercise capacity in vivo. The finding that a partial reduction in eNOS expression is sufficient to induce many of the changes associated with ablation of eNOS has implications for chronic metabolic diseases, such as obesity and insulin resistance, which are associated with reduced eNOS expression.
A new approach for flow-through respirometry measurements in humans
Authors: Melanson Edward L. , Ingebrigtsen Jan P. , Bergouignan Audrey , Ohkawara Kazunori , Kohrt Wendy M. , Lighton John R. B.
Published: March 2010

Indirect whole room calorimetry is commonly used in studies of human metabolism. These calorimeters can be configured as either push or pull systems. A major obstacle to accurately calculating gas exchange rates in a pull system is that the excurrent flow rate is increased above the incurrent flow rate, because the organism produces water vapor, which also dilutes the concentrations of respiratory gasses in the excurrent sample. A common approach to this problem is to dry the excurrent gasses prior to measurement, but if drying is incomplete, large errors in the calculated oxygen consumption will result. The other major potential source of error is fluctuations in the concentration of O2and CO2in the incurrent airstream. We describe a novel approach to measuring gas exchange using a pull-type whole room indirect calorimeter. Relative humidity and temperature of the incurrent and excurrent airstreams are measured continuously using high-precision, relative humidity and temperature sensors, permitting accurate measurement of water vapor pressure. The excurrent flow rates are then adjusted to eliminate the flow contribution from water vapor, and respiratory gas concentrations are adjusted to eliminate the effect of water vapor dilution. In addition, a novel switching approach is used that permits constant, uninterrupted measurement of the excurrent airstream while allowing frequent measurements of the incurrent airstream. To demonstrate the accuracy of this approach, we present the results of validation trials compared with our existing system and metabolic carts, as well as the results of standard propane combustion tests.
Intermittent access to sucrose increases sucrose-licking activity and attenuates restraint stress-induced activation of the lateral septum
Authors: Martin Jessica , Timofeeva Elena
Published: March 2010

Intermittent access to palatable food can attenuate anorectic and hormonal responses to stress in rats. The neuronal mechanisms of modulation of stress response by diets are not fully understood. The present study was conducted to create rat models with intermittent access to sucrose that demonstrate resistance to stress-induced hypophagia, to study the pattern of sucrose consumption by these rat models, and to investigate in which brain structures intermittent sucrose regimens modify stress-induced neuronal activation. The obtained results demonstrate that 6-wk intermittent access to sucrose without food restriction (4 day/wk ad libitum access to sucrose in addition to chow, and following 3 day/wk exclusive feeding of chow; SIA rats) and combined with food restriction (4 day/wk access to chow and sucrose restricted to 2 h/day, and following 3 days/wk on unrestricted chow; SIR rats) increased sucrose-licking activity. The alterations in the rats' feeding behavior were accompanied by a resistance of their body weight gain and food intake to 1-h restraint stress applied once per week. The chronic intermittent sucrose consumption significantly lowered, in the SIA and SIR rats, the levels of expression of corticotropin-releasing factor type 2 receptor and restraint stress-induced expression of c- fos mRNA in the medioventral part of the lateral septum. Conversely, the levels of the corticotropin-releasing factor type 2 receptor transcript in the ventromedial hypothalamic nucleus were decreased only in the food-restricted SIR rats. The lower stress-induced neuronal activation in the medioventral part of the lateral septum may contribute to the attenuated anorectic stress response in the rats maintained on intermittent sucrose regimens.
Expiratory flow limitation during exercise in prepubescent boys and girls: prevalence and implications
Authors: Swain Katherine E. , Rosenkranz Sara K. , Beckman Bethany , Harms Craig A.
Published: March 2010

The purpose of this study was to compare the prevalence and implications of expiratory flow limitation (EFL) during exercise in boys and girls. Forty healthy, prepubescent boys (B; n = 20) and girls (G; n = 20) were tested. Subjects completed pulmonary function tests and an incremental cycle maximal oxygen uptake (V̇o2max) test. EFL was recorded at the end of each exercise stage using the % tidal volume overlap method. Ventilatory and metabolic data were recorded throughout exercise. Arterial oxygen saturation (SpO2) was determined via pulse oximetry. Body composition was determined using dual-energy X-ray absorptiometry. There were no differences ( P > 0.05) in height, weight, or body composition between boys and girls. At rest, boys had significantly higher lung volumes (total lung capacity, B = 2.6 ± 0.5 liters, G = 2.1 ± 0.5 liters) and peak expiratory flow rates (B = 3.6 ± 0.6 l/s; G = 1.6 ± 0.3 l/s). Boys also had significantly higher V̇o2max (B = 46.9 ± 5.9 ml·kg lean body mass−1·min−1, G = 41.7 ± 6.6 ml·kg lean body mass−1·min−1) and maximal ventilation (B = 49.8 ± 8.8 l/min, G = 41.2 ± 8.3 l/min) compared with girls. There were no sex differences ( P > 0.05) at V̇o2max in VE /Vco2, end-tidal Pco2, heart rate, respiratory exchange ratio, or SpO2. The prevalence (B = 19/20 vs. G = 18/20) and severity (B = 58 ± 7% vs. G = 43 ± 8% tidal volume) of EFL was not significantly different in boys compared with girls at V̇o2max. A significant relationship existed between % EFL at V̇o2max and the change in end-expiratory lung volume from rest to maximal exercise in boys ( r = 0.77) and girls ( r = 0.75). In summary, our data suggests that EFL is highly and equally prevalent in prepubescent boys and girls during heavy exercise, which led to an increased end-expiratory lung volume but not to decreases in arterial oxygen saturation.
Pulsed Noise Experience Disrupts Complex Sound Representations
Authors: Insanally Michele N. , Albanna Badr F. , Bao Shaowen
Published: March 2010

