bluuebunny/crossref_metadata_2025 huggingface dataset:
Funicular Myelosis in a Butcher: It Was the Cream Cans
Authors: Wolpert Fabian , Baráth Krisztina , Brakowski Janis , Renzel Roland , Linnebank Michael , Gantenbein Andreas R.
Published: January 2015

Background. Funicular myelosis is a known consequence of exposure to nitrous oxide. Nevertheless, there are only a few clinical trials assessing its long-term effects and there is no literature about the role of nutritional vitamin B12 supplementation in the context of nitrous oxide abuse.Case Descriptions. We diagnosed funicular myelosis in a young butcher, who consumed high amounts of meat regularly. Since the diagnostic process did not reveal any metabolic causes, reinterrogation of the patient uncovered recreational abuse of nitrous oxide out of whipped cream can gas cartridges. After stopping abuse and supplementation of vitamin B12, the patient recovered almost completely.Conclusions. In our case, even high nutritional vitamin B12 uptake could not compensate the noxious effects of nitrous oxide. Since there are emerging reports of increasing misuse, this should be considered in the diagnostic and therapeutic care of patients with nitrous oxide abuse. Furthermore, our case emphasizes that patients with vitamin B12 deficiency should be assessed for nitrous oxide abuse.
The Prognostic Value of Intermedin in Patients with Breast Cancer
Authors: Lu Yi-Min , Zhong Jian-Bo , Wang Hai-Yong , Yu Xiong-Fei , Li Zhong-Qi
Published: January 2015

This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects usingt-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer.
Natural Frequency Analysis of Two Nonlinear Panels Coupled with a Cavity Using the Approximate Elliptic Integral Solution and the Method of Harmonic Residual Minimization
Authors: Lee Y. Y.
Published: January 2015

The nonlinear structural acoustic problem considered in this study is the nonlinear natural frequency analysis of flexible double panels using the elliptic integral solution method. There are very limited studies for this nonlinear structural-acoustic problem, although many nonlinear plate or linear double panel problems have been tackled and solved. A multistructural/acoustic modal formulation is derived from two coupled partial differential equations which represent the large amplitude structural vibrations of the flexible panels and acoustic pressure induced within the air gap. One is the von Karman’s plate equation and the other is the homogeneous wave equation. The results obtained from the proposed method approach are verified with those from a numerical method. The effects of vibration amplitude, gap width, aspect ratio, the numbers of acoustic modes and harmonic terms, and so forth on the resonant frequencies of the in-phase and out of phase modes are examined.
Improvement of the Survival of Human Autologous Fat Transplantation by Adipose‐Derived Stem‐Cells‐Assisted Lipotransfer Combined with bFGF
Authors: Jiang Aimei , Li Ming , Duan Wenjing , Dong Yilong , Wang Yanmei
Published: January 2015

Adipose‐derived stem cells (ASCs) transplanted along with autologous adipose tissue may improve fat graft survival; however, the efficacy of ASCs has been diluted by low vascularization. This study was designed to test the hypothesis that basic fibroblast growth factor (bFGF) may improve the effects of ASCs because it owns the property to boost angiogenesis. In the present study, human fat tissues were mixed with ASCs, ASCs plus 100 U bFGF, or medium as the control and then injected subcutaneously into immunologically compromised nude mice for 12 weeks. Our findings demonstrated that mixture with the ASCs significantly increased the weight and volume of the fat grafts compared to control grafts, and histological analysis revealed that both ASCs and ASCs plus bFGF grafts consisted predominantly of adipose tissue and had significantly less fibrosis but greater microvascular density compared with control and also grafts mixed with ASCs had a high expression of angiogenic factors. More importantly, the bFGF treated fat grafts shown elevate in survival, vascularization, and angiogenic factors expression when compared with the grafts that received ASCs alone. These results indicated that bFGF together with ASCs can enhance the efficacy of autologous fat transplantation and increase blood vessel generation involved in the benefits from bFGF.
Duodenal Aspirates for Small Intestine Bacterial Overgrowth: Yield, PPIs, and Outcomes after Treatment at a Tertiary Academic Medical Center
Authors: Franco Diana L. , Disbrow Molly B. , Kahn Allon , Koepke Laura M. , Harris Lucinda A. , Harrison M. Edwyn , Crowell Michael D. , Ramirez Francisco C.
Published: January 2015

Duodenal aspirates are not commonly collected, but they can be easily used in detection of small intestinal bacterial overgrowth (SIBO). Proton pump inhibitor (PPI) use has been proposed to contribute to the development of SIBO. We aimed to determine the yield of SIBO-positive cultures detected in duodenal aspirates, the relationship between SIBO and PPI use, and the clinical outcomes of patients identified by this method. In a retrospective study, we analyzed electronic medical records from 1263 consecutive patients undergoing upper endoscopy at a tertiary medical center. Aspirates were collected thought out the third and fourth portions of the duodenum, and cultures were considered to be positive for SIBO if they produced more than 100,000 cfu/mL. Culture analysis of duodenal aspirates identified SIBO in one-third of patients. A significantly higher percentage of patients with SIBO use PPIs than patients without SIBO, indicating a possible association. Similar proportions of patients with SIBO improved whether or not they received antibiotic treatment, calling into question the use of this expensive therapy for this disorder.
Evaluating the Effect of a Community-Based Lay Health Advisor Training Curriculum to Address Immigrant Children's Caries Disparities
Authors: Hsu Yuan-Jung , Peng Wu-Der , Chen Jen-Hao , Lin Ying-Chun , Chang Chin-Shun , Chen Ted , Hu Chih-Yang , Ho Pei-Shan , Chen Fu-Li , Lee Chien-Hung , Huang Hsiao-Ling
Published: January 2015

Previous programs had not designed the culturally adequate Lay Health Advisor (LHA) oral health training curriculum for medically underserved population. We evaluated the effects of LHA training curriculum for addressing immigrant children's caries disparities in their access to dental care. We used a pre/post-test study design. Immigrant women were recruited from churches, schools, and immigrant centers in an urban area. Four training classes were held. Each training cycle lasted 15 consecutive weeks, consisting of 1 weekly 2-h training session for 12 weeks followed by a 3-week practicum. The curriculum included training in caries-related knowledge, oral hygiene demonstrations, teaching techniques, communication skills, and hands-on practice sessions. Thirty-seven LHA trainees completed the course and passed the post-training exam. The data were collected using self-report questionnaires. The level of oral health knowledge, self-efficacy and attitudes toward oral hygiene were significantly increased after LHA training. There was a significant and over twofold increase in trainees' oral hygiene behaviors. An increase of >20% in LHA and their children's dental checkup was observed following training. After training, LHAs were more likely to have 3+ times of brushing teeth [Odds Ratio (OR) = 13.14], brushing teeth 3+ minutes (OR = 3.47), modified bass method use (OR = 30.60), dental flossing (OR = 4.56), fluoride toothpaste use (OR = 5.63) and child's dental visit (OR = 3.57). The cross-cultural training curriculum designed for immigrant women serving as LHAs was effective in improvement of oral hygiene behaviors and access to dental care.
Mortality and Cardiovascular Morbidity Associated with Haemoglobin Levels: A Pooled Analysis of Randomised Controlled Trials
Authors: Locatelli Francesco , de Francisco Angel , Deray Gilbert , Fliser Danilo , Armstrong Gillian , Dougherty Frank C. , Ehrhard Patricia
Published: January 2015

Background/Aims: Several randomised controlled trials (RCTs) have raised concerns about potential harm associated with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease patients, especially when haemoglobin (Hb) levels above 13 g/dl were targeted. We report the relationship between Hb levels and outcomes in the methoxy polyethylene glycol-epoetin beta RCT programme. Methods: We assessed the association between Hb and a composite end point, as well as its components [all-cause mortality, myocardial infarction (MI) or cerebrovascular events (CVE)], in multiple post hoc analyses of 9 prospective RCTs (3,405 chronic kidney disease patients). Mean Hb levels over time and deviation from target were analysed using a Cox regression model. Time-adjusted average Hb, deviation from target, the last Hb, Hb slope and within-patient Hb variability preceding an event were analysed using a time-dependent Cox model. Hazard ratios and 95% confidence intervals were calculated. Results: Average Hb <10 g/dl, decrease from stable baseline Hb >1 g/dl, last Hb <10 g/dl, Hb decline >1.5 g/dl/4 weeks and increased Hb variability were associated with a higher risk of the composite end point and all-cause mortality. An increased risk for CVE and MI was found with a last Hb <10 g/dl and with a decrease from baseline >1 g/dl in the preceding month. Conclusion: In multiple analyses from a large programme of prospective clinical trials of ESA treatment, risk of all-cause mortality and cardiovascular morbidity risk was consistently higher at Hb <10 g/dl and in patients whose Hb fell below target.
Therapeutic Advances in the Treatment of Polycystic Kidney Disease
Authors: Riella Cristian , Czarnecki Peter G. , Steinman Theodore I.
Published: January 2015

The spectrum of polycystic kidney disease (PKD) comprises a family of inherited syndromes defined by renal cyst formation and growth, progressive renal function loss and variable extrarenal manifestations. The most common form, autosomal-dominant PKD is caused by mutations in one of two genes, PKD1 or PKD2. Recent developments in genomic and proteomic medicine have resulted in the discovery of novel genes implicated in the wide variety of less frequent, recessive PKD syndromes. Cysts are the disease, and overall cystic burden, measured by MRI as total kidney volume, is being established as the best available biomarker of disease progression. Current state-of-the-art therapy is aimed at quality treatment for chronic renal insufficiency and cyst-related complications. Recent therapeutic studies have focused on mechanisms reducing intracellular cyclic AMP levels, blocking the renin-angiotensin-aldosterone system and inhibiting the mTOR-signaling pathway. PKD therapies with vasopressin antagonists and somatostatin analogues result in the reduction of intracellular cAMP levels and have shown limited clinical success, but side effects are prominent. Similarly, mTOR pathway inhibition has not shown significant therapeutic benefits. While the HALT-PKD study will answer questions by the end of 2014 about the utility of renin-angiotensin-aldosterone system blockade and aggressive blood pressure control, the next generation of PKD therapy studies targeting proliferative mechanisms of cyst expansion are already under way. Advances in research on the molecular mechanisms of cystogenesis will help design novel targeted PKD therapies in the future.
Pathogenesis of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis and Potential Targets for Biologic Treatment
Authors: Sanders J.S.F. , Abdulahad W.H. , Stegeman C.A. , Kallenberg C.G.M.
Published: January 2015

