bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12-month randomized, prospective, open- label trial
Authors: Torres Dawn M. , Jones Frances J. , Shaw Janet C. , Williams Christopher D. , Ward John A. , Harrison Stephen A.
Published: July 2011

Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for (NASH). The aim of this randomized, open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan, compared to rosiglitazone alone, after 48 weeks of therapy. A total of 137 subjects with biopsy-proven NASH were enrolled and randomly assigned to receive either 4 mg twice-daily of rosiglitazone, 4 mg of rosiglitazone and 500 mg of metformin twice-daily, or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks. Patients were screened for other etiologies of chronic liver disease, including daily alcohol intake in excess of 20 g. Repeat liver biopsy was performed after 48 weeks of therapy and reviewed in a blinded fashion by a single expert hepatopathologist. The primary aim of the study was to assess for differences between treatment groups in the improvement of steatosis, hepatocellular inflammation, and fibrosis. In total, 108 subjects completed the trial. Primary outcome revealed no significant difference between treatment groups in all histologic parameters (steatosis, P = 0.137; hepatocellular inflammation, P = 0.320; fibrosis, P = 0.229). Overall improvement in steatosis, hepatocellular inflammation, ballooning degeneration, and fibrosis was observed (P ≤ 0.001). Serum aminotransferases were reduced in all three groups (P < 0.001 within treatment, P > 0.05 between groups). Metformin did not significantly mitigate weight gain (P = 0.051). Conclusions: Forty-eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology. (Hepatology 2011;)
Endothelial nitric oxide synthase is a key mediator of hepatocyte proliferation in response to partial hepatectomy in mice
Authors: Mei Yu , Thevananther Sundararajah
Published: July 2011

Endothelial nitric oxide synthase (eNOS) is a critical modulator of vascular tone and blood flow and plays major roles in liver physiology and pathophysiology. Nitric oxide (NO) is widely recognized as one of the key humoral factors important for the initiation of liver regeneration in response to partial hepatectomy. Liver regeneration in response to partial hepatectomy is dependent on the efficiency of growth factor-mediated cell-cycle progression. Epidermal growth factor receptor (EGFR) is a critical mediator of multiple hepatic mitogens, such as epidermal growth factor (EGF), transforming growth factor alpha, amphiregulin, and heparin-binding EGF in regenerating livers. However, the functional significance of endothelial nitric oxide synthase (eNOS) expressed in hepatocytes, and its potential role in EGFR-mediated hepatocyte proliferation, remains unexplored. We sought to determine whether eNOS is essential for hepatocyte proliferation in response to partial hepatectomy (PH). Our studies with eNOS knockout (eNOS−/−) mice suggest that eNOS activation is essential for the efficient induction of early events and elicitation of a robust hepatocyte proliferative response to PH. Moreover, eNOS expression is essential for the efficient early induction of matrix metalloprotease-9, a known mediator of extracellular matrix remodeling and growth factor activation in regenerating livers. Our in vitro studies suggest that eNOS is a critical mediator of EGF-induced hepatocyte proliferation, potentially via its influence on the induction of early growth response-1 (Egr-1) and phosphorylation of c-Jun—known mediators of cell-cycle progression. EGF-induced eNOS phosphorylation at Ser 1177 is dependent on the phosphorylation and activation of EGFR/PI3 kinase/AKT signaling in hepatocytes. Conclusion: Collectively, these results highlight a hitherto unrecognized role for eNOS activation in hepatocyte proliferation with implications for targeted therapies to enhance liver regenerative response in chronic disorders. (Hepatology 2011;)
Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis
Authors: Jia Ya-Li , Shi Lei , Zhou Jun-Nian , Fu Chun-Jiang , Chen Lin , Yuan Hong-Feng , Wang Yun-Fang , Yan Xin-Long , Xu Ying-Chen , Zeng Quan , Yue Wen , Pei Xue-Tao
Published: July 2011

The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result of frequent metastasis and tumor recurrence. Unfortunately, the underlying molecular mechanisms driving HCC metastasis are still not fully understood. It has been demonstrated that tumor stroma cells contribute to primary tumor growth and metastasis. Within the HCC environment, activated hepatic stellate cells (HSCs) can release a number of molecules and enhance cancer cell proliferation and invasiveness in a paracrine manner. Here, for the first time, we demonstrate that epimorphin (EPM; also called syntaxin-2), an extracellular protein, is strongly elevated in activated HSCs within tumor stroma. We show that knockdown of EPM expression in HSCs substantially abolishes their effects on cancer cell invasion and metastasis. Ectopic expression of EPM in HCC cancer cells enhances their invasiveness; we demonstrate that the cells expressing EPM have markedly increased metastasis potential. Furthermore, EPM-mediated invasion and metastasis of cancer cells is found to require up-regulation of matrix metalloproteinase-9 (MMP-9) through the activation of focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) axis. Conclusion: Our results show that EPM, secreted by activated HSCs within HCC stroma, promotes invasion and metastasis of cancer cells by activating MMP-9 expression through the FAK-ERK pathway. (Hepatology 2011;)
Septal elicitation of hippocampal theta rhythm did not repair cognitive and emotional deficits resulting from vestibular lesions
Authors: Neo Phoebe , Carter Donna , Zheng Yiwen , Smith Paul , Darlington Cynthia , McNaughton Neil
Published: July 2011