Cortical sound representations are adapted to the acoustic environment. Early exposure to exponential frequency-modulated (FM) sweeps results in more neurons selective to the experienced sounds. Here we examined the influence of pulsed noise experience on the development of sound representations in the primary auditory cortex (AI) of the rat. In naïve animals, FM sweep direction selectivity depends on the characteristic frequency (CF) of the neuron—low CF neurons tend to select for upward sweeps and high CF neurons for downward sweeps. Such a CF dependence was not observed in animals that had received weeklong exposure to pulsed noise in periods from postnatal day 8 (P8) to P15 or from P24 to P39. In addition, AI tonotopicity, tuning bandwidth, intensity threshold, tone-responsiveness, and sweep response magnitude were differentially affected by the noise experience depending on the exposure time windows. These results are consistent with previous findings of feature-dependent multiple sensitive periods. The different effects induced here by pulsed noise and previously by FM sweeps further indicate that plasticity in cortical complex sound representations is specific to the sensory input.
Clinical Presentation of a Patient with Localized Acquired Cutis Laxa of Abdomen: A Case Report
Authors: Gverić Tugomir , Barić Marko , Bulat Vedrana , Šitum Mirna , Pušić Jana , Huljev Dubravko , Zdilar Boris , Gverić-Ahmetašević Snježana , Tomas Davor
Published: March 2010

Background. Cutis laxa (CL) is a rare disorder of elastic tissue characterized by loose, sagging skin with reduced elasticity, and resilience without resulting scarring. CL may be inherited as a dominant, recessive, or X‐linked recessive disease, or acquired. The heritable forms of CL predominantly begin at birth, but it may be delayed until puberty or age of 30 years with extracutaneous manifestations including pulmonary emphysema, umbilical and inguinal hernias, and gastrointestinal and vesicourinary tract diverticuli. An acquired form of the disease occurs in adults with no evidence of internal organ involvement. Objective. The aim of this case report was to present our patient suffering from CL, and to evaluate clinical presentation, diagnostic and therapeutic difficulties in this rare condition. Case Report. A 30‐year‐old female patient was admitted to our Hospital due to localized loose and sagging skin of abdomen, induced by prior cesarean section 6 years ago. CL has been diagnosed based on the clinical picture and pathohistological appearance. Conclusion. Reconstructive surgery provides a dramatic cosmetic improvement with significant psychosocial benefit. Repeated surgical procedures may be required to correct the lax skin, which worsens with age.
Occlusion of Internal Carotid Artery in Kimura's Disease
Authors: Tamaki Tomonori , Yoji Node
Published: March 2010

We describe a unique case of Kimura's disease in which cerebral infarction was caused by occlusion of the right internal carotid artery. A 25-year-old man with Kimura's disease was admitted to our hospital because of left hemiparesis. Computed tomography and magnetic resonance imaging of the head showed infarction in the right frontal and temporal lobes. Cerebral angiography demonstrated right internal carotid artery occlusion affecting the C1 segment, with moyamoya-like collateral vessels arising from the right opthalamic artery. Kimura's disease is a chronic disease characterized by the clinical triad of slowly enlarging subcutaneous masses with lymphoid hyperplasia in the head and neck. It often occurs in young Asian men. In our patient, the pathogenesis of internal carotid artery occlusion was unknown. There have only been a few case reports in which occlusion of the internal carotid artery was associated with autoimmune disease, and no previous cases of internal carotid occlusion associated with Kimura's disease have been reported. We suspected that occlusion of this patient's internal carotid artery may be caused by the autoimmune mechanism that underlies Kimura's disease.
Retained Intraabdominal Gossypiboma, Five Years after Bilateral Orchiopexy
Authors: Moslemi Mohammad Kazem , Abedinzadeh Mehdi
Published: March 2010

Introduction.Gossypiboma or textiloma is used to describe a retained surgical swab in the body after an operation. Intraabdominal surgical sponge is an uncommon surgical error. The incidence of gossypiboma has been reported as high as 1 in 1000 to 15,000 intraabdominal operations. Gossypiboma may cause serious morbidity and may lead to mortality.Case presentation.Herein, we report a 24 years-old man who was admitted due to the intraabdominal mass after evaluation of primary infertility. He had a surgical history of bilateral abdominal orchiopexy 5 years previously, performed at another hospital. Hydatid cyst was suspected by abdominal computed tomography. After laparotomy excision, the cyst wall opened incidentally, and draining of a large amount of thick pus with retained surgical gauze within the cyst was found, with final diagnosis of gossypiboma.Conclusion.The policy that prevention is far more important than cure is highly appreciated. Accurate sponge and instrument counts, along with radiologic evaluation when a discrepancy is found, can be helpful. Although human errors cannot be completely avoided, continuous medical training and strict adherence to rules of the operation room should reduce the incidence of gossypiboma to a minimum. Surgical sponges should be counted once at the start and twice at the end of all surgical operations.
The Adenovirus Type 3 Dodecahedron's RGD Loop Comprises an HSPG Binding Site That Influences Integrin Binding
Authors: Gout E. , Schoehn G. , Fenel D. , Lortat-Jacob H. , Fender P.
Published: March 2010

Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases) features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs) and integrins interaction and is used as a versatile vector to deliver DNA or proteins. Cryo-EM reconstruction of the pseudoviral particle with Heparan Sulphate (HS) oligosaccharide shows an extradensity on the RGD loop. A set of mutants was designed to study the respective roles of the RGD sequence (RGE mutant) and of a basic sequence located just downstream. Results showed that the RGE mutant binding to the HS deficient CHO-2241 cells was abolished and unexpectedly, mutation of the basic sequence (KQKR to AQAS) dramatically decreased integrin recognition by the viral pseudoparticle. This basic sequence is thus involved in integrin docking, showing a close interplay between HSPGs and integrin receptors.
Application of “omics” to Prion Biomarker Discovery
Authors: Huzarewich Rhiannon L. C. H. , Siemens Christine G. , Booth Stephanie A.
Published: March 2010

The advent of genomics and proteomics has been a catalyst for the discovery of biomarkers able to discriminate biological processes such as the pathogenesis of complex diseases. Prompt detection of prion diseases is particularly desirable given their transmissibility, which is responsible for a number of human health risks stemming from exogenous sources of prion protein. Diagnosis relies on the ability to detect the biomarkerPrPSc, a pathological isoform of the host proteinPrPC, which is an essential component of the infectious prion. Immunochemical detection ofPrPScis specific and sensitive enough for antemortem testing of brain tissue, however, this is not the case in accessible biological fluids or for the detection of recently identified novel prions with unique biochemical properties. A complementary approach to the detection ofPrPScitself is to identify alternative, “surrogate” gene or protein biomarkers indicative of disease. Biomarkers are also useful to track the progress of disease, especially important in the assessment of therapies, or to identify individuals “at risk”. In this review we provide perspective on current progress and pitfalls in the use of “omics” technologies to screen body fluids and tissues for biomarker discovery in prion diseases.
Benign Intraductal Papillary-Mucinous Neoplasm of the Pancreas Associated with Spontaneous Pancreaticogastric and Pancreaticoduodenal Fistulas
Authors: Jausset F. , Delvaux M. , Dumitriu D. , Bressenot A. , Bruot O. , Mathias J. , Regent D. , Laurent V.
Published: March 2010

Invasive intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas may be associated with pancreaticogastric fistulas as shown by case reports. We report the case of a benign IPMN associated with pancreaticogastric and pancreaticoduodenal fistulas. A 70-year-old woman was admitted with intestinal obstruction. Computed tomography and MRI showed a large dilatation of the main pancreatic duct (>1 cm) with intraductal nodules, and pancreaticogastric and pancreaticoduodenal fistulas. Several features in imaging were present to support a malignant IPMN, so that the patient underwent a pancreaticoduodenectomy. The histopathological examination of the surgical specimen showed a benign IPMN. This case proves that a benign IPMN can cause pancreaticogastric and pancreaticoduodenal fistulas, probably resulting from mechanical factors.
Visceral versus Somatic Pain: Similarities and Differences
Authors: Cervero Fernando
Published: March 2010

Inflammatory bowel disease and the irritable bowel syndrome are conditions characterized by chronic pain that generates persistent, hyperalgesic states in many regions of the body. It is difficult to explain the pain of conditions such as inflammatory bowel disease and irritable bowel syndrome by extrapolating directly from what is known about the mechanisms of somatic pain. Visceral and somatic pain show many differences not only in the psychophysics of the sensation, but also in the neurobiological mechanisms that mediate the sensory process. The activation and sensitization of visceral nociceptors are heavily influenced by the secretory and motor properties of the microenvironment where the sensory receptors are located. In some cases, epithelial cells can play a direct role in the activation of primary sensory neurons. Subclinical alterations of the epithelium can contribute to enhanced visceral sensitivity. Central hypersensitivity induced by visceral activation also shows differences with its somatic counterpart. Mobilization of AMPA receptors from the cytosol to the membrane of nociceptive neurons has been identified as a mechanism of sensitization of visceral pain pathways. Finally, functional pain syndromes, such as irritable bowel syndrome could be triggered or maintained by hormonal alterations, particularly those involving sex hormones such as estrogen.
The Role of Emotion in Determining Pain
Authors: Bass Christopher
Published: March 2010

One of the perplexing features of pain is the wide variety in patients’ responses to ostensibly the same extent of physical pathology. One reason for this is that emotional states (feelings) and thoughts (cognitions) mediate our pain perception. Furthermore, it has been shown that maintenance of pain and disability as well as response to treatment is related to a number of factors such as self-efficacy beliefs and fear avoidance. Indeed, it has been shown that these pain-related beliefs are more important determinants of disability and functioning in some disorders than pain intensity or duration. This chapter attempts to outline the role of predisposing, precipitating and maintaining factors in patients with chronic pain. The importance of a multi-dimensional assessment of patients with pain that takes into account factors such as specific feelings (emotions), thoughts (cognitions), pain behaviours and pain-coping strategies is emphasised. The key role in certain patients of ‘catastrophising’, as well as causal beliefs and attributions on pain outcomes and disability, will be outlined. It is useful to adopt a ‘stepped care’ approach to treatment. Most patients with irritable bowel syndrome will respond to reassurance, whereas those with more enduring and/or difficult to manage symptoms may require treatments of a different type and level of complexity. This may include antidepressant drug treatment or, in certain situations, cognitive behavioural treatment. It is quite acceptable to adopt more than one treatment approach concurrently. Antidepressant treatment has also been shown to be effective in concert with psychological treatments and to lead to improved quality of life.
Inflammation, Peptides and Biological Therapy
Authors: Atreya Raja , Neurath Markus F.
Published: March 2010

Inflammatory bowel diseases are characterized by chronic relapsing inflammations of the gastrointestinal tract that are not caused by specific pathogens. Although the precise aetiology of inflammatory bowel diseases remains unclear, considerable progress has been made in the identification of critical cytokine mediated signalling pathways in the inflammatory process. It could be shown that these pathways induce augmented intestinal T cell resistance against apoptosis, which is a pivotal process in disease pathogenesis. These findings have facilitated our understanding of the disease and the development of new therapies, which aim at restoring mucosal T cell homeostasis based on a sound pathophysiological rationale. This development is best exemplified by the emergence of anti-tumour necrosis factor antibody therapy. The advent of other biological therapies, such as the anti-IL-6R antibody, offers hope for new strategies that may result in more effective and less toxic therapy.
Experimental Models of Stress and Pain: Do They Help to Develop New Therapies?
Authors: Bradesi Sylvie , Mayer Emeran A.
Published: March 2010

The majority of functional gastrointestinal disorders are characterised by recurrent abdominal pain, with stress playing an important role in first onset and exacerbation of existing symptoms. These disorders are currently defined by symptom criteria, while their pathophysiology remains controversial and incompletely understood. Modeling these disorders in humans and animals has been difficult. While some of the models have adequate face and construct validity, the predictive validity of most of the models has been disappointing, which has put into question the traditional modeling approach. Similar problems have been encountered in drug development for pain and psychiatric disorders. New approaches have been proposed in the form of reverse translation, which include better characterisation of biological intermediate phenotypes in human disease which can be modeled in humans and in animals. Continuation of the current approach focusing on complex clinical phenotypes is likely to be ineffective for the development of novel and effect treatments.
How to Avoid Treating Irritable Bowel Syndrome with Biologic Therapy for Inflammatory Bowel Disease
Authors: Sandborn William J.
Published: March 2010

Some patients with an established diagnosis of Crohn’s disease and symptoms compatible with a disease flare do not have evidence of active Crohn’s disease by laboratory, endoscopic or radiographic criteria. In clinical trials, approximately 18% of patients with Crohn’s disease and moderate to severe clinical symptoms have no evidence of ulceration at colonoscopy. There are multiple other causes of symptoms in patients with Crohn’s disease, including the presence of disease complications (stricture, fistula and abscess), complications of surgical resection (bile salt diarrhea, steatorrhoea and small bowel bacterial overgrowth), concomitant irritable bowel syndrome, concomitant infections (Clostridium difficile, cytomegalovirus) and concomitant depression. In conclusion, the clinical impression of gastroenterologists based on the patient’s history is frequently incorrect and is an insufficient basis for making therapeutic decisions. Colonoscopy and CT or MRI enterography should be employed routinely prior to any major changes in therapy: (1) before starting steroids, immunosuppressives or biologicals; (2) when patients fail to respond to steroids, immunosuppressives or biologicals; (3) when patients receiving maintenance therapy with immunosuppressives or biologicals relapse; (4) before surgery. Treatment of patients who have no evidence of active disease by imaging with steroids, immunosuppressives or biological agents will not address the cause of the symptoms and will expose the patient to risks that may be unnecessary. These patients should be systematically evaluated for bile acid diarrhoea, steatorrhoea, bacterial overgrowth, irritable bowel syndrome and depression.
Yeasts: Neglected Pathogens
Authors: Poulain Daniel , Sendid Boualem , Standaert-Vitse Annie , Fradin Chantal , Jouault Thierry , Jawhara Samir , Colombel Jean-Frederic
Published: March 2010

Background: Current research on Crohn’s disease (CD) concerns molecular events related to loss of tolerance to microbes that could trigger or maintain inflammation in genetically susceptible individuals. CD is also associated with antimicrobial antibodies, including the antibodies we described against yeast oligomannosides (ASCA). This prompted us to investigate a role for another yeast, Candida albicans, a very common commensal of the human digestive tract and an important opportunistic pathogen. Clinical and Experimental Data: It has been revealed that the major oligomannose epitopes supporting ASCA are expressed by C. albicans in human tissues, suggesting that C. albicans is the immunogen for ASCA. This link has been reinforced by the demonstration that novel serological markers of CD (ALCA and ACCA), consisting of antibodies against chitin and glucan (two components of the C. albicans cell wall), are also generated during C. albicans infection. Mycological investigation of families with multiple cases of CD shows that patients with CD and their healthy relatives are colonized with C. albicans more commonly than control families. In healthy relatives, C. albicans colonization correlates with ASCA levels, whereas the onset of CD is associated with ASCA stability and is independent of the C. albicans intestinal load. Experimental studies show that chemically-induced colitis promotes C. albicans colonization in mice. In turn, C. albicans colonization generates ASCA, increases inflammation, histological scores and pro-inflammatory cytokine expression. Perspectives: Current investigations focus on interactions of TLRs and lectins with yeast epitopes that differently polarize the immune response to C. albicans cell wall glycans, which are the targets of an ‘excessive’ adaptive response associated with CD.
Probiotics for Inflammatory Bowel Disease: A Critical Appraisal
Authors: Sans Miquel
Published: March 2010

The notion that the intestinal microbiota plays a key role for the development of intestinal inflammation, initially based on a series of clinical observations both in human inflammatory bowel disease and experimental colitis, has been reinforced by a growing body of evidence demonstrating that the abnormal recognition of bacterial and other microbiota antigens by the innate immune system is one of the earliest events in the pathogenesis of inflammatory bowel disease. In keeping with our present knowledge of inflammatory bowel disease pathophysiology, the search for therapeutic approaches aimed at modifying the composition of the intestinal microbiota to obtain new, more targeted treatments for inflammatory bowel disease that are basically free of side effects has been a subject of intense research activity. Probiotics are defined as live organisms capable of conferring health benefits beyond their nutritional properties. Numerous micro-organisms have been evaluated to induce or maintain remission, or both, in ulcerative colitis, Crohn’s disease and pouchitis. Overall, probiotics have successfully demonstrated some efficacy in some inflammatory bowel disease scenarios. However, a critical review of the available scientific literature shows that: (1) in spite of great expectations, reflected by a high number of review and editorial articles in top journals, the number of published, well-designed clinical trials using probiotics in inflammatory bowel disease is small, often with few patients; (2) the range of microbial agents makes it particularly difficult to draw global conclusions; (3) the quality of the evidence on the efficacy of probiotics in pouchitis is clearly better than that in ulcerative colitis, while there is virtually no evidence of probiotic efficacy in Crohn’s disease. The appropriate selection of probiotic agents combined with convincing clinical trials will determine whether probiotics can jump from promise to reality in inflammatory bowel disease clinical practice.
Eosinophilic Esophagitis
Authors: Furuta Glenn T.
Published: March 2010

Eosinophilic esophagitis is a clinicopathological disease characterized by GERD-like symptoms, food impaction and dysphagia that occur with the histological finding of dense esophageal eosinophilia. Endoscopic features include linear furrows, white exudate and longitudinal shearing. Current concepts regarding the pathophysiology relate to a food allergen-induced overexpression of eosinophil-related cytokines including Il-5, IL-13 and eotaxin-3. Effective treatments include topical and systemic corticosteroids and dietary restrictions.
Mast Cells and Mastocytosis
Authors: Söderholm Johan D.
Published: March 2010

Mast cells (MCs) typically reside at barrier sites of the body, including the intestinal mucosa, and play a vital role in innate host defence. Activated MCs release a wide variety of bioactive mediators. These include preformed mediators stored in the granules (e.g. histamine and tryptase) and newly synthesised mediators (e.g. prostaglandins, leukotrienes and cytokines). MCs are present in all layers throughout the gastrointestinal (GI) tract and there is a close bi-directional connection between MCs and enteric nerves that is of vital importance in the regulation of GI functions. Some gain-of-function mutations in c-kit, encoding the tyrosine kinase- receptor for stem cell factor, are associated with the rare disease entity, systemic mastocytosis. These patients present symptoms arising from MC mediator release or infiltration. GI manifestations are common in this patient group, mainly abdominal pain and diarrhoea. Endoscopy with biopsies reveals MC infiltration in the mucosa. Other diagnostic tools include bone marrow biopsy and serum tryptase. Treatment is symptomatic with antihistamines or cromoglycate in mild cases, whereas severe cases need cytoreductive therapy that should be managed with expert haematologists. From a day-to-day clinical perspective, the important role of MCs in neuroimmune interaction has been implicated in the intestinal response to stress, in alterations of mucosal and neuromuscular function in irritable bowel syndrome or inflammatory bowel disease, and in the pathogenesis of non-erosive oesophageal reflux disease. Thus, MCs have important regulatory and protective roles in innate defence, in addition to being a potential mediator of mucosal pathophysiology in GI diseases. We need to learn how to balance the response of these volatile cells to be able to benefit from their versatility.
Collagenous and Lymphocytic Colitis: Systematic Review and Update of the Literature
Authors: Temmerman F. , Baert F.
Published: March 2010

Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female predominance mainly in collagenous colitis is observed. Both conditions are characterised by a (near) normal colonoscopy, but with specific histologic findings on colonic biopsies. Histopathologically, both conditions are characterised by distinct epithelial abnormalities and a dense lymphoplasmocytic infiltrate. Distinct features consist of a characteristic collagen band deposition in the subepithelial layer in collagenous colitis and a markedly increased number of intra-epithelial lymphocytes in lymphocytic colitis. Although most cases are idiopathic, certain drugs can induce microscopic colitis. In addition, either condition can be associated with coeliac disease. For a long time patients with microscopic colitis were treated with non-specific anti-diarrhoeal agents, anti-inflammatory agents such as mesalazine, or systemic steroids, but with disappointing results. Bismuth subsalicylate was reported to be effective in a small controlled series of patients with collagenous colitis. Now, randomised controlled trials have shown the effectiveness of budesonide over placebo in collagenous colitis and more recently in lymphocytic colitis. The histologic response is variable, but a decrease in the subepithelial collagen layer and a decrease in the lymphoplasmocytic infiltrate in the lamina propria is observed in about half of the patients. In general, patients respond within 2 weeks with no major side effects. However, relapse is common (63–80% of patients) when budesonide is stopped. Longer-term treatment is effective but does not seem to reduce relapse rates upon discontinuation.
Influence of Recanalization on Uric Acid Patterns in Acute Ischemic Stroke
Authors: Hong Ji Man , Bang Oh Young , Chung Chin-Sang , Joo In Soo , Gwag Byoung Joo , Ovbiagele Bruce
Published: March 2010

Background: Most epidemiological studies have reported a significant association between elevated serum levels of uric acid (UA) and increased cardiovascular disease. On the other hand, UA is the most abundant antioxidant in the human body. We hypothesized that UA levels would change noticeably in association with the degree of oxidative stress in acute ischemic stroke. Methods: We analyzed consecutive patients with acute ischemic stroke in the anterior circulation system within 24 h of symptom onset, confirmed by diffusion-weighted imaging (DWI), and with a modified NIH Stroke Scale (mNIHSS) score of 5 or greater. Baseline demographics, serial clinical scores, serial UA and allantoin (a nonenzymatic metabolite of UA) levels, UA change (baseline UA – UA at 48 h), and DWI lesion volumes were compared between 45 patients with recanalized vessels (RV) and 43 patients with nonrecanalized vessels (NV) in follow-up imaging. Results: The RV (vs. NV) patients were more likely to receive thrombolytic treatment (p = 0.005), achieve a reduction in day-14-mNIHSS scores (p = 0.001), and greater changes in UA (p = 0.024) and allantoin levels (p = 0.003). The UA levels dropped at 48 h and gradually increased in a U-shaped pattern. UA change (r = 0.360; p = 0.001) rather than baseline UA (r = 0.044; p = 0.681) was significantly correlated with infarct volume. In the RV (vs. NV) patients, there was a stronger association between infarct volume and UA change (r = 0.483; p = 0.001) or allantoin levels (r = 0.466; p = 0.017). Conclusion: Our results suggest that UA might be a consumptive and reproducible antioxidant in acute ischemic stroke, and this pattern appears to be influenced by recanalization success and infarct volume size.
Cerebral Venous Thrombosis with Nonhemorrhagic Lesions: Clinical Correlates and Prognosis
Authors: Ferro José M. , Canhão Patrícia , Bousser Marie-Germaine , Stam Jan , Barinagarrementeria Fernando , Stolz Erwin ,   for the ISCVT Investigators
Published: March 2010

Background and Purpose: Brain imaging of patients with acute cerebral venous thrombosis often shows parenchymal hemorrhagic and nonhemorrhagic lesions. The clinical relevance of nonhemorrhagic lesions is poorly known. Method: In the International Study on Cerebral Vein and Dural Sinus Thrombosis cohort, demographic, clinical, risk factor, prognosis and imaging findings were compared between patients with parenchymal nonhemorrhagic lesions and no hemorrhagic lesions (NHL) and (1) patients with parenchymal hemorrhagic lesions (HL) and (2) patients without brain lesions. Predictors of prognosis at the end of follow-up in the NHL group were analyzed by bivariate and Cox regression methods. Results: We identified 147 patients (23.6%) with NHL. When compared to patients without brain lesions (n = 309), those with NHL more often presented mental status disturbances, aphasia, decreased alertness, motor deficits, seizures, occlusions of the straight sinus, deep venous system and cortical veins. Patients with NHL had a better prognosis in the acute phase and at the end of follow-up than those with HL, but a worse one than patients without brain lesions, as more NHL patients were dead or dependent (modified Rankin Scale score = 3–6) at discharge (19.7 vs. 6.5%, p < 0.001) and final follow-up (14.3 vs. 7.4%, p = 0.03). In Cox regression analysis, coma (HR = 13.7; 95% CI = 4.3–43.7) and thrombosis of the deep venous system (HR = 3.5; 95% CI = 1.4–8.7) were associated with death or dependency at the end of follow-up. Conclusion: Cerebral venous thrombosis patients with NHL are intermediate between patients without brain lesions and those with HL, both in initial clinical picture and prognosis.
Characteristics of Progesterone Changes in Women with Subtle Progesterone Rise in Recombinant Follicle-Stimulating Hormone and Gonadotropin-Releasing Hormone Antagonist Cycle
Authors: Seow Kok-Min , Lin Yu-Hung , Hsieh Bih-Chwen , Huang Lee-Wen , Huang Shih-Chia , Chen Chin-Yu , Chen Pei-Hsin , Tzeng Chii-Ruey , Hwang Jiann-Loung
Published: March 2010

Background: To assess the characteristics of progesterone (Prog) changes in women with a subtle Prog rise in recombinant follicle-stimulating hormone (r-FSH) and GnRH antagonist cycles. Methods: We enrolled 233 patients undergoing controlled ovarian hyperstimulation with r-FSH and GnRH antagonist for IVF or ICSI. A subtle Prog rise 1 day before hCG administration was defined as a Prog value of ≧1.2 ng/ml. Results: 100 of 233 cycles (42.9%) showed a subtle Prog rise in this study. The mean serum Prog levels and area under curve (AUC) in the group with Prog ≧1.2 ng/ml was significantly higher than that in the Prog <1.2 ng/ml group on cycle day 8 (1.17 ± 0.4 and 0.80 ± 0.3 ng/ml, respectively, for Prog level, p = 0.003; 571 ± 123 and 763 ± 250 for AUC, p = 0.001), and remained significantly higher until the day of hCG administration. Moreover, 55% of the patients on cycle day 9, 65% on cycle day 10, 75% on cycle day 11 and 85% on cycle day 12 in the Prog ≧1.2 ng/ml group have a serum Prog level of ≧1.2 ng/ml. Conclusion: A subtle Prog rise may occur as early as cycle day 8 in r-FSH/GnRH antagonist cycles.
Spontaneous Hepatic Rupture in a Normotensive Monoamniotic Twin Pregnancy: Case Report and Review of the Literature
Authors: DeKoninck P.L.J. , Loquet P. , Leyman P. , Van Leemput J. , d’Archambeau O. , Van Wiemeersch J. , Devlieger R.
Published: March 2010

Background: Spontaneous liver rupture during pregnancy is extremely rare, and often associated with hypertensive disorders. Maternal outcomes are poor and morbidity is high. Case: A 27-year-old women (G1P0), pregnant with monochorionic-monoamniotic twins, developed extensive abdominal pain while she was electively admitted at 32 weeks for fetal pulmonary maturation. Diagnosed with preterm labor, a caesarean section was performed. Postoperatively, our patient deteriorated and a second laparotomy revealed an extensive liver rupture. There was no evidence of hypertensive disorders or hepatic tumors. After perihepatic packing and embolization, our patient required long-term treatment in our intensive care unit. She survived, and both mother and children are healthy after 6 months. Conclusion: Despite being rare, spontaneous liver rupture in absence of hypertensive disorders during pregnancy is associated with high maternal morbidity and mortality. Adequate treatment requires a multidisciplinary approach.
Biological Therapies for Cardiac Arrhythmias
Authors: Cho Hee Cheol , Marbán Eduardo
Published: March 2010

Abstract:

Cardiac rhythm disorders reflect failures of impulse generation and/or conduction. With the exception of ablation methods that yield selective endocardial destruction, present therapies are nonspecific and/or palliative. Progress in understanding the underlying biology opens up prospects for new alternatives. This article reviews the present state of the art in gene- and cell-based therapies to correct cardiac rhythm disturbances. We begin with the rationale for such approaches, briefly discuss efforts to address aspects of tachyarrhythmia, and review advances in creating a biological pacemaker to cure bradyarrhythmia. Insights gained bring the field closer to a paradigm shift away from devices and drugs, and toward biologics, in the treatment of rhythm disorders.
Dissociating Linguistic and Task-related Activity in the Left Inferior Frontal Gyrus
Authors: Wright Paul , Randall Billi , Marslen-Wilson William D. , Tyler Lorraine K.
Published: March 2010

The left inferior frontal gyrus (LIFG) has long been claimed to play a key role in language function. However, there is considerable controversy as to whether regions within LIFG have specific linguistic or domain-general functions. Using fMRI, we contrasted linguistic and task-related effects by presenting simple and morphologically complex words while subjects performed a lexical decision (LD) task or passively listened (PL) without making an overt response. LIFG Brodmann's area 47 showed greater activation in LD than PL, whereas LIFG Brodmann's area 44 showed greater activation to complex compared with simple words in both tasks. These results dissociate task-driven and obligatory language processing in LIFG and suggest that PL is the paradigm of choice for probing the core aspects of the neural language system.
The Role of Synchrony and Ambiguity in Speech–Gesture Integration during Comprehension
Authors: Habets Boukje , Kita Sotaro , Shao Zeshu , Özyurek Asli , Hagoort Peter
Published: March 2010

During face-to-face communication, one does not only hear speech but also see a speaker's communicative hand movements. It has been shown that such hand gestures play an important role in communication where the two modalities influence each other's interpretation. A gesture typically temporally overlaps with coexpressive speech, but the gesture is often initiated before (but not after) the coexpressive speech. The present ERP study investigated what degree of asynchrony in the speech and gesture onsets are optimal for semantic integration of the concurrent gesture and speech. Videos of a person gesturing were combined with speech segments that were either semantically congruent or incongruent with the gesture. Although gesture and speech always overlapped in time, gesture and speech were presented with three different degrees of asynchrony. In the SOA 0 condition, the gesture onset and the speech onset were simultaneous. In the SOA 160 and 360 conditions, speech was delayed by 160 and 360 msec, respectively. ERPs time locked to speech onset showed a significant difference between semantically congruent versus incongruent gesture–speech combinations on the N400 for the SOA 0 and 160 conditions. No significant difference was found for the SOA 360 condition. These results imply that speech and gesture are integrated most efficiently when the differences in onsets do not exceed a certain time span because of the fact that iconic gestures need speech to be disambiguated in a way relevant to the speech context.
The Buddha of the North: Swedenborg and Transpacific Zen
Authors: Zuber Devin
Published: March 2010

The Scandinavian scientist-mystic Emanuel Swedenborg (1688-1772) has had a curious relationship to the history of how Western literature has responded to Buddhism. Since Honoré de Balzac’s claim in the 1830s that Swedenborg was “a Buddha of the north,” Swedenborg’s mystical teachings have been consistently aligned with Buddhism by authors on both sides of the pacific, from D. T. Suzuki to Philangi Dasa, the publisher of the first Buddhist journal in North America. This essay explores the different historical frames that allowed for this steady correlation, and argues that the rhetorical and aesthetic trope of “Swedenborg as Buddha” became a point of cultural translation, especially between Japanese Zen and twentieth-century Modernism. Swedenborg’s figuration in the earlier work of Ralph Waldo Emerson and William Blake, moreover, might begin to account for the peculiar ways those two Romantics have particularly affected modern Japanese literature. The transpacific flow of these ideas ultimately complicates the Orientalist critique that has read Western aesthetic contact with Buddhism as one of hegemonic misappropriation.
Nematicidal activity against Bursaphelenchus xylophilus of isoobtusilactone A isolated from Persea americana
Authors: Dang Quang Le , Kwon Hyeok Ran , Choi Yong Ho , Choi Gyung Ja , Jang Kyoung Soo , Park Myung Soo , Lim Chi Hwan , Ngoc Luu Hoang , Kim Jin-Cheol
Published: March 2010

Methanol extracts of 50 plant species were assessed for nematicidal activity
against the pine wood nematode (PWN), Bursaphelenchus xylophilus. Out of
these, five extracts: Justicia diclipteroides subsp. usambarica; Nerium
oleander; Persea americana; Scadoxus multiflorus subsp. multiflorus; and
Thespesia populnea, caused 96-100% mortalities of pine wood nematode at 1000
μg ml–1 for 48 h. Methanol extract of the stem bark of P. americana
(avocado) and the n-hexane layer obtained from the methanol extract by
solvent partitioning caused 100% mortality of PWN at low concentrations of
125 and 63 μg ml–1, respectively. One potent nematicidal compound was
isolated from the stem bark of P. americana and its chemical structure was
determined to be isoobtusilactone A (1) by mass and NMR spectral analyses.
The chemical showed a very strong nematicidal activity against PWN; it
caused mortalities of over 97% at concentrations higher than 50 μg ml–1.
Compared with a commercial synthetic nematicide, morantel tartrate, compound
1 showed a little more potent activity. The results suggested that compound
1 may have the potential to be explored as a natural nematicide or be useful
as a lead molecule for development of new nematicidal agents for controlling
the pine wilt disease caused by B. xylophilus.
Ultrastructure of the male reproductive system of the free-living marine nematode Paracyatholaimus pugettensis Wieser & Hopper, 1967 (Chromadorida: Cyatholaimidae)
Authors: Zograf Julia K.
Published: March 2010

Although nematodes are a well studied group of multicellular organisms, until now the only information on the cellular structure of the male reproductive system of marine nematodes is that on the histology of free-living marine nematode from the order Enoplida. The fine structure of the male reproductive system of the free-living marine nematode Paracyatholaimus pugettensis (Chromadorida: Cyatholaimidae) from the Sea of Japan has been studied using TEM. The testis epithelium has a large distal tip cell similar to that described for representatives of the subclass Rhabditia. The epithelial wall of the testis is differentiated along its length. The proximal part of the epithelial tube consists of relatively large cells bearing numerous surface outgrowths that permeate between the developing spermatocytes. The epithelium in the middle region of the testis is formed from extremely flattened cells. The distal part of the testis – the seminal vesicle – is filled with immature spermatozoa and consists of absorptive cells. The seminal vesicle is followed by the vas deferens. The gonoduct is also differentiated along its length, the first third being formed from synthetically active epithelial cells, the two layers of which form a tiled structure. There is no lumen in the gonoduct and it is probable that, due to the tiled structure, the epithelial cells move apart to create space for the spermatozoa during ejaculation. The posterior two-thirds of the duct is surrounded by muscle cells that create the necessary pressure during ejaculation. The enlarged epithelial cells of the vas deferens show vigorous synthetic activity, which is probably involved in the transformation of immature spermatozoa into mature gametes.