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are autoimmune diseases in which the small vessels are inflamed. Clinical observations suggest a pathogenic role for ANCA. Such a role is supported by in vitro experimental data and animal models, particularly for myeloperoxidase-ANCA. An in vivo pathogenic role of ANCA directed to proteinase 3 has, however, not been fully substantiated. Additionally, the pathogenic role of B cells, T cells, and the alternative pathway of complement in AAV have been elucidated. Insight into these pathogenic pathways involved in AAV has opened and will further open new ways for targeted biologic treatment. In this review the pathogenesis of AAV and potential targets for biologic treatment are discussed.
Eculizumab in the Treatment of Membranoproliferative Glomerulonephritis
Authors: Bomback Andrew S.
Published: January 2015

A major shift in our understanding of the membranoproliferative glomerulonephritis (MPGN) lesion is the focus on which components of the complement pathway are involved in mediating renal injury. Hence, MPGN is no longer classified solely by ultrastructural findings on biopsy but instead divided into immune complex-mediated lesions versus complement-mediated lesions. This emphasis on complement, in turn, leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anticomplement therapy, blocks at the level of C5 and has revolutionized the treatment of complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Whether this agent will work equally well for the far more heterogeneous complement-mediated MPGN lesions, also known as C3 glomerulopathy, remains unclear. To date, the experience and published data on using eculizumab in MPGN suggests this agent will work for some, but not all, patients with this pathologic lesion.
Kryptokokkose der Lunge mit Invasion der Trachealwand bei einem immunkompetenten Patienten: Fallbericht und Literaturübersicht
Authors: Sun Li , Chen Hui , Shao Changzhou , Song Yuanlin , Bai Chunxue
Published: January 2015

Kryptokokkosen weisen weltweit eine signifikante Morbidität und Mortalität auf. Die pulmonale Kryptokokkose ist eine subakute oder chronische Pilzerkrankung der Lunge. Wir stellen hier einen Fall von Kryptokokkose der Lunge mit karzinomähnlicher Invasion der Trachealwand bei einem immunkompetenten Patienten vor und geben einen Literaturüberblick. Der 44-jährige Nichtraucher klagte über leichte Dyspnoe und weißes Sputum, zeitweilig mit Blutspuren. In der Computertomographie (CT) des Thorax imponierten zwei potenziell maligne Läsionen im rechten Lungenhilus und im rechten Oberfeld der Lunge, die auch im Positronen-Emissions-Tomographie/CT-Scan (PET/CT-Scan) eine erhöhte Aufnahme von Fluordesoxyglucose zeigten. Die pathologische Untersuchung einer Lungenbiopsie-Probe ergab disseminierte Pilzsporen; die Perjodsäure-Schiff(PAS)-Färbung war positiv. Immunstatus und Blut-Tumormarker des Patienten waren durchgängig normal. Der Cryptococcus-Antigentiter betrug laut Latex-Agglutinationstest 1:1,280. In der Fiberbronchoskopie zeigte sich an der rechten Trachealwand eine prominente neue Raumforderung, die den rechten Hauptbronchus weitgehend blockierte. Um die Symptome der Atemwegsobstruktion zu lindern, wurde eine bronchoskopische Behandlung mit Ablation und endotrachealer Stent-Implantation durchgeführt. Da sich unter Itraconazol die Symptome verschlechterten, wurde auf Amphotericin-B-Liposome als Antimykotikum umgestellt. Durch diese Maßnahmen verbesserte sich der Befund. Wir gelangen zu der Schlussfolgerung, dass eine Kryptokokkose der Lunge im radiologischen und bronchoskopischen Erscheinungsbild einer Tumorerkrankung der Lunge ähneln und sogar bei immunkompetenten Patienten auftreten kann.
Association of de novo Dipstick Albuminuria with Severe Acute Kidney Injury in Critically Ill Septic Patients
Authors: Neyra Javier A. , Manllo John , Li Xilong , Jacobsen Gordon , Yee Jerry , Yessayan Lenar ,   for the AKICI Study Group
Published: January 2015

Background: Acute kidney injury (AKI) occurs frequently in septic patients. Albuminuria may play a role as an early marker of septic AKI. The potential association between de novo dipstick albuminuria (DA) and septic AKI has not been examined. Methods: We conducted a single-center observational cohort study of 423 critically ill septic patients without chronic kidney disease (CKD) or prior positive DA within 3 months before admission. The association between de novo DA within the first 24 h of presentation and AKI at 72 h was examined. Results: AKI was identified in 268/423 (63%) patients and 20/423 (4.7%) required dialysis. De novo DA was associated with AKI (univariate OR 1.91; 95% CI 1.27-2.86, p = 0.002). The association persisted in a multivariate logistic regression model adjusted for demographics, baseline kidney function, comorbidities, critical illness parameters, and exposure to nephrotoxins (adjusted OR 1.87; 95% CI 1.21-2.89, p = 0.005). The association between de novo DA and AKI was stronger for severe AKI, i.e. Acute Kidney Injury Network (AKIN) stage 3 (adjusted OR 2.99; 95% CI 1.52-5.85, p = 0.001) and AKIN stage 2 (adjusted OR 1.79; 95% CI 1.002-3.21, p = 0.049) but not AKIN stage 1 (adjusted OR 1.41; 95% CI 0.87-2.29, p = 0.16). Conclusions: De novo DA within the first 24 h of admission was independently associated with severe AKI in critically ill septic patients. Future studies are required to fully elucidate the utility of DA testing in the early detection and stratification of AKI.
Compared Decline of Residual Kidney Function in Patients Treated with Automated Peritoneal Dialysis and Continuous Ambulatory Peritoneal Dialysis: A Multicenter Study
Authors: Pérez Fontán Miguel , Remón Rodríguez César , Borràs Sans Mercè , Sánchez Álvarez Emilio , da Cunha Naveira Marta , Quirós Ganga Pedro , López-Calviño Beatriz , Rodríguez Suárez Carmen , Rodriguez-Carmona Ana
Published: January 2015

Background: There is controversy concerning the compared rates of decline of residual kidney function (RKF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). Objectives and Method: Following an observational, multicenter design, we studied 493 patients initiating peritoneal dialysis (PD) in four different Spanish units. We explored the effect of the PD modality on the rate of decline of RKF and the probability of anuria during follow-up. We applied logistic regression for intention-to-treat analyses, and linear mixed models to explore time-dependent variables, excluding those affected by indication bias. Main Results: Patients started on APD were younger and less comorbid than those initiated on CAPD. Baseline RKF was similar in both groups (p = 0.50). Eighty-seven patients changed their PD modality during follow-up. The following variables predicted a faster decline of RKF: higher (rate of decline) or lower (anuria) baseline RKF, younger age, proteinuria, nonprimary PD, use of PD solutions rich in glucose degradation products, higher blood pressure, and suffering peritonitis or cardiovascular events during follow-up. Overall, APD was not associated with a fast decline of RKF, but stratified analysis disclosed that patients with lower baseline RKF had an increased risk for this outcome when treated with this technique (HR: 2.26, 95% CI: 1.09-4.82, p = 0.023). Moreover, the probability of anuria during follow-up was overtly higher in APD patients (HR: 3.22, 95% CI: 1.25-6.69, p = 0.002). Conclusions: Starting PD patients directly on APD is associated with a faster decline of RKF and a higher risk of developing anuria than doing so on CAPD. This detrimental effect is more marked in patients initiating PD with lower levels of RKF.
Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats
Authors: Zhu Chaoyu , Xiao Yuanyuan , Liu Xiaohua , Han Junfeng , Zhang Jianmei , Wei Li , Jia Weiping
Published: January 2015

Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.
Effects of Three Kinds of Curcuminoids on Anti-Oxidative System and Membrane Deformation of Human Peripheral Blood Erythrocytes in High Glucose Levels
Authors: Yang Wei , Fu Juan , Yu Miao , Wang Di , Rong Ying , Yao Ping , Nüssler Andreas K. , Yan Hong , Liu Liegang
Published: January 2015

Background/Aims: Curcuminoids are the main bioactive constituents of the rhizome of turmeric. Erythrocytes lesions in diabetes are probably related to hyperglycemia and protein glycation. It has been reported that curcumin prevent lipid peroxidation. However, reports on the effects of demethoxycurcumin and bis-demethoxycurcumin on human erythrocytes at high glucose levels are scarce. Our aim is to investigate the effect of curcuminoids on oxidative stress and membrane of erythrocytes exposed to hyperglycemic condition. Methods: In this study, the different blood samples were treated with two doses of glucose (10 or 30 mM) to mimic hyperglycemia in the presence or absence of three kinds of curcuminoids (5 or 10 μM) in a medium at 37 °C for 24 h (Each experiment consists of 20 blood samples from 10 male and 10 female volunteers). The malondialdehyde was checked by HPLC, antioxidase (GSH and GSSG) were measured by LC/MS, SOD was checked by WST-1 kit, morphology and phospholipid symmetry were detected by flow cytometry, confocal scanning microscope and scanning electron microscope. Results: The results illustrated that all three curcuminoids reduce oxidative stress damage on the membrane and maintain a better profile for erythrocytes. Furthermore, three curcuminoids had benefit effects on antioxidase. Conclusion: The three kinds of curcuminoids supplementation may prevent lipid peroxidation at different intensity and membrane dysfunction of human erythrocytes in hyperglycemia.
Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression
Authors: Bitter Andreas , Nüssler Andreas K. , Thasler Wolfgang E. , Klein Kathrin , Zanger Ulrich M. , Schwab Matthias , Burk Oliver
Published: January 2015