Bilateral vestibular lesions cause atrophy of the hippocampus in humans and subsequent deficits in spatial memory and the processing of emotional stimuli in both rats and humans. Vestibular lesions also impair hippocampal theta rhythm in rats. The aim of the present study was to investigate whether restoring theta rhythm to the hippocampus of a rat, via stimulation of the medial septum, would repair the deficits caused by vestibular lesions. It was hypothesized that the restoration of theta would repair the deficits and the vestibular rats would exhibit behavior and EEG similar to that of the sham rats. Rats were given either sham surgery or bilateral vestibular deafferentation (BVD) followed in a later operation by electrode implants. Half of the lesioned rats received stimulation. Subjects were tested in open field, elevated T‐maze and spatial nonmatching to sample tests. BVD caused a deficit in hippocampal theta rhythm. Stimulation restored theta power at a higher frequency in the vestibular‐lesioned rats, however, the stimulation did not repair the cognitive and emotional deficits caused by the lesions. It was concluded that stimulation, at least in the form used here, would not be a viable treatment option for vestibular damaged humans. © 2011 Wiley Periodicals, Inc.
Dorsal hippocampal lesions boost performance in the rat sequential reaction time task
Authors: Eckart M.T. , Huelse‐Matia M.C. , Schwarting R.K.W.
Published: July 2011

It is commonly accepted that the hippocampus plays a major role in declarative memory across species and that it is of particular relevance for spatial memory in rodents. However, the interplay between hippocampal function and nondeclarative memory systems, such as procedural stimulus‐response (S‐R) or sequential learning, is less clear: depending on task requirements, an interaction, dissociation or interference between hippocampal function and other memory systems may occur.

This study was conducted to investigate the influence of dorsal ibotenic hippocampal lesions on learning and performance of sequential behavior in a rat version of the serial reaction time task (SRTT). Magnetic resonance imaging (MRI) analyses of the lesions revealed a bilateral volume reduction of ∼ 46% (histological analyses: ∼59%) of the total hippocampus. They were largely confined to its dorsal part and led to an expected spatial memory deficits in an object place recognition test as compared to healthy controls, even though sham lesions had the same effect. Our earlier studies on sequential learning had revealed substantial impairments in case of dorsal striatal dopaminergic lesions. In the present study, however, hippocampal lesioned animals unexpectedly showed superior performance throughout SRTT testing and training as compared to controls, which resulted in a higher degree of subsequent automated sequential behavior. Thus, our data reveal the infrequent case where hippocampal lesions lead to long‐term improvements in test performance of a type of rather complex procedural behavior. One possible explanation for this effect is that hippocampal activity in rodents can interfere with other memory systems during the acquisition of procedural tasks with very low spatial requirements, as used here. Alternative explanations for the observed superior SRTT performance in lesioned animals, such as hyperactivity or increased exploratory drive are also topic of the discussion. © 2011 Wiley Periodicals, Inc.
Therapeutic factors secreted by mesenchymal stromal cells and tissue repair
Authors: Lee Ryang Hwa , Oh Joo Youn , Choi Hosoon , Bazhanov Nikolay
Published: July 2011

Systemic administration of MSCs resulted in remarkable functional improvements in injured tissues without either long‐term engraftment or differentiation in many clinical and experimental situations. Emerging evidence suggest that most of the beneficial effects of MSCs could be explained by secretion of soluble factors that have multiple effects including modulation of inflammatory and immune reactions, protection from cell death, and stimulation of endogenous progenitor cells. In this review, we focus on the therapeutic factors that account for the beneficial effects of MSCs in animal models of human diseases. J. Cell. Biochem. 112: 3073–3078, 2011. © 2011 Wiley Periodicals, Inc.
Contra‐regulation of calcium‐ and integrin‐binding protein 1‐induced cell migration on fibronectin by PAK1 and MAP kinase signaling
Authors: Naik Meghna U. , Naik Ulhas P.
Published: July 2011

Calcium‐ and integrin‐binding protein 1 (CIB1) has been shown to be involved in cell spreading and migration. The signaling events regulated by CIB1 during cell migration are poorly understood. Here we found that accumulation of CIB1 at the tip of the filopodia requires an intact cytoskeleton. Depletion of CIB1 using shRNA affects formation of FAK‐ and phosphotyrosine‐rich focal adhesions without affecting stress fiber formation. Overexpression of CIB1 results in cell migration on fibronectin and Erk1/2 MAP kinase activation. CIB1‐induced cell migration is dependent upon Erk1/2 activation, since it is inhibited by the MEK‐specific inhibitor PD98059. Furthermore, CIB1‐induced cell migration, as well as Erk1/2 activation, is dependent on PKC, Src family kinases as well as PI‐3 kinase as it is inhibited by bisindolylmaleimide 1, PP2, and wortmannin, respectively, in a dose‐dependent manner. Co‐expression of dominant‐negative Cdc42 completely abolished CIB1‐induced cell migration. Additionally, co‐expression of constitutively active, but not dominant negative PAK1, a CIB1 binding protein, inhibited CIB1‐induced cell migration. These results suggest that CIB1 positively regulates cell migration and is necessary for the recruitment of FAK to the focal adhesions. Furthermore, CIB1‐induced cell migration is dependent on MAP kinase signaling and its function is attenuated by PAK1. J. Cell. Biochem. 112: 3289–3299, 2011. © 2011 Wiley Periodicals, Inc.
Nobiletin, a polymethoxylated flavonoid from citrus, shows anti‐angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model
Authors: Lam Kai Heng , Alex Deepa , Lam In Kei , Tsui Stephen Kwok Wing , Yang Zi Feng , Lee Simon Ming Yuen
Published: July 2011

Traditional Chinese medicinal herbs are a rich source of compounds with reported anti‐inflammatory and anti‐carcinogenic effects. Growing evidence shows the codependence of chronic inflammation and angiogenesis, and the potential benefits of targeting angiogenesis in the treatment of chronic inflammation and targeting inflammation in the treatment of diseases with impaired angiogenesis. We hypothesized that the anti‐inflammatory activity of the natural compounds may owe at least some of its efficacy to their anti‐angiogenic activity and hence we investigated the anti‐angiogenic activity of these compounds in vivo in zebrafish embryos and in vitro in human umbilical vein endothelial cells (HUVECs). Nobiletin, a polymethoxylated flavonoid from citrus fruits, showed anti‐angiogenic activity in both assays. Nobiletin inhibited the formation of intersegmental vessels (ISVs) in live transgenic zebrafish embryos expressing green fluorescent protein (GFP) in the vasculature. Cell cycle analysis of dissociated zebrafish embryo cells showed that nobiletin induced G0/G1 phase accumulation in a dose‐dependent manner in GFP‐positive endothelial cells. Nobiletin also dose‐dependently induced VEGF‐A mRNA expression. In HUVECs, nobiletin inhibited endothelial cell proliferation and, to a greater extent, tube formation in a dose‐dependent manner. As in the in vivo study, nobiletin induced G0/G1 cell cycle arrest in HUVECs. However, this arrest was not accompanied by an increase in apoptosis, indicating a cytostatic effect of nobiletin. This study, for the first time, identifies nobiletin as having potent anti‐angiogenic activity and suggests that nobiletin has a great potential for future research and development as a cytostatic anti‐proliferative agent. J. Cell. Biochem. 112: 3313–3321, 2011. © 2011 Wiley Periodicals, Inc.
Bone‐metastatic prostate carcinoma favors mesenchymal stem cell differentiation toward osteoblasts and reduces their osteoclastogenic potential
Authors: Fritz V. , Brondello J.M. , Gordeladze J.O. , Reseland J.E. , Bony C. , Yssel H. , Noël D. , Jorgensen C.
Published: July 2011

Bone homeostasis is achieved by the balance between osteoclast‐dependent bone resorption and osteoblastic events involving differentiation of adult mesenchymal stem cells (MSCs). Prostate carcinoma (PC) cells display the propensity to metastasize to bone marrow where they disrupt bone homeostasis as a result of mixed osteolytic and osteoblastic lesions. The PC‐dependent activation of osteoclasts represents the initial step of tumor engraftment into bone, followed by an accelerated osteoblastic activity and exaggerated bone formation. However, the interactions between PC cells and MSCs and their participation in the disease progression remain as yet unclear. In this study, we show that bone metastatic PC‐3 carcinoma cells release factors that increase the expression by human (h)MSCs of several known pro‐osteoblastic commitment factors, such as α5/β1 integrins, fibronectin, and osteoprotegerin. As a consequence, as shown in an osteogenesis assay, hMSCs treated with conditioned medium (CedM) derived from PC‐3 cells have an enhanced potential to differentiate into osteoblasts, as compared to hMSCs treated with control medium or with CedM from non‐metastatic 22RV1 cells. We demonstrate that FGF‐9, one of the factors produced by PC‐3 cells, is involved in this process. Furthermore, we show that PC‐3 CedM decreases the pro‐osteoclastic activity of hMSCs. Altogether, these findings allow us to propose clues to understand the mechanisms by which PC favors bone synthesis by regulating MSC outcome and properties. J. Cell. Biochem. 112: 3234–3245, 2011. © 2011 Wiley Periodicals, Inc.
Improved electricity production from sewage sludge under alkaline conditions in an insert‐type air‐cathode microbial fuel cell
Authors: Yuan Yong , Chen Qing , Zhou Shungui , Zhuang Li , Hu Pei
Published: July 2011

BACKGROUND: Electricity can be generated directly from sewage sludge with a microbial fuel cell (MFC), combining degradation of organic matter. This study constructed a novel insert‐type air‐cathode microbial fuel cell (ITAC‐MFC) as an alternative to a sediment‐type MFC and a two‐chambered MFC for the generation of bioelectricity and the degradation of sewage sludge organic matter. Meanwhile, a pH adjustment was carried out to enhance substrate bioavailability of sludge and to suppress methane production in the MFC.

RESULTS: A maximum power density of 73 ± 5 mW m−2 was obtained at sludge pH 10.0, much higher than those of 33 ± 3 and 4 ± 0.5 mW m−2 obtained at pH 8.0 and 6.0, respectively. It was observed that the soluble chemical oxygen demand (SCOD) of sewage sludge at pH 10.0 was almost three times greater than that at pH 6.0. At the same time, the total chemical oxygen demand (TCOD) removal and coulombic efficiency (CE) at pH 10.0 were also much higher than at the other two conditions.

CONCLUSIONS: The results demonstrated that improved electricity production and organic degradation could be achieved by maintaining the sludge pH at 10.0 in an MFC. ITAC‐MFC offers an attractive alternative for the environmentally‐friendly removal of organic matter in sewage sludge. Copyright © 2011 Society of Chemical Industry
POWER AND INTERESTS IN INFORMATION AND COMMUNICATION AND DEVELOPMENT: EXOGENOUS AND ENDOGENOUS DISCOURSES IN CONTENTION
Authors: Mansell Robin
Published: July 2011

This paper illustrates the persistence of an exogenous model of development that underpins many interventions aimed at employing information and communication technologies (ICTs) to meet development goals. The analysis is based on a sample of texts from reports produced by United Nations agencies and the World Bank. The aim is to show how the discourse on ICT interventions invariably is reminiscent of a dominant exogenous model even when alternative models with respect to development are seen to influence policy and practice. It is argued that practice‐based, emergence approaches offer an attractive, although insufficient, way forward. Copyright © 2011 John Wiley & Sons, Ltd.
MANAGING RISK IN SMALL STEPS: ACHIEVING LANDSLIDE RISK REDUCTION BY STRATEGIC INCREMENTALISM IN THE EASTERN CARIBBEAN
Authors: Anderson Malcolm G. , Holcombe Elizabeth
Published: July 2011

Understanding landslide processes in developing counties, coupled with community engagement can deliver landslide hazard reduction ‘on the ground’, leading to behavioural change within communities and governments. On this basis, we undertook a ‘strategic incrementalism’ approach to landslide risk reduction. The change achieved in stakeholder engagement was simultaneously a major challenge and the determinant of the project success. However, the resulting stakeholder commitment demonstrates the clear benefit of designing risk reduction measures that deliver research, on‐the‐ground reduction of risk and behavioural change and provides specific evidence that strategic incrementalism is a viable process. Copyright © 2011 John Wiley & Sons, Ltd.
Benefit Fraud Investigative Interviewing: A Self‐Report Study of Investigation Professionals' Beliefs Concerning Practice
Authors: Walsh Dave , Bull Ray
Published: July 2011

Previous studies into the quality of investigating interviewing of suspects conducted in criminal investigations in England and Wales have almost exclusively focused on the skills and tactics employed by interviewing officers during interviews. However, interviewing officers are trained in an interviewing framework that includes the importance of evaluating interviews as a means of improving skills. In light of the scarcity of research concerning the evaluation task, this study examined perceptions of benefit fraud investigation personnel. A questionnaire was answered by 114 respondents including investigators, investigation managers, investigation trainers, and investigation inspectors. From their responses, it was evident that there was an understanding of the necessary skills required to conduct interviews. However, after comparing these responses with the actual interviewing practice of benefit fraud investigators, there was found to be a gap between these beliefs and practice. The findings suggest that although it is agreed what interviewing skills are required to conduct interviews, investigators and managers do not accurately reflect upon whether these skills are actually employed in interviews. This suggests that evaluation of interviews is being neglected and may well explain why research reveals interviewing performance to be often mediocre. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of fluoro substitution on the fragmentation of the K‐shell excited/ionized pyridine studied by electron impact
Authors: Sakai Masamichi , Okada Kazumasa
Published: July 2011

Fragmentation of the pyridine ring followed by K‐shell excitation/ionization has been studied with 2‐fluoropyridine (2FPy) by electron impact. Ab initio molecular orbital (MO) calculations were also carried out to investigate the electronic states correlating with specific fragment ions. The fragment ions are produced characteristically at the N 1s edge, while the spectra observed at the F 1s and C 1s edges exhibit a small difference from that at the valence ionization. The production of the C4H2+, C4H3+ and C4H2F+ ions indicates that the cleavage of the NC6 and C2C3 bonds or the NC2 and C5C6 bonds is likely to occur after the N 1s excitation/ionization. Ab initio MO calculations indicate that the former fission is likely to proceed through the nN1π21π32 and nN0π22π32 excited states of the parent molecular dication. On the other hand, the breakage of the NC2 and C4C5 bonds, which specifically proceeds at the N 1s edge for 2‐methylpyridine, does not occur for 2FPy. The present calculation reveals that the products of this channel are unstable by the electronegativity of fluorine and that the relative energy of the Auger‐final states of 2FPy is lowered by the reorganization and electron correlation effects. Copyright © 2011 John Wiley & Sons, Ltd.
Application of MALDI TOF/TOF mass spectrometry and collision‐induced dissociation for the identification of disulfide‐bonded peptides
Authors: Janecki Dariusz J. , Nemeth Jennifer F.
Published: July 2011

This paper describes a method for the fast identification and composition of disulfide‐bonded peptides. A unique fragmentation signature of inter‐disulfide‐bonded peptides is detected using matrix‐assisted laser desorption/ionization (MALDI) time‐of‐flight (TOF)/TOF mass spectrometry and high‐energy collision‐induced dissociation (CID). This fragmentation pattern identifies peptides with an interconnected disulfide bond and provides information regarding the composition of the peptides involved in the pairing. The distinctive signature produced using CID is a triplet of ions resulting from the cleavage of the disulfide bond to produce dehydroalanine, cysteine or thiocysteine product ions. This method is not applicable to intra‐peptide disulfide bonds, as the cleavage mechanism is not the same and a triplet pattern is not observed. This method has been successfully applied to identifying disulfide‐bonded peptides in a number of control digestions, as well as study samples where disulfide bond networks were postulated and/or unknown. Copyright © 2011 John Wiley & Sons, Ltd.
Endogenous erythropoietin from astrocyte protects the oligodendrocyte precursor cell against hypoxic and reoxygenation injury
Authors: Kato Shin , Aoyama Mineyoshi , Kakita Hiroki , Hida Hideki , Kato Ineko , Ito Tetsuya , Goto Tatenobu , Hussein Mohamed H. , Sawamoto Kazunobu , Togari Hajime , Asai Kiyofumi
Published: July 2011

The hypoxia‐responsive cytokine erythropoietin (EPO) provides neuroprotective effects in the damaged brain during ischemic events and neurodegenerative diseases. The purpose of the present study is to evaluate the EPO/EPO receptor (EPOR) endogenous system between astrocyte and oligodendrocyte precursor cell (OPC) under hypoxia. We report here elevated EPO mRNA levels and protein release in cultured astrocytes following hypoxic stimulation by quantitative RT‐PCR and ELISA. Furthermore, the EPOR gene expressions were detected in cultured OPCs as in astrocytes and microglias by quantitative RT‐PCR. Cell staining revealed the EPOR expression in OPC. To evaluate the protective effect of endogenous EPO from astrocyte to OPCs, EPO/EPOR signaling was blocked by EPO siRNA or EPOR siRNA gene silencing in in vitro study. The suppression of endogenous EPO production in astrocytes by EPO siRNA decreased the protection to OPCs against hypoxic stress. Furthermore, OPC with EPOR siRNA had less cell survival after hypoxic/reoxygenation injury. This suggested that EPO/EPOR signaling from astrocyte to OPC could prevent OPC damage under hypoxic/reoxygenation condition. Our present finding of an interaction between astrocytes and OPCs may lead to a new therapeutic approach to OPCs for use against cellular stress and injury. © 2011 Wiley‐Liss, Inc.
Additive effects of fatty acid mixtures on the levels and ratio of amyloid β40/42 peptides differ from the effects of individual fatty acids
Authors: Amtul Zareen , Uhrig Markus , Beyreuther Konrad
Published: July 2011

Several studies have shown the protective and/or deleterious effects of dietary enrichment of single fatty acids (FAs) in several animal and cell‐culture models of Alzheimer's disease (AD). However, potential interactions among dietary fatty acids are traditionally ignored. None of these studies has examined and compared the differential effects of FAs in combination, as well as alone, for their effects on amyloid β production or AD. Here we investigated the effects of omega‐9 (oleic acid) and omega‐6 (linoleic and arachidonic acids) fatty acids, either alone or combined, on Aβ production by APP‐695 and SP‐C99 transfected COS‐7 cells. Overall, our results are the first to demonstrate that mixtures of FAs alter the production of Aβ40 and Aβ42 peptides and consequently the Aβ40:42 ratio differently from individual FAs. Here we show that the effects of a single lipid on Aβ production are not attributed to that single FA alone. Rather, the overall lipid composition influences the specificity and level of the regulated intramembranous proteolysis of APP by the γ‐secretase complex. Our results reinforce the importance of studying composite lipids/nutrients rather than single lipids or nutrients. © 2011 Wiley‐Liss, Inc.
Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes
Authors: Alvarez Veronica M. , Rama Rao Kakulavarapu V. , Brahmbhatt Monica , Norenberg Michael D.
Published: July 2011

Hepatic encephalopathy (HE) is the major neurological complication occurring in patients with acute and chronic liver failure. Elevated levels of blood and brain ammonia are characteristic of HE, and astrocytes are the primary target of ammonia toxicity. In addition to ammonia, recent studies suggest that inflammation and associated cytokines (CKs) also contribute to the pathogenesis of HE. It was previously established that ammonia induces the mitochondrial permeability transition (mPT) in cultured astrocytes. As CKs have been shown to cause mitochondrial dysfunction in other conditions, we examined whether CKs induce the mPT in cultured astrocytes. Cultures treated with tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, and interferon‐γ, individually or in a mixture, resulted in the induction of the mPT in a time‐dependent manner. Simultaneous treatment of cultures with a mixture of CKs and ammonia showed a marked additive effect on the mPT. As oxidative stress (OS) is known to induce the mPT, so we examined the effect of CKs and ammonia on hemeoxygenase‐1 (HO‐1) protein expression, a marker of OS. Such treatment displayed a synergistic effect in the upregulation of HO‐1. Antioxidants significantly blocked the additive effects on the mPT by CKs and ammonia, suggesting that OS represents a major mechanism in the induction of the mPT. Treatment of cultures with minocycline, an antiinflammatory agent, which is known to inhibit OS, also diminished the additive effects on the mPT caused by CKs and ammonia. Induction of the mPT in astrocytes appears to represent a major pathogenetic factor in HE, in which CKs and ammonia are critically involved. © 2011 Wiley‐Liss, Inc.
The (−1486T/C) promoter polymorphism of the TLR‐9 gene is associated with end‐stage knee osteoarthritis in a Chinese population
Authors: Su Sui‐Lung , Yang Hsin‐Yi , Lee Chian‐Her , Huang Guo‐Shu , Salter Donald M. , Lee Herng‐Sheng
Published: July 2011

Based on the recent observation that Toll‐like receptors (TLRs) may be involved in the pathogenesis of osteoarthritis (OA) we explored the possibility that human TLR gene polymorphisms are associated with OA. Two separate populations were studied in a two‐stage case–control study with a total of 503 OA patients and 428 healthy controls. The TLR‐2, TLR‐4, and TLR‐9 genotypes were assessed by real‐time polymerase chain reaction. Our data demonstrated a lack of association among TLR‐2, TLR‐4, and TLR‐9 (T‐1237C) polymorphisms and the risk of developing OA in both stages of the study. T‐1486C was significantly associated with OA in both populations with G1635A of TLR‐9 gene was found to be significantly associated with OA when the two populations were combined. Stratifying the samples by K‐L score there were significant differences in the genotype of the TLR‐9 T‐1486C and G1635A between OA of the knee grade 4 and controls. In haplotype analyses, the haplotype TTG and TTA revealed higher risk of OA and TCA confers a lower risk of OA in combined population. The present results demonstrate that TLR‐9 polymorphisms, in particular T‐1486C is significantly associated with OA. TLR‐9 gene polymorphisms may play a role in the etiology of knee OA. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:9–14, 2012
Hyperactivation of mTOR critically regulates abnormal osteoclastogenesis in neurofibromatosis type 1
Authors: Ma Junrong , Li Mi , Hock Janet , Yu Xijie
Published: July 2011

Individuals with nerofibromatosis Type 1 (NF1) frequently suffer a spectrum of bone pathologies, such as abnormal skeletal development (scoliosis, congenital bowing, and congenital pseudoarthroses, etc), lower bone mineral density with increased fracture risk. These skeletal problems may result, in part, from abnormal osteoclastogenesis. Enhanced RAS/PI3K activity has been reported to contribute to abnormal osteoclastogenesis in Nf1 heterozygous (Nf1+/−) mice. However, the specific downstream pathways linked to NF1 abnormal osteoclastogenesis have not been defined. Our aim was to determine whether mammalian target of rapamycin (mTOR) was a key effector responsible for abnormal osteoclastogenesis in NF1. Primary osteoclast‐like cells (OCLs) were cultured from Nf1 wild‐type (Nf1+/+) and Nf1+/− mice. Compared to Nf1+/+ controls, there were 20% more OCLs induced from Nf1+/− mice. Nf1+/− OCLs were larger and contained more nuclei. Hyperactive mTOR signaling was detected in Nf1+/− OCLs. Inhibition of mTOR signaling by rapamycin in Nf1+/− OCLs abrogated abnormalities in cellular size and number. Moreover, we found that hyperactive mTOR signaling induced abnormal osteoclastogenesis major through hyper‐proliferation. Our research suggests that neurofibromin directly regulates osteoclastogenesis through mTOR signaling pathway. Inhibiting mTOR may represent a viable strategy to treat NF1 bone diseases. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:144–152, 2012
Arsenic contamination in sesame and possible mitigation through organic interventions in the lower Gangetic Plain of West Bengal, India
Authors: Sinha Bishwajit , Bhattacharyya Kallol , Giri Pradip K , Sarkar Supradip
Published: July 2011

BACKGROUND: The widespread geogenic arsenic contamination of groundwater in the Gangetic Delta of West Bengal, leading to toxicities through the food chain—principally through irrigated rice—drew due attention from researchers. Oilseeds such as sesame might be a remunerative alternative to rice and can be grown with small quantities of contaminated groundwater.

RESULTS: The present study was conducted to explore the efficiency of organic matter in reducing arsenic accumulation in sesame. Accumulation of total arsenic in sesame seed and available arsenic in post‐harvest soils varied from 0.08 to 0.58 mg kg−1 and from 3.87 to 8.89 kg ha−1, respectively. The organic manures added as soil amendment significantly reduced the accumulation (concentration) of arsenic in sesame seed to a maximum extent of 65.5% (vermicompost), 50% (phosphocompost), 42% (mustard cake) and 40% (farmyard manure (FYM)) compared with the control counterpart. The risk associated with dietary exposure to arsenic‐contaminated sesame oil reached a value of 15.55% of provisional tolerable weekly intake for arsenic at the maximum accumulation of arsenic in sesame oil.

CONCLUSION: Substantial accumulation of arsenic in the soil–plant system was found. Risks of exposure to arsenic‐contaminated oil remained considerably high. Irrigation through surface water and organic amendments both significantly reduced arsenic accumulation in sesame. Copyright © 2011 Society of Chemical Industry
Supercritical CO2 extraction of oleoresin from marigold (Tagetes erecta L.) flowers and determination of its antioxidant components with online HPLC‐ABTS•+ assay
Authors: Gong Ying , Plander Szabina , Xu Honggao , Simandi Bela , Gao Yanxiang
Published: July 2011

BACKGROUND: Marigold is a traditional medicine herb which shows good pharmacological activity in many aspects. It is very important to obtain and investigate the specific bioactive compounds from marigold. The objective of the study was to extract the oleoresin from marigold with supercritical CO2 (SC‐CO2) at different pressures and temperatures, detect the fatty acid composition by gas chromatography–mass spectrometry and investigate the antioxidative components in the extracts by combined online high‐performance liquid chromatography‐2,2‐azinobis‐(3‐ethylbenzothiazolin‐6‐sulfonic acid (HPLC‐ABTS•+) post‐column assay and HPLC‐tandem mass spectrometry.

RESULTS: For the pressure range (20–40 MPa) and temperature range (30–70 °C), 30 MPa/70 °C gave the highest yield of oleoresin (58.9 g kg−1). The dominant fatty acids of marigold flower oleoresin were linoleic acid (>26.41%), palmitic acid (>24.22%) and oleinic acid (>20.12%). Significant effects of the extraction pressure and temperature on the antioxidant activity were observed (P < 0.05). Lutein esters, α‐tocopherol, β‐tocopherol, γ‐tocopherol and δ‐tocopherol were the dominant antioxidant compounds in the extracts.

CONCLUSION: The study has shown that the yield and total antioxidant activity of the marigold extracts were affected by the pressure and temperature of SC‐CO2, and that online HPLC technique could be used as an efficient and rapid method for separation and identification of bioactive compounds from a complex mixture. Copyright © 2011 Society of Chemical Industry
Effect of breed on performance and meat quality of first parity sows in a seasonal organic rearing system
Authors: Kongsted Anne G , Claudi‐Magnussen Chris , Hermansen John E , Horsted Klaus , Andersen Bent H
Published: July 2011

BACKGROUND: The objective was to compare the performance and meat quality of two different pig breeds: the modern crossbred Landrace × Yorkshire (LY) and the traditional Danish Black‐Spotted (BS) breed. The LY gilts and four of the BS gilts were inseminated with semen from Duroc (D) boars; the remaining BS gilts were served by BS boars. The experiment was performed on 26 gilts over 2 years.

RESULTS: The BS breed in general had smaller litter sizes and weaned on average in terms of kg piglet 35% less than the modern breed combination. Crossbred piglets of BS × D had growth rates from birth to weaning comparable with piglets of LY × D. BS first parity sows were significantly fatter and less meaty, and the meat was significantly redder and darker compared to LY. The sensory profiling revealed increased sweetness, crumbliness and tenderness in BS. Further, the fat of the BS breed seemed to be characterized by a special nutty taste.

CONCLUSION: The traditional breed has lower productivity and thereby higher costs of production compared to the modern genotypes. On the other hand, the meat and fat of the traditional purebred have special characteristics that might trigger a market premium. Copyright © 2011 Society of Chemical Industry
The use of high‐performance liquid chromatography to detect ochratoxin A in dried figs from the Spanish market
Authors: Pavón Miguel Ángel , González Isabel , de la Cruz Silvia , Martín Rosario , Lacarra Teresa García
Published: July 2011

BACKGROUND: Detection and quantification of ochratoxin A (OTA) in dried fig samples purchased in Spain has been carried out using high‐performance liquid chromatography with fluorescence detection after extraction with methanol and sodium bicarbonate, and clean‐up by using an immunoaffinity column.

RESULTS: The detection limit of the method was 0.06 ng g−1, and the limit of quantification 0.18 ng g−1. OTA was detected in 31 (88.6%) out of 35 samples of dried figs analysed, with concentrations that ranged from < 0.1 to 277 ng g−1. However, only three samples contained OTA concentrations above the tolerable level set by European Commission regulations for dried vine fruits (10 ng g−1).

CONCLUSION: The results of this survey show the value of monitoring OTA in dried figs especially if they are home grown. Copyright © 2011 Society of Chemical Industry
Benefits of β‐xylanase for wheat biomass conversion to bioethanol
Authors: Juodeikiene Grazina , Basinskiene Loreta , Vidmantiene Daiva , Makaravicius Tomas , Bartkiene Elena
Published: July 2011

BACKGROUND: The efficiency of bioethanol production from wheat biomass is related to the quality of end products as well as to safety criteria of co‐products such as distiller's dried grains with solubles (DDGS). The inclusion of a new biocatalyst for non‐starch polysaccharide degradation in fermentation processes could be one of the solutions. The objective of this study was to evaluate the influence of β‐xylanases in combination with traditional amylolytic enzymes on the efficiency of bioethanol production and DON detoxification during fermentation of Fusarium‐contaminated wheat biomass with high concentration of deoxynivalenol (DON; 3.95 mg kg−1).

RESULTS: The results showed that the negative effect of Fusarium spp. on yield and quality of bioethanol could be eliminated by the application of Trichoderma reesei xylanase in combination with amylolytic enzymes. This technological solution allowed to increase the concentration of ethanol in the fermented wort by 35.3% and to improve the quality of bioethanol by decreasing the concentrations of methanol, methyl acetate, isoamyl and isobutyl alcohols. Mass balance calculations showed that DDGS was the main source of DON contamination, comprising 74% of toxin found in wheat biomass. By using new enzyme combination for wheat biomass saccharification, a higher level of detoxification (41%) of DON was achieved during the fermentation process.

CONCLUSION: The addition of Trichoderma reesei xylanase played a positive role in bioethanol production from Fusarium‐contaminated wheat biomass, indicating that the yeast‐growing medium was enriched during the enzymatic treatment. Copyright © 2011 Society of Chemical Industry
Als Werkzeug voll etabliert
Authors: Richer Thomas
Published: July 2011

Fraglos beherrscht der Laser heute die Druckvorstufe als Produktionsmittel. Er hat zusammen mit der Digitalisierung und der Automatisierung das Herstellen der Druckformen in den letzten 15 Jahren revolutioniert. Der Beitrag gibt einen Überblick über die Rahmenbedingungen für die Erfolgsgeschichte des Lasers, über die eingesetzten Verfahren und aktuellen Entwicklungen sowie über zukünftige Trends und Anforderungen.
Drei in einem Kopf
Authors: Petring Dirk , Schneider Frank , Dickler Harald
Published: July 2011

Bei der Herstellung von Blechbaugruppen lassen sich durch die Integration von mehreren Laserverfahren in einer Maschine unproduktive Nebenzeiten senken und die produzierbare Variantenvielfalt erhöhen. Ein Laserkombikopf, der schneiden, messen und schweißen kann, macht dies möglich. Denn was man nicht im Kopf hat …
Qualitätssicherung bei Laserschweißprozessen
Authors: Blug Andreas
Published: July 2011

Eine CNN‐basierte Kamera ermöglicht so hohe Bildraten und kurze Latenzzeiten, dass innerhalb der Reaktionszeit des Schweißprozesses eine statistische Analyse durchgeführt und die Laserleistung entsprechend angepasst werden kann. Auf diese Weise gelang es erstmals, die Einschweißtiefe in das Unterblech zu regeln. Dies ermöglicht einerseits Schweißnähte im Sichtbereich und es verringert andererseits die Korrosion bei verzinkten Stahlblechen.
Der Röntgenblick ins Innerste des Prozesses
Authors: Abt Felix
Published: July 2011

Am Institut für Strahlwerkzeuge der Universität Stuttgart wurde eine Röntgenanlage in Betrieb genommen mit der es erstmals in Europa möglich ist, laserbasierte Fertigungsverfahren, wie das Laserschweißen, mit hoher örtlicher und zeitlicher Auflösung in ihrem Innersten zu beobachten. Mit dieser Technologie ist es nun möglich, die Abläufe der Laserbearbeitungsprozesse direkt zu analysieren, was unschätzbare Vorteile gegenüber der Prozessdiagnostik mit konventionellen Kameras bietet.
Comparison of the 2-step tuberculin skin test and the quantiFERON-TB gold in-tube test for the screening of tuberculosis infection before liver transplantation
Authors: Casas Susana , Muñoz Laura , Moure Raquel , Castellote Jose , Guerra Maria R. , Gonzalez Lucia , Andreu Ana , Rafecas Antoni G. , Alcaide Fernando , Santin Miguel
Published: July 2011

The ability of interferon-γ release assays (IGRAs) to detect latent tuberculosis (TB) infection before liver transplantation (LT) is not well established. The aims of this study were (1) to compare the ability of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-IT) test (a whole-blood IGRA) to diagnose latent TB infections in patients awaiting LT and (2) to correlate the results with the severity of liver disease. We conducted a prospective, cross-sectional study of patients who were evaluated for LT between July 2008 and July 2010. The 95 patients who were included underwent the 2-step TST and the QFT-IT test. The mean Model for End-Stage Liver Disease (MELD) score was 13.8. Forty-four patients (46.3%) had positive TST results, 42 (44.2%) had positive QFT-IT results, and 2 (2.1%) had indeterminate QFT-IT results. Simultaneous TST and QFT-IT testing yielded a positivity rate of 55.8% [95% confidence interval (CI) = 45.3-65.9] with either test, and the 2-step TST yielded a positivity rate of 46.3% (95% CI = 36.1-56.8); the difference was 9.5% (P = 0.004). In an adjusted analysis, the rates for positive TST results were lower in patients with MELD scores ≥18 [odds ratio (OR) = 0.2, 95% CI = 0.04-0.7], lower in Child-Pugh-Turcotte (CPT) class C patients versus CPT class A patients (OR = 0.1, 95% CI = 0.02-0.6), and higher in males (OR = 6.4, 95% CI = 1.9-22.0). In contrast, only being male (OR = 3.5, 95% CI = 1.1-11.0) was associated with positive QFT-IT results; no association was found with the MELD score (OR = 0.8, 95% CI = 0.2-2.8) or the CPT class (OR = 0.3; 0.05-1.4). In conclusion, the QFT-IT test is better than the TST for detecting latent TB infection in patients with more advanced liver disease. Our results support the regular use of the QFT-IT test for screening patients with end-stage liver disease for latent TB infection before LT. Liver Transpl 17:1205–1211, 2011. © 2011 AASLD.
The failure of immunosuppression withdrawal: Patient benefit is not detectable, inducible, or reproducible
Authors: Porrett Paige , Shaked Abraham
Published: July 2011

Key Points

(1) Immunosuppression is responsible for excellent patient outcomes.

(2) Immunosuppression withdrawal fails in most patients.

(3) Patients who may benefit from immunosuppression withdrawal cannot currently be identified.

(4) No data suggest that immunosuppression withdrawal decreases patient morbidity (ie, nephrotoxicity).

(5) The minimization of immunosuppression instead of withdrawal may be adequate for improving patient outcomes.
Infections in immunocompromised hosts and organ transplant recipients: Essentials
Authors: Fishman Jay A.
Published: July 2011

Key Points

(1) Why do we need to know anything about these patients? Regardless of their specialties, physicians are increasingly confronted with the side effects of therapies that cause varying degrees of immunosuppression: chemotherapy and stem cell transplantation for cancer, solid organ transplantation, and therapies for autoimmune and rheumatological diseases. The management of these patients is increasingly being returned to community-based physicians. The infectious disease clinician is faced with major challenges.

(2) The possible etiologies of infections are diverse; they range from common bacterial and viral pathogens that affect the entire community to opportunistic pathogens that are clinically significant only for immunocompromised hosts.

(3) Inflammatory responses are impaired by immunosuppressive therapy, and this results in diminished clinical and radiological findings. Thus, an early diagnosis is much more difficult, but it is the key to successful therapy. Invasive diagnostic procedures are often required.

(4) Antimicrobial therapies are often more complex in these patients versus other patients because of the urgency of empiric therapy and the frequency of drug toxicity and drug interactions.

(5) Drug interactions and drug toxicity are common. The initiation or cessation of antimicrobial therapies may alter the levels of calcineurin inhibitors, antifungal agents, and other drugs.

(6) Graft rejection and graft-versus-host disease may be confused with infections.

(7) New pathogens and new manifestations of infections in compromised hosts are also problems:
