bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Caraway Oil Poultices in Treating Irritable Bowel Syndrome - A Randomized Controlled Cross-Over Trial
Authors: Lauche Romy , Janzen Anke , Lüdtke Rainer , Cramer Holger , Dobos Gustav , Langhorst Jost
Published: June 2015

Background/Aim: Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder, with only limited evidence regarding self-management approaches. This study tested the efficacy of caraway oil poultices (CarO) for treating IBS. Methods: This randomized controlled open-label cross-over trial included three treatment periods with hot CarO and hot olive oil poultice (OlivH) or nonheated poultices (OlivC) with olive oil as control interventions. Patients applied each intervention daily for 3 weeks. The primary outcome was symptom severity (IBS-SSS); secondary outcomes included responder rates (improvement ≥50 IBS-SSS), quality of life (EQ-5D, IBS-QOL), psychological distress (HADS), adequate relief, and safety. Results: 48 patients with IBS were included (40 females, 53.9 ± 14.4 years). A significant difference was found for symptom severity in favor of CarO compared to OlivC (difference -38.4, 95% CI -73.6, -3.1, p = 0.033), but not compared to OlivH (difference -24.3, 95% CI -56.5, 7.9, p = 0.139). Responder rates were highest for CarO compared to OlivH and OlivC (43.9, 20.0, 18.9%, respectively). Within the CarO, 51.8% reported adequate relief compared to 23.5% (OlivH) and 25.8% (OlivC). One adverse event (gastrointestinal infection) was reported during CarO. Conclusion: Hot caraway oil poultices appear effective and safe, although their effects may be a result of the heat application. Patients reported highest levels of subjective benefit from caraway oil poultices, making their use appropriate in the self-management of IBS.
Non-Celiac Gluten Sensitivity among Patients Perceiving Gluten-Related Symptoms
Authors: Capannolo Annalisa , Viscido Angelo , Barkad Mohamed Ali , Valerii Giorgio , Ciccone Fabiana , Melideo Dina , Frieri Giuseppe , Latella Giovanni
Published: June 2015

Background: Non-celiac gluten sensitivity (NCGS) is a recently recognized disorder, characterized by the occurrence of symptoms following gluten ingestion. It is often self-diagnosed by the patient, but should be confirmed by the response to a gluten-free diet, followed by a gluten challenge. Celiac disease (CD) and wheat allergy (WA) must first be ruled out. Aims: (1) to determine the frequency of visits performed for symptoms self-perceived as gluten-related; (2) to assess in this cohort, the proportion of patients satisfying the diagnostic criteria for NCGS. Methods: A two-year prospective study including all consecutive patients complaining of gluten-related symptoms. NCGS was diagnosed on the basis of the disappearance of the symptoms within 6 months of a gluten-free diet, followed by their reappearance with the reintroduction of gluten in the diet for 1 month. Results: Three hundred and ninety two patients complaining of gluten-related symptoms were enrolled; 26 of these (6.63%) were affected by CD, 2 (0.51%) by WA and 27 were diagnosed with NCGS (6.88%). The remaining 337 patients (85.96%) did not experience any change of symptoms with a gluten-free diet. The PPV of the gluten-related symptom was found to be 7%. Conclusion: Eighty six percent of patients reporting gluten-related symptoms have neither NCGS, nor CD, nor WA. Self-perceived gluten-related symptoms are rarely indicative of the presence of NCGS.
Remission Time after Rituximab Treatment for Autoimmune Bullous Disease: A Proposed Update Definition
Authors: Iranzo Pilar , Pigem Ramon , Giavedoni Priscila , Alsina-Gibert Mercè
Published: June 2015

A therapeutic endpoint is a very important tool to evaluate response in clinical trials. In 2005, a consensus statement identified two late endpoints of disease activity in pemphigus: complete remission off therapy and complete remission on therapy, both definitions applying to patients without lesions for at least 2 months. The same period of time was considered for partial remission off/on therapy. These definitions were later applied to bullous pemphigoid and are considered in most studies on autoimmune bullous disease. These endpoints were established for different adjuvant agents, but at that moment, rituximab was not considered. Rituximab is known for the long duration of its effect, and in most studies relapses have been reported later than 6 months after treatment. In our opinion, time to remission after rituximab treatment should be redefined.
Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma
Authors: Li Chen , Chen Jing , Zhang Kai , Feng Bing , Wang Rui , Chen Longbang
Published: June 2015

Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.
The Bacterial Component Flagellin Induces Anti-Sepsis Protection Through TLR-5, IL-1RN and VCAN During Polymicrobial Sepsis in Mice
Authors: Zhu Jiang , Duan Guangjie , Lang Lang , Liu Yao , Zhu Junmin , Wang Hu , Liu Yousheng
Published: June 2015

Background: The present study was designed to observe the effects of the bacterial component flagellin on anti-sepsis protection through TLR-5, VCAN and IL-1RN. Methods: A clinically relevant model of sepsis was induced by cecal ligation and puncture (CLP). An in vitro culture of endothelial cells was analyzed. Results: Flagellin induced anti-sepsis protection through inhibition of inflammation and induction of endothelial proliferation by down-regulating the expression of TLR 3, TLR 4, and IL-1RN and promoting the expression of VCAN in mice 24 h post-CLP. In vitro, flagellin promoted the proliferation of endothelial cells. These effects could be inhibited by transfection of endothelial cells with VCAN siRNA or IL-1RN over-expression constructs. VCAN expression decreased after transfection of the cells with an IL-1RN over-expression construct and increased after transfection of the cells with an IL-1RN siRNA construct. IL-1RN expression remained unchanged after transfection of the cells with VCAN over-expression or siRNA constructs. Conclusions: These data suggest that flagellin pretreatment promoted anti-sepsis protection through the TLR-5, IL-1RN and VCAN pathway. This pathway is necessary to mediate endothelial repair and thereby promote survival following sepsis challenge.
MMP13 Regulates Aggressiveness of Pediatric Multiple Myeloma Through VEGF-C
Authors: Xu Lingyun , Sun Kai , Xia Min , Li Xiaoli , Lu Yanming
Published: June 2015

Background/Aims: Even though the blood and lymphatic vascular systems are both involved in the occurrence of cancer metastases, it is believed that lymphatic system is primarily responsible for the initial metastasis. Nevertheless, the molecular mechanisms underlying lymphangiogenesis of multiple myeloma (MM), especially in pediatric period, have not been clarified. Methods: Here we studied vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 13 (MMP13) in pediatric MM patients. We overexpressed or inhibited VEGF-C in MM cells to study their effects on MMP13, and vice versa. A specific inhibitor for PI3k/Akt signaling pathway was used to examine the role of PI3k/Akt signaling in this regulatory axis. Results: Both VEGF-C and MMP13 significantly upregulated in MM with lymph-node metastases. A strong correlation between VEGF-C and MMP13 were detected in MM specimen. Using a human MM line 8226, we found that VEGF-C was regulated by MMP13 in MM cells, but not vice versa. Moreover, a specific PI3k/Akt inhibitor significantly abolished the effect of MMP13 on VEGF-C activation. Conclusion: Since VEGF-C is a well-known growth factor for lymphatic vessels, our data suggest that MMP13 may activate VEGF-C to promote cancer cell metastasis through lymphatic vascular systems in pediatric MM.
Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway
Authors: Liu Xiangzhou , Chen Wan , Zhou You , Tang Kanglai , Zhang Jiqiang
Published: June 2015

Background/Aims: Tendinopathy is a common sports injury that is manifested by the heterotopic ossification of tendon tissue. Tendon stem cells (TSCs) are prone to osteogenic differentiation under excessive tension. The underlying mechanisms remain poorly understood. Methods: Uniaxial mechanical tension (UMT) served to stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz; 48, 60, or 72 hours). Results: The osteogenic differentiation of rTDSCs appeared after UMT along with increased mRNA expression of the osteogenic genes Runx2, Dlx5, Alpl, and Col1a1 and increased Runx2 protein expression. Wnt5a, Wnt5b and P-JNK protein levels were also upregulated after UMT stimulation. The inhibition of JNK expression by SP600125 and JNK1-shRNA decreased UMT-induced Runx2 protein expression, and the activation of JNK expression by anisomycin and JNK1-cDNA increased UMT-induced Runx2 protein expression. When shRNA knocked down Wnt5a and Wnt5b expression in rTDSCs, the induction of Runx2 and P-JNK expression by UMT was reduced. The inhibition of Runx2 expression could be rescued by the activation of JNK expression by anisomycin. Conclusion: UMT induced the osteogenic differentiation of rTDSCs via the Wnt5a/Wnt5b/JNK signaling pathway. Accordingly, this pathway may influence the heterotopic ossification of tendon tissue subjected to excessive tension.
Fasudil Stimulates Neurite Outgrowth and Promotes Differentiation in C17.2 Neural Stem Cells by Modulating Notch Signalling but not Autophagy
Authors: Chen Shu , Luo Ming , Zhao Yuming , Zhang Yimin , He Mingliang , Cai Wangqing , Liu Anmin
Published: June 2015

Background: Neurite outgrowth is one of the important therapeutic strategies for neuronal plasticity and regeneration in neural disorders. Fasudil is a clinical medication that is used to treat subarachnoid haemorrhage (SAH) and that is beneficial for many animal models of central nervous system (CNS) diseases. In this study, we hypothesised that fasudil administration would promote neurite outgrowth in neural stem cells (NSCs). Methods: Changes in cell morphology were imaged under a light microscope, and neurite-bearing cells were counted. Cell viability and the necrosis rate were determined by MTT and LDH assays, respectively. Additionally, western blot and immunofluorescence analyses were performed to detect protein expression levels. Results: We found that fasudil promoted neurite outgrowth in C17.2 cells in a time- and dose-dependent manner. The neurite-bearing C17.2 cells were differentiated by detecting the changes in neural and astrocytic markers after fasudil treatment through down-regulating Notch signalling. Previously, fasudil was reported to induce autophagy, which plays an important role in neural differentiation. However, both rapamycin, an autophagy inducer, and 3-methyl-adenine (3-MA), an autophagy inhibitor, had no effects on the fasudil-induced neurite outgrowth, suggesting that autophagy may be not involved in this process. Conclusion: In summary, fasudil could stimulate neurite outgrowth and differentiation in C17.2 cells by modulating Notch signalling but not autophagy.
Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia
Authors: Shi Zhonghua , Zhao Chun , Long Wei , Ding Hongjuan , Shen Rong
Published: June 2015

Background: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Method: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. Result: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Conclusions: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology.
The Role of Janus Kinase 3 in the Regulation of Na+/K+ ATPase under Energy Depletion
Authors: Hosseinzadeh Zohreh , Honisch Sabina , Schmid Evi , Jilani Kashif , Szteyn Kalina , Bhavsar Shefalee , Singh Yogesh , Palmada Monica , Umbach Anja T. , Shumilina Ekaterina , Lang Florian
Published: June 2015

Background/Aims: Janus kinase-3 (JAK3) is activated during energy depletion. Energy-consuming pumps include the Na+/K+-ATPase. The present study explored whether JAK3 regulates Na+/K+-ATPase in dendritic cells (DCs). Methods: Ouabain (100 µM)-sensitive (Iouabain) and K+-induced (Ipump) outward currents were determined by utilizing whole cell patch-clamp, Na+/K+-ATPase α1-subunit mRNA levels by RT-PCR, Na+/K+-ATPase protein abundance by flow cytometry or immunofluorescence, and cellular ATP by luciferase-assay in DCs from bone marrow of JAK3-knockout (jak3-/-) or wild-type mice (jak3+/+). Ipump was further determined by voltage clamp in Xenopus oocytes expressing JAK3, active A568VJAK3 or inactive K851AJAK3. Results: Na+/K+-ATPase α1-subunit mRNA and protein levels, as well as Ipump and Iouabain were significantly higher in jak3-/-DCs than in jak3+/+DCs. Energy depletion by 4h pre-treatment with 2,4-dinitro-phenol significantly decreased Ipump in jak3+/+ DCs but not in jak3-/-DCs. Cellular ATP was significantly lower in jak3-/-DCs than in jak3+/+DCs and decreased in both genotypes by 2,4-dinitro-phenol, an effect significantly more pronounced in jak3-/-DCs than in jak3+/+DCs and strongly blunted by ouabain in both jak3+/+ and jak3-/-DCs. Ipump and Iouabain in oocytes were decreased by expression of JAK3 and of A568VJAK3 but not of K851AJAK3. JAK3 inhibitor WHI-P154 (4-[(3'-bromo-4'-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 22 μM) enhanced Ipump and Iouabain in JAK3 expressing oocytes. The difference between A568VJAK3 and K851AJAK3 expressing oocytes was virtually abrogated by actinomycin D (50 nM). Conclusions: JAK3 down-regulates Na+/K+-ATPase activity, an effect involving gene expression and profoundly curtailing ATP consumption.
Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts
Authors: Wu Hong-Jin , Yang Ji-Yuan , Jin Min , Wang Sheng-Qi , Wu De-Lin , Liu Yu-Na , Yan Xu , Yang Cui , Zhang Ge , He Jing
Published: June 2015

Background/Aims: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid (GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. Materials and Methods: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). Results: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. Conclusion: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.
Nexrutine Inhibits Cancer Cell Growth as a Consequence of Mitochondrial Damage and Mitophagy
Authors: Wu Xiang , Zhou Shao-ming , Ding Yi-Ling , Gong Ying-ping , Zeng Weiqi , Cui Yi
Published: June 2015

Background/Aims: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. Methods: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. Results: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. Conclusion: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.
Enhanced Suicidal Erythrocyte Death Contributing to Anemia in the Elderly
Authors: Lupescu Adrian , Bissinger Rosi , Goebel Tobias , Salker Madhuri S. , Alzoubi Kousi , Liu Guilai , Chirigiu Liviu , Mack Andreas F. , Qadri Syed M. , Lang Florian
Published: June 2015

Background/Aims: Anemia, a common condition in the elderly, could result from impaired formation and/or from accelerated loss of circulating erythrocytes. The latter could result from premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca2+-concentration ([Ca2+]i), oxidative stress and ceramide. The present study explored whether eryptosis is altered in elderly individuals and, if so, to identify underlying mechanisms. Methods: Blood was drawn from healthy young (n=11, age 31.3±1.7 years) and elderly (n=16, age 88.6±0.9 years) individuals. PS exposure was estimated from annexin V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from 2',7'dichlorodihydrofluorescein fluorescence, reduced glutathione (GSH) from mercury orange fluorescence and ceramide from FITC-conjugated antibody binding in flow cytometry. Measurements were made in erythrocytes from freshly drawn blood and in erythrocytes exposed in vitro for 24 h to plasma from young or elderly individuals. Results: Elderly individuals suffered from severe anemia (hemoglobin 10.5±0.3 g/100 ml) despite enhanced number of reticulocytes (2.3±0.2%). The percentage of PS-exposing erythrocytes was significantly higher in the elderly (2.5±0.2%) than in the young volunteers (1.3±0.1%). The increase in PS exposure was paralleled by significant increase of ROS and significantly decreased levels of reduced GSH. Erythrocyte [Ca2+]i, and ceramide abundance tended to be higher in the elderly, differences, however, not reaching statistical significance. Conclusions: The anemia of elderly individuals is mainly if not exclusively due to enhanced eryptosis, resulting at least in part from GSH deficiency and increased oxidative stress.
Ascorbic Acid-Induced Cardiac Differentiation of Murine Pluripotent Stem Cells: Transcriptional Profiling and Effect of a Small Molecule Synergist of Wnt/β-Catenin Signaling Pathway
Authors: Ivanyuk Dina , Budash Galina , Zheng Yunjie , Gaspar John Antony , Chaudhari Umesh , Fatima Azra , Bahmanpour Soghra , Grin Vladislav K. , Popandopulo Andrey G. , Sachinidis Agapios , Hescheler Jürgen , Šarić Tomo
Published: June 2015

Background: Reproducible and efficient differentiation of pluripotent stem cells (PSCs) to cardiomyocytes (CMs) is essential for their use in regenerative medicine, drug testing and disease modeling. The aim of this study was to evaluate the effect of some previously reported cardiogenic substances on cardiac differentiation of mouse PSCs. Methods: Differentiation was performed by embryoid body (EB)-based method using three different murine PSC lines. The differentiation efficiency was monitored by RT-qPCR, immunocytochemistry and flow cytometry, and the effect mechanistically evaluated by transcriptome analysis of treated EBs. Results: Among the five tested compounds (ascorbic acid, dorsomorphin, cyclic adenosine 3',5'-monophosphate, cardiogenol C, cyclosporin A) only ascorbic acid (AA) exerted a strong and reproducible cardiogenic effect in CGR8 cells which was less consistent in other two PSC lines. AA induced only minor changes in transcriptome of CGR8 cells after administration during the initial two days of differentiation. Cardiospecific genes and transcripts involved in angiogenesis, erythropoiesis and hematopoiesis were up-regulated on day 5 but not on days 2 or 3 of differentiation. The cardiac differentiation efficiency was improved when QS11, a small-molecule synergist of Wnt/β-catenin signaling pathway, was added to cultures after AA-treatment. Conclusion: This study demonstrates that only minor transcriptional changes are sufficient for enhancement of cardiogenesis of murine PSCs by AA and that AA and QS11 exhibit synergistic effects and enhance the efficiency of CM differentiation of murine PSCs.
Cardiomyocyte-Specific Transgenic Expression of Prolyl-4-Hydroxylase Domain 3 Impairs the Myocardial Response to Ischemia
Authors: Zieseniss Anke , Hesse Amke R. , Jatho Aline , Krull Sabine , Hölscher Marion , Vogel Sabine , Katschinski Dörthe M.
Published: June 2015

Aims: The prolyl-4-hydroxylase domain (PHD) enzymes are representing novel therapeutic targets for ischemic tissue protection. Whereas the consequences of a knock out of the PHDs have been analyzed in the context of cardioprotection, the implications of PHD overexpression is unknown so far. Methods and Results: We generated cardiomyocyte-specific PHD3transgenic mice (cPhd3tg). Resting cPhd3tg mice did not show constitutive accumulation of HIF-1α or HIF-2α or changes in HIF target gene expression in the heart. Cardiac function was followed up for 14 months in these mice and found to be unchanged. After challenging the cPhd3tg mice with ligation of the left anterior descending artery, HIF-1α/-2α accumulation in the left ventricles was blunted. This was associated with a significantly increased infarct size of the cPhd3tg compared to wild type mice. Conclusion: Whereas overexpression of PHD3 in the resting state does not significantly influence cardiac function, it is crucial for the cardiac response to ischemia by affecting HIFα accumulation in the ischemic tissue.
Antagonism Between Saturated and Unsaturated Fatty Acids in ROS Mediated Lipotoxicity in Rat Insulin-Producing Cells
Authors: Gehrmann Wiebke , Würdemann Wiebke , Plötz Thomas , Jörns Anne , Lenzen Sigurd , Elsner Matthias
Published: June 2015

Background/Aims: Elevated levels of non-esterified fatty acids (NEFAs) are under suspicion to mediate β-cell dysfunction and β-cell loss in type 2 diabetes, a phenomenon known as lipotoxicity. Whereas saturated fatty acids show a strong cytotoxic effect upon insulin-producing cells, unsaturated fatty acids are not toxic and can even prevent toxicity. Experimental evidence suggests that oxidative stress mediates lipotoxicity and there is evidence that the subcellular site of ROS formation is the peroxisome. However, the interaction between unsaturated and saturated NEFAs in this process is unclear. Methods: Toxicity of rat insulin-producing cells after NEFA incubation was measured by MTT and caspase assays. NEFA induced H2O2 formation was quantified by organelle specific expression of the H2O2 specific fluorescence sensor protein HyPer. Results: The saturated NEFA palmitic acid had a significant toxic effect on the viability of rat insulin-producing cells. Unsaturated NEFAs with carbon chain lengths >14 showed, irrespective of the number of double bonds, a pronounced protection against palmitic acid induced toxicity. Palmitic acid induced H2O2 formation in the peroxisomes of insulin-producing cells. Oleic acid incubation led to lipid droplet formation, but in contrast to palmitic acid induced neither an ER stress response nor peroxisomal H2O2 generation. Furthermore, oleic acid prevented palmitic acid induced H2O2 production in the peroxisomes. Conclusion: Thus unsaturated NEFAs prevent deleterious hydrogen peroxide generation during peroxisomal β-oxidation of long-chain saturated NEFAs in rat insulin-producing cells.
Thalamic and Cerebellar Gray Matter Volume Reduction in Synthetic Cannabinoids Users
Authors: Nurmedov Serdar , Metin Baris , Ekmen Sehadet , Noyan Onur , Yilmaz Onat , Darcin Asli , Dilbaz Nesrin
Published: June 2015

Background: Synthetic cannabinoids are compounds that bind cannabinoid receptors with a high potency and have been used widely in Europe by young people. However, little is known about the pharmacology and morphological effects of this group of substances in the brain. This study is aimed at investigating the morphological differences among synthetic cannabinoids users and healthy controls. Methods: Voxel-based morphometry was used to investigate the differences in brain tissue composition in 20 patients with synthetic cannabinoids use and 20 healthy controls. All participants were male. Results: Compared to healthy controls, voxel of interest analyses showed that regional grey matter volume in both left and right thalamus and left cerebellum was significantly reduced in synthetic cannabinoids users (p < 0.05). No correlation has been found between the age of first cannabis use, duration of use, frequency of use and grey matter volume. Discussion: These preliminary results suggest an evidence of some structural differences in the brain of synthetic cannabinoids users, and point the need for further investigation of morphological effects of synthetic cannabinoids in the brain.
Infection with Rhinovirus Facilitates Allergen Penetration Across a Respiratory Epithelial Cell Layer
Authors: Gangl Katharina , Waltl Eva E. , Vetr Helga , Cabauatan Clarissa R. , Niespodziana Katarzyna , Valenta Rudolf , Niederberger Verena
Published: June 2015

Background: Rhinovirus infections are a major risk factor for asthma exacerbations. We sought to investigate in an in vitro system whether infection with human rhinovirus reduces the integrity and barrier function of a respiratory epithelial cell layer and thus may influence allergen penetration. Methods: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of respiratory epithelium. The cell monolayer was infected with human rhinovirus 14 at 2 different doses. The extent and effects of transepithelial allergen penetration were assessed using transepithelial resistance measurements and a panel of 125I-labeled purified recombinant respiratory allergens (rBet v 1, rBet v 2, and rPhl p 5). Results: Infection of respiratory cell monolayers with human rhinovirus decreased transepithelial resistance and induced a pronounced increase in allergen penetration. Conclusions: Our results indicate that infection with rhinovirus damages the respiratory epithelial barrier and allows allergens to penetrate more efficiently into the subepithelial tissues where they may cause increased allergic inflammation.
Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice
Authors: Chang Lisa M. , Song Ying , Li Xiu-Min , Sampson Hugh A. , Masilamani Madhan
Published: June 2015

Background: Food allergy research is hampered by a lack of animal models that consistently mimic human food allergic responses. Laboratory mice are generally fed grain-based chow made with large amounts of soybeans rich in immunomodulatory isoflavones. We tested the role of dietary soy components in the induction of food allergic responses in the BALB/c mouse strain, which is known to be resistant to anaphylaxis when orally challenged by food allergens. Methods: Mice were fed a soy-free diet for 2 generations. After weaning, mice were maintained on the same diet or fed a diet containing soy isoflavones, i.e. genistein and daidzein, followed by weekly oral sensitizations with crude peanut extract plus cholera toxin and finally challenged at week 7. The anaphylactic symptoms, body temperature, peanut-specific antibodies and mast cell degranulation were assessed. Results: Soy-free diet mice showed significantly higher anaphylactic symptom scores and mast cell degranulation after challenge and higher peanut-specific antibody levels than mice fed regular chow. Introduction of a regular soy diet or an isoflavone diet to soy-free diet mice significantly suppressed the allergic reactions compared to the soy-free diet. Conclusion: Rodent diet is an important variable and needs to be taken into consideration when designing experiments involving animal models. Our results indicate that elimination of soy components from the diet enhances peanut sensitization in BALB/c mice. In addition to serving as a valuable tool to mimic human food allergy, the dietary influence on the immune response could have far-reaching consequences in research involving animal models.
Psychotherapy and Mental Health as a Psychological Science Discipline
Authors: Wittchen Hans-Ulrich , Härtling Samia , Hoyer Jürgen
Published: June 2015

The psychological sciences offer a large spectrum of theories, principles, and methodological approaches to understand mental health, normal and abnormal functions and behaviours, as well as mental disorders. Based on continued research progress, psychology has derived a wide range of effective interventions for behaviour change and the prevention, treatment and rehabilitation of mental disorders. Thus, psychology and clinical psychology in particular should be regarded as the ‘mother' science for psychotherapy and psychotherapeutic practice. This paper provides a selective overview of the scope, strengths and gaps in psychological research to depict the advances needed to inform future research agendas on mental disorders and psychological interventions in the context of psychotherapy. Most maladaptive health behaviours and mental disorders can be conceptualised as the result of developmental dysfunctions of psychological functions and processes, and as associated neurobiological and genetic processes in interaction with behaviour and the environment. An integrative translational model, linking basic and experimental research with clinical research and population-based prospective-longitudinal studies is proposed for improving identification of critical core vulnerability and risk factors and core pathogenic mechanisms. The proposed framework is expected to allow a more stringent delineation of targeted preventive and therapeutic psychological interventions and an optimisation and better understanding of cognitive-behavioural therapies and other psychological interventions. Based on a European consultation process, a ‘Science of Behaviour Change' programme with the promise of improved diagnosis, treatment and prevention of both health-risk behaviour constellations and mental disorders is proposed.
Unusual Case of Cerebral Venous Thrombosis in Patient with Crohn's Disease
Authors: Kim Inha , Min Kyung-Hyun , Yeo Minju , Kim Ji Seon , Lee Sung Hyun , Lee Sang Soo , Shin Kyeong Seob , Youn Sei Jin , Shin Dong Ick
Published: June 2015

The development of cerebral venous thrombosis (CVT) as a secondary complication of Crohn's disease (CD) seems to be rare, but it is generally accepted that the disease activity of CD contributes to the establishment of a hypercoagulable state. Here, we describe a case of CVT that developed outside the active phase of CD. A 17-year-old male visited the emergency room because of a sudden onset of right-sided weakness and right-sided hypesthesia. He had been diagnosed with CD 1 year before and was on a maintenance regimen of mesalazine and azathioprine. He did not exhibit any symptoms indicating a CD flare-up (bloody stools, abdominal pain, complications, or weight loss). A brain MRI scan revealed an acute infarction of the left frontal cortex and a cortical subarachnoid hemorrhage. Additionally, a magnetic resonance venography revealed a segmental filling defect in the superior sagittal sinus and also the non-visualizability of some bilateral cortical veins. The characteristics of the present case suggest that the risk of CVT is most likely related to CD per se rather than disease activity associated with CD.
Lost in Translation: Psychologische Mechanismen und Psychotherapie
Authors: Flor Herta
Published: June 2015

In diesem Artikel möchte ich zu den folgenden Punkten Stellung nehmen: 1. Psychische Störungen basieren auf psychologischen Mechanismen und müssen aus diesen heraus verstanden werden 2. Psychische Störungen sind keine Hirnerkrankungen - jedoch kann das Verständnis psychischer Störungen durch die Kenntnis biologischer Prozesse verbessert werden. 3. Psychotherapie muss an diesen Mechanismen ansetzen und sollte von einer störungsorientierten zu einer mechanismenorientierten Therapie kommen. 4. Dies setzt eine mechanismenorientierte Diagnostik voraus. Der RDoc-Ansatz ist ein wichtiger Versuch, aber er greift zu kurz, was die psychologischen Mechanismen betrifft. 5. Pharmakotherapie und andere somatische Therapien können Psychotherapie unterstützen, wenn sie zur Veränderung der psychologischen Mechanismen eingesetzt werden. 6. Psychotherapie kann auch bei organischen Erkrankungen wirksam eingesetzt werden. 7. Wir sind noch weit davon entfernt, die Erkenntnisse der Grundlagenforschung in der Psychologie und den Neurowissenschaften in die Konstruktion neuer Psychotherapien einzubauen. Dafür brauchen wir bessere Förderinstrumente als die bislang zur Verfügung stehenden und eine politische und finanzielle Priorität für die Therapieforschung.
Outcome Predictors of Acute Stroke Patients in Need of Intensive Care Treatment
Authors: Alonso Angelika , Ebert Anne D. , Kern Rolf , Rapp Simone , Hennerici Michael G. , Fatar Marc
Published: June 2015

Background: The prognosis of stroke patients admitted to intensive care units (ICU) is commonly regarded to be poor. However, only limited data regarding outcome predictors are available. Patients and Methods: Out of 4,958 consecutive patients admitted to our stroke unit with the diagnosis of acute stroke, after analysis we identified 347 patients (164 male) in need of ICU management. In-hospital and post-rehabilitation mortality as well as functional outcome at discharge and after rehabilitation were analyzed. Results: Ischemic stroke was diagnosed in 252 patients (72.6%) and intracerebral hemorrhage occurred in 95 patients (27.4%). The mean age in our cohort was considerably high (70.8 years). One hundred patients were comatose at admission. The median NIHSS score at admission in the remaining patients was 12. Apart from stroke-related disturbances of consciousness (47.1%), the most common reasons for ICU treatment were cardiac (23.4%) and respiratory (12.1%) complications or interventional procedures requiring mechanical ventilation (11%). In all, 231/347 patients (66.6%) were mechanically ventilated (mean 84 h). In-hospital mortality (143/347; 41.2%) was associated with old age, poor NIHSS score at admission, intracerebral hemorrhage and mechanical ventilation (p < 0.001 in all). Further, admission to ICU because of stroke-related impairment of consciousness increased in-hospital mortality (p < 0.001). Similarly, poor outcome after rehabilitation was associated with old age (p = 0.029) and mechanical ventilation (p < 0.001). In patients ≥80 years with either intracerebral hemorrhage or need of mechanical ventilation, outcome was unfavorable in nearly any case. However, the overall post-rehabilitation outcome did not differ between patients with intracerebral hemorrhage and ischemic stroke (p = 0.275). Conclusion: The stroke population in our study was associated with an increased early mortality; however, given the same conditions, it was old with a high percentage of patients requiring mechanical ventilation. This did not result in increased in-hospital mortality rates compared to younger and less severely affected cohorts. Thus, ICU management is a life-saving initiative even among the elderly. However, the functional outcome was poor in older patients, thus limiting the benefits of ICU care in these patients.
Pyramidal Lobe of the Thyroid: Anatomical Considerations of Importance in Thyroid Cancer Surgery
Authors: Sinos George , Sakorafas George H.
Published: June 2015

The pyramidal lobe is a remnant of the thyroglossal duct and is considered a normal component of the thyroid gland. The pyramidal lobe may be affected by the diseases that affect the rest of the thyroid parenchyma. A practicing endocrine surgeon should keep the anatomical variations of the pyramidal lobe in mind to achieve a completely total thyroidectomy, when indicated. This approach is especially important in thyroid cancer surgery, given the high incidence of multifocality of papillary thyroid cancer, the increased effectiveness of adjuvant radioiodine therapy following a really total thyroidectomy, and the increased sensitivity of serum thyroglobulin measurements during the follow-up of these patients.
Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma
Authors: Chhabra Akansha , Mukherjee Vikramjit , Chowdhary Mudit , Danckers Mauricio , Fridman David
Published: June 2015

Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis.
A 15-Year Nationwide Epidemiological Analysis of Guillain-Barré Syndrome in Taiwan
Authors: Huang Wan-Chun , Lu Chin-Li , Chen Solomon Chih-Cheng
Published: June 2015

Background: Guillain-Barré syndrome (GBS) is a potentially life-threatening disease that typically occurs after a preceding infectious disease. An accurate estimation of GBS incidence would be useful for investigating the potential causal relationships between risk factors and GBS. Here we described the nationwide incidence of GBS in Taiwan. Methods: The cases of GBS were obtained from all admission records of the National Health Insurance Research Database. We identified all of the first-admitted GBS patients by a code of ICD-9-CM 357.0 presented at the discharge diagnoses in admission records between 1997 and 2011. Calendar year, age, and sex-specific incidence, and seasonal variation were estimated. Results: A total of 5,998 patients were identified. The male-to-female rate ratio was 1.54. The crude incidence rate was 1.65 per 100,000 person-years. The incidence of GBS was lowest in people aged less than 20 and increased with age, especially in people older than 50 years. In spring, the incidence was 10% higher than in other seasons. Conclusions: The overall incidence is in line with previous large-scale studies. A significant higher rate in spring is also shown. The potential reasons for the seasonality and higher incidence among older patients should be further investigated.
A Case of Intestinal Mastocytosis Misdiagnosed as Crohn's Disease
Authors: Reggiani Stefania , Cosso Loretta , Adriani Alessandro , Pantaleoni Stefano , Risso Alessandro , Vittone Federico , Chiusa Luigi , Sapone Nicoletta , Astegiano Marco
Published: June 2015

Systemic mastocytosis (SM) is a rare, heterogeneous and progressive disease, characterized by the accumulation of atypical mast cells in various organs, including the gastrointestinal tract. Gastrointestinal symptoms are present in up to 80% of patients with SM, the most common being abdominal pain, diarrhea, nausea and vomiting. Up to 50% of patients with SM do not have classical skin lesions at presentation, and in these patients the diagnosis of SM can be difficult for years. Here we report a case of SM that initially mimicked inflammatory bowel disease, although the patient showed poor response to steroid therapy. The right diagnosis was made only on the surgical specimen obtained after emergency surgery for intestinal obstruction. SM should therefore be considered in the diagnostic approach in patients with gastrointestinal symptoms not attributable to other pathologies and in cases of suspected inflammatory bowel disease with unusual course.
A Rare Silent Killer: Right Atrial Metastasis of Thyroid Hürthle Cell Carcinoma
Authors: Luo Hongxiu , Tulpule Sunil , Alam Mahmood , Patel Reema , Sen Shuvendu , Yousif Abdalla
Published: June 2015

Hürthle cell carcinoma (HCC) is a variant of a follicular carcinoma with a tendency to higher frequency of metastases and a lower survival rate. However, intracavitary cardiac metastases from thyroid HCC are extremely rare. We describe the case of a 57-year-old female with thyroid HCC, 5 years after total thyroidectomy, who presented with dyspnea associated with hypoxia and hypotension. The computed tomography angiogram showed extensive pulmonary embolism and a 6-cm right atrial mass while the lower-extremity deep vein thrombosis studies were negative. This patient received a cardiac thrombectomy using cardiopulmonary bypass support. However, intraoperatively, we found out that the mass was from the mediastinum, directly extending into the heart and clearly unresectable since it effaced at least 1/3 of the right atrial wall. The core biopsy of the mass confirmed that it was metastatic poorly differentiated HCC of thyroidal origin. The patient eventually died of respiratory failure due to a massive pulmonary embolism. For cancer patients with unexplained dyspnea, cardiac metastases should be considered regardless of anticoagulation prophylaxis, especially when there is no deep vein thrombosis in the lower limbs. Early recognition of intracavitary cardiac metastases may help in providing prompt treatment and improving the prognosis.
Regulatory Roles of Endogenous Mitogen-Activated Protein Kinases and Tyrosine Kinases in the Pacemaker Activity of Colonic Interstitial Cells of Cajal
Authors: Shin Dong Hoon , Lee Mi Jeong , Jiao Han Yi , Choi Seok , Kim Man Woo , Park Chan Guk , Na Jisun , Kim Seok Won , Park Il Koo , So Insuk , Jun Jae Yeoul
Published: June 2015

Background and Purpose: Mitogen-activated protein (MAP) and tyrosine kinases play an important role in regulating smooth muscle contraction of the gastrointestinal (GI) tract. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate GI smooth muscle activity. Thus, the role of MAP and tyrosine kinases on the pacemaker potentials of colonic ICCs was investigated. Methods: Cultured ICCs were prepared from mice colons, and their pacemaker potentials were recorded using whole-cell patch clamping. Results: In current-clamping mode, colonic ICCs displayed spontaneous pacemaker potentials. SB203580 (a p38 MAP kinase inhibitor), SP600125 (a c-jun NH2-terminal kinase (JNK) inhibitor), genistein and herbimycin A (tyrosine kinase inhibitors) blocked the generation of pacemaker potentials. However, PD98059 (a p42/44 MAP kinase inhibitor) had no effects on pacemaker potentials. LY-294002 (phosphoinositide 3-kinase inhibitor) also reduced the pacemaker potential frequency but calphostin C and chelerythrine (protein kinase C inhibitors) had no effects. However, PD98059, SB203589, SP600125, genistein, herbimycin A, LY-294002, and calphostin C had no effect on normal pacemaker activity in small intestinal ICCs. Conclusions: Endogenous p38 MAP kinases, JNKs, tyrosine kinases, and PI3-kinases participate in the generation of pacemaker potentials in colonic ICCs but not in ICCs of the small intestine.