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.
Advanced Oxidation Protein Products Induce Hypertrophy and Epithelial-To-Mesenchymal Transition in Human Proximal Tubular Cells through Induction of Endoplasmic Reticulum Stress
Authors: Tang Xun , Rong Guang , Bu Yang , Zhang Shaojie , Zhang Min , Zhang Jun , Liang Xiujie
Published: January 2015

Background: In chronic kidney disease (CKD), the accumulation of advanced oxidation protein products (AOPPs) is prevalent. Hypertrophy and epithelial-to-mesenchymal transition (EMT) of tubular cells are associated with the pathogenesis of CKD. However, whether AOPPs induce tubular-cell hypertrophy and EMT is unclear. In this study, we investigated the effect of AOPPs on human proximal tubular cells (HK-2 cells) and the mechanisms underlying tubular-cell hypertrophy and EMT in vitro. Methods: The mRNA and protein expression of CCAAT/enhancer-binding protein-homologous protein (CHOP), glucose-regulated protein (GRP) 78, p27, α-smooth muscle actin (α-SMA) and E-cadherin were evaluated by quantitative real-time PCR and western blot, respectively. Cell cycle was detected by flow cytometry. Bicinchoninic acid method was performed to measure total protein content. Results: AOPP treatment upregulated total protein expression, caused an increase in the percentage of G1-phase cells, and induced the overexpression of p27 and α-SMA, lowered the expression of E-cadherin. Furthermore, AOPP treatment induced the overexpression of GRP78 and CHOP. Moreover, the aforementioned effects were reversed following the treatment of cells with an NADPH oxidase inhibitor, a reactive oxygen species (ROS) scavenger, or salubrinal, which is an inhibitor of ER stress, whereas these effects were produced after exposure to thapsigargin, an inducer of ER stress. Conclusion: Our results suggest that AOPPs induced HK-2-cell hypertrophy and EMT by inducing ER stress, which was likely mediated by ROS. These findings could facilitate the development of novel therapeutic strategies for suppressing the progression of CKD.
Biodegradable Microparticles Containing Crotamine Isolated from Crotalus durissus terrificus Display Antileishmanial Activity in vitro
Authors: Macedo Sharon Rose A. , de Barros Neuza B. , Ferreira Amália S. , Moreira-Dill Leandro S. , Calderon Leonardo A. , Soares Andreimar M. , Nicolete Roberto
Published: January 2015

Background/Aims: To evaluate antileishmanial activity of crotamine, a toxin isolated from Crotalus durissus terrificus, in solution form and encapsulated in biodegradable microparticles in vitro. Methods: Particles were analyzed on-chip by surface plasmon resonance and characterized by testing their diameters, zeta potential and encapsulation rate. The viability of promastigotes as well as murine macrophages was assessed. Furthermore, the phagocytic index was determined for macrophages, and cell supernatants were collected for the determination of TNF-α levels. An infection assay using Leishmania amazonensis-infected macrophages was also conducted. Results: The diameters and zeta potential of control particles (1.35 μm; -12.3 mV) and of those containing crotamine (3.09 μm; -20.9 mV) were adequate for the assays conducted. Crotamine-loaded particles were better captured by macrophages than control particles (increase of 12% in the phagocytic index), leading to increased TNF-α levels (196 pg/ml), and they also induced a significant decrease in the numbers of amastigotes compared to infected macrophages only. Conclusion: The approach presented here opens the possibility of working with safe concentrations of encapsulated toxins to reach antileishmanial effects.
Effects of Peroxynitrite on Relaxation through the NO/sGC/cGMP Pathway in Isolated Rat Iliac Arteries
Authors: Tawa Masashi , Shimosato Takashi , Iwasaki Hirotaka , Imamura Takeshi , Okamura Tomio
Published: January 2015

Background/Aims: The present study investigated the mechanism by which peroxynitrite impairs vascular function through the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway. Methods: Mechanical responses of rat external iliac arteries without endothelium were studied under exposure to peroxynitrite. cGMP concentrations were determined by enzyme immunoassay. Results: Relaxation induced by BAY 41-2272 (sGC stimulator) was impaired under exposure to peroxynitrite, whereas that by BAY 60-2770 (sGC activator) was enhanced. These responses were correlated with tissue levels of cGMP. Effects of peroxynitrite on the relaxant responses to BAY compounds were also observed in the presence of superoxide dismutase (SOD) or tempol, both of which scavenge a certain kind of reactive molecules other than peroxynitrite. As is the case with the relaxant response to BAY 41-2272, acidified NaNO2- and nitroglycerin-induced relaxations were markedly attenuated by exposing the arteries to peroxynitrite, which was not abolished by preincubation with SOD or tempol. On the other hand, peroxynitrite exposure had no effect on the 8-Br-cGMP-induced vasorelxation. Conclusion: These findings suggest that peroxynitrite interferes with the NO/sGC/cGMP pathway by altering the redox state of sGC. It is likely that peroxynitrite can shift the sGC redox equilibrium to the NO-insensitive state in the vasculature.
Effects of 1,2,3,4-Tetrahydroisoquinoline Derivatives on Dopaminergic Spontaneous Discharge in Substantia Nigra Neurons in Rats
Authors: Chiba Hikari , Sato Haruka , Abe Kenji , Saito Toshiaki , Horiguchi Yoshie , Nojima Hiroshi , Taguchi Kyoji
Published: January 2015

1,2,3,4-Tetrahydroisoquinoline (TIQ) and its derivatives, 1-methyl-TIQ (1-MeTIQ) and 1-benzyl-TIQ (1-BnTIQ), are endogenously present in the human brain. In this study, we compared the effects of TIQ derivatives on spontaneous nigral dopaminergic discharge in rats treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the low-to-middle dose range (0.01-1 mg/kg), intravenous administration of MPTP induced a transient and potent increase in the firing rate. TIQ (0.01-30 mg/kg) had no effects, and 1-MeTIQ and 1-BnTIQ (0.01-10 mg/kg) produced a weaker increase in the firing frequency immediately after intravenous administration. Pretreatment with 1-MeTIQ (80 mg/kg, i.p.) significantly inhibited the decrease in dopaminergic spontaneous firing induced by a high dose of MPTP. The nigral induction of thiobarbituric acid-reactive substances (TBARS) by MPTP was also significantly suppressed by pretreatment with 1-MeTIQ. These results suggest that the neurotoxicity induced by TIQ derivatives is relatively weak compared to that induced by MPTP. The neuroprotective effect of 1-MeTIQ from MPTP-induced toxicity may be partially due to a decrease in free radicals, as suggested by a decrease in TBARS. This action presumably prevents cell membrane degeneration.
Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Authors: Huang Qunhua , Zhou Huanjiao Jenny , Zhang Haifeng , Huang Yan , Hinojosa-Kirschenbaum Ford , Fan Peidong , Yao Lina , Belardinelli Luiz , Tellides George , Giordano Frank J. , Budas Grant R. , Min Wang
Published: January 2015

Background—

Thioredoxin 2 (Trx2) is a key mitochondrial protein that regulates cellular redox and survival by suppressing mitochondrial reactive oxygen species generation and by inhibiting apoptosis stress kinase-1 (ASK1)–dependent apoptotic signaling. To date, the role of the mitochondrial Trx2 system in heart failure pathogenesis has not been investigated.

Methods and Results—

Western blot and histological analysis revealed that Trx2 protein expression levels were reduced in hearts from patients with dilated cardiomyopathy, with a concomitant increase in ASK1 phosphorylation/activity. Cardiac-specific Trx2 knockout mice develop spontaneous dilated cardiomyopathy at 1 month of age with increased heart size, reduced ventricular wall thickness, and a progressive decline in left ventricular contractile function, resulting in mortality due to heart failure by ≈4 months of age. The progressive decline in cardiac function observed in cardiac-specific Trx2 knockout mice was accompanied by the disruption of mitochondrial ultrastructure, mitochondrial membrane depolarization, increased mitochondrial reactive oxygen species generation, and reduced ATP production, correlating with increased ASK1 signaling and increased cardiomyocyte apoptosis. Chronic administration of a highly selective ASK1 inhibitor improved cardiac phenotype and reduced maladaptive left ventricular remodeling with significant reductions in oxidative stress, apoptosis, fibrosis, and cardiac failure. Cellular data from Trx2-deficient cardiomyocytes demonstrated that ASK1 inhibition reduced apoptosis and reduced mitochondrial reactive oxygen species generation.

Conclusions—

Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial reactive oxygen species production and ASK1-dependent apoptosis. Inhibition of ASK1 represents a promising therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure.
Cardiac Hemodynamics are Linked With Structural and Functional Features of Brain Aging: The Age, Gene/Environment Susceptibility (AGES)‐Reykjavik Study
Authors: Sabayan Behnam , van Buchem Mark A. , Sigurdsson Sigurdur , Zhang Qian , Harris Tamara B. , Gudnason Vilmundur , Arai Andrew E. , Launer Lenore J.
Published: January 2015

Background

Advanced heart failure is linked with structural and functional alterations in the brain. It is unclear whether a graded decrease in cardiac function puts older subjects at risk for brain aging. We investigated the association between cardiac hemodynamics and features of brain aging in community‐dwelling older subjects.

Methods and Results

With data from a sub‐study (n=931 subjects, mean age 75.9 years, 47.7% male) of the Age, Gene/Environment Susceptibility (AGES)‐Reykjavik Study, we investigated the association of
MRI
measures of cardiac hemodynamics, including left ventricular stroke volume (
LVSV
) and cardiac output (
CO
) to brain characteristics. In multivariable analyses, each 10 mL lower
LVSV
was associated with 4.4 mL (95%
CI
1.9 to 6.9) lower total parenchymal brain volume (
TBV
) and 3.7 mL (95%
CI
1.8 to 5.7) lower gray matter volume (
GMV
). Likewise, each unit (L/min) lower
CO
was associated with 3.9 mL (95%
CI
0.4 to 7.4) lower
TBV
and 3.9 mL (95%
CI
0.4 to 7.4) lower
GMV
. Lower
LVSV
was associated with worse performance in processing speed (
P
=0.043) and executive function (
P
<0.001). Lower
CO
was associated with worse performance in processing speed (
P
=0.015) and executive function (
P
=0.003). Each 10 mL lower
LVSV
and each unit lower
CO
associated with a higher risk of mild cognitive impairment or dementia (odds ratio: 1.24, 95%
CI
0.99 to 1.57 and odds ratio: 1.40, 95%
CI
0.99 to 2.00, respectively).

Conclusions

A graded decrease in cardiac functioning is associated with features of brain aging
.
Older persons with cardiac or cognitive signs and symptoms may have both cardiac and cerebral diseases and should be evaluated accordingly.
Cardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of
Toll‐like Receptor 2
and Dietary Flavonoid Intake
Authors: Zhong Jia , Colicino Elena , Lin Xinyi , Mehta Amar , Kloog Itai , Zanobetti Antonella , Byun Hyang‐Min , Bind Marie‐Abèle , Cantone Laura , Prada Diddier , Tarantini Letizia , Trevisi Letizia , Sparrow David , Vokonas Pantel , Schwartz Joel , Baccarelli Andrea A.
Published: January 2015

Background

Short‐term fine particles (
PM
2.5
) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether
Toll‐like receptor 2
(

TLR
2

) methylation, a reversible immune‐epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following
PM
2.5
exposure.

Methods and Results

We measured heart rate variability and
PM
2.5
repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood

TLR
2

methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (
FFQ
). Every 10 μg/m
3
increase in 48‐hour
PM
2.5
moving average was associated with 7.74% (95%
CI
: −1.21% to 15.90%;
P
=0.09), 7.46% (95%
CI
: 0.99% to 13.50%;
P
=0.02), 14.18% (95%
CI
: 1.14% to 25.49%;
P
=0.03), and 12.94% (95%
CI
: −2.36% to 25.96%;
P
=0.09) reductions in root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency power, and high‐frequency power, respectively. Higher

TLR
2

methylation exacerbated the root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency, and high‐frequency reductions associated with heightened
PM
2.5
(
P
interaction
=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile‐range increase in flavonoid intake was associated with 5.09% reduction in mean

TLR
2

methylation (95%
CI
: 0.12% to 10.06%;
P
=0.05) and counteracted the effects of
PM
2.5
on low frequency (
P
interaction
=0.05). No significant effect of methyl nutrients on

TLR
2

methylation was observed.

Conclusions

Higher

TLR
2

methylation may confer susceptibility to adverse cardiac autonomic effects of
PM
2.5
exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing

TLR
2

methylation.
Analysis of Tissue Plasminogen Activator Eligibility by Sex in the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Madsen Tracy E. , Khoury Jane C. , Alwell Kathleen A. , Moomaw Charles J. , Kissela Brett M. , De Los Rios La Rosa Felipe , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L. , Khatri Pooja , Ferioli Simona , Kleindorfer Dawn
Published: January 2015

Background and Purpose—

Sex differences in recombinant tissue-type plasminogen activator (r-tPA) administration are present in some populations. It is unknown whether this is because of eligibility differences or the modifiable exclusion criterion of severe hypertension. Our aim was to investigate sex differences in r-tPA eligibility, in individual exclusion criteria, and in the modifiable exclusion criterion, hypertension.

Methods—

We included all ischemic stroke patients ≥18 years among residents of the Greater Cincinnati/Northern Kentucky region who presented to 16-area emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association (AHA) and European Cooperative Acute Stroke Study (ECASS) III guidelines.

Results—

Of 1837 ischemic strokes, 58% were women, 24% were black. Mean age in years was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex (6.8% men and 6.1% women;
P
=0.55), even after adjusting for age (7.0% and 5.9%;
P
=0.32). Similar proportions of women and men arrived beyond 3- and 4.5-hour time windows, but more women had severe hypertension. There were no sex differences in blood pressure treatment rates among those with severe hypertension (14.6% women and 20.8% men;
P
=0.21). More women were >80 years and had National Institutes of Health Stroke Scale (NIHSS) >25.

Conclusions—

Within a large, biracial population, eligibility for r-tPA was similar by sex. Women were more likely to have the modifiable exclusion criterion of severe hypertension but were not more likely to be treated. Women were more likely to have 2 of the 5 ECASS III exclusion criteria. Undertreatment of hypertension in women is a potentially modifiable contributor to reported differences in r-tPA administration.
Relationship Between Degree of Left Ventricular Dysfunction, Symptom Status, and Risk of Embolic Events in Patients With Atrial Fibrillation and Heart Failure
Authors: Sandhu Roopinder K. , Hohnloser Stefan H. , Pfeffer Marc A. , Yuan Fei , Hart Robert G. , Yusuf Salim , Connolly Stuart J. , McAlister Finlay A. , Healey Jeff S.
Published: January 2015

Background and Purpose—

Limited data exists regarding the relationship between left ventricular systolic dysfunction (LVSD) and heart failure (HF) symptoms and embolic risk among patients with atrial fibrillation.

Methods—

Participants in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF, but not randomized to oral anticoagulation, were categorized as having preserved versus reduced ejection fraction. If reduced, LVSD was classified as mild, moderate, or severe. Symptoms were quantified using New York Heart Association class.The primary outcome was a composite of stroke, transient ischemic attack, and systemic embolism.

Results—

There were 3487 antiplatelet-treated patients with HF at baseline. Of these patients, 969 (46.8%) had HF with preserved ejection fraction and 1103 (53.2%) had HF with reduced ejection fraction. During 3.6 years of mean follow-up, first occurrence of stroke, transient ischemic attack, or systemic embolism occurred in 386 patients.The strongest independent predictors of embolic events were age ≥75 years (hazard ratio 2.55; confidence interval, 1.85–3.53), prior stroke or transient ischemic attack (hazard ratio 2.07; 95% confidence interval, 1.65–2.60), and female sex (hazard ratio 1.37; confidence interval, 1.11–1.69). However, ejection fraction <0.50, degree of LVSD, and New York Heart Association class did not predict embolic events. Patients with HF with preserved ejection fraction exhibited similar risk of embolic events as those with HR with reduced ejection fraction: 4.3% versus 4.4% per 100 person-years (hazard ration 1.01; 95% confidence interval, 0.78–1.31). Risk of embolic events was similar across categories of LVSD (
P
for trend =0.96) and New York Heart Association class (
P
for trend =0.57).

Conclusion—

Among HF patients in ACTIVE, neither the presence of LVSD or degree of symptom severity influenced risk of embolic events.
Воспоминания российских офицеров как источник по истории русско-турецкой войны 1828–1829 гг. (на примере А.И. Михайловского-Данилевского и Ф.Ф. Торнау)
Authors: Гоков О.А.
Published: January 2015

“Memories of Russian officers as a source on the history of Russian-Turkish war of 1828–1829. (On an example of A.I. Mikhailovsky-Danilevsky and F.F. Tornau)”. In the article is made a comparative analysis of the memoirs of officers of various links of the Russian army on the Russian-Turkish war of 1828-1829. A.I. Mikhailovsky-Danilevsky had little personal experience of participation in the immediate life of troops in a campaign in 1829. Therefore his generalizing opinion, as a manager, paradoxically combined with the low informativeness. F.F. Tornau has passed campaign in 1829 at the lowest officer posts of the General Staff. Therefore, his memories more deeply and versatile. Informative component of sources is divided us into four blocks. A significant place in the memoirs is given to life of the rearward and the army. However, it is mainly the life of the officers. Soldier's everyday life in these memoirs practically not displayed.
A new synonym and a new combination in Stipa aliena Keng (Poaceae: Stipa sect. Regelia)
Authors: Nobis Marcin , Nowak Arkadiusz , Gudkova Polina D
Published: January 2015

Stipa section Regelia comprises three species occurring in mountainous areas of Central Asia. One of them, S. smithii, was described by Martinovský in 1970, but the taxon has been overlooked in later taxonomical studies. The species was described with two varieties, var. smithii and var. macrocarpa. As a result of our taxonomical studies, we find the typical variety of the taxon to be conspecific with Stipa aliena, and propose that the second one be recognized as Stipa aliena var. macrocarpa comb. nov. Remarks on species belonging to section Regelia and micromorphological patterns of their lemma morphologies are discussed. A key to species close to S. aliena is provided.
New lectotypification of Crotalaria incana var. australis (Crotalarieae, Fabaceae): An example of procedure to determine the correct types from the Lorentz & Hieronymus collection
Authors: Planchuelo Ana María , ESPINAR LUIS ARIZA
Published: January 2015

The first collections of Crotalaria incana from central Argentina were analyzed with special attention to specimens collected by P. Lorentz & G. Hieronymus housed at CORD, GOET, and SI (fragments ex CORD) that are syntypes of Crotalaria incana var. australis. The previous designation of P. Lorentz & G. Hieronymus 242 (CORD) as a lectotype is not correct as this sheet is not original material and therefore must be considered to be a neotype. Here we designate P. Lorentz & G. Hieronymus 242 (GOET) as the lectotype of the variety.
Oribatid mites (Acari, Oribatida) in Soils of the Russian Far East
Authors: RYABININ NIKOLAY A.
Published: January 2015

The present paper reviews the taxonomic studies of the mite suborder Oribatida in the Russian Far East and gives a checklist of 596 species and subspecies in 228 genera, representing 84 families. The checklist includes data from more than 230 habitats of the Russian Far East from Chukotka to the Southern Primorye. In addition, a short historical and biogeographical review of oribatid mites study in the Russian Far East is presented.
Two new genera and one new species of Pantheinae from East Asia (Lepidoptera, Noctuidae: Pantheinae). Revision of Pantheinae, contribution XI
Authors: Behounek G. , HAN H.L. , Kononenko V.S.
Published: January 2015

Two new genera, Pantheaforma gen. n. (Type-species Pantheaforma ihlei sp. n.) and Chrisotea gen. n. (Type-species Trichosea zhangi Chen, 1990) from East Asia and a new species Pantheaforma ihlei sp. n. from Thailand and Myanmar are described. New combination Chrisotea zhangi (Chen, 1990), comb. n. is proposed. New taxa are illustrated with imagines in colour and male and female genitalia. The little-known species Pantheana yangzisherpana Hreblay, 1998, formerly only known from Nepal is reported for China for the first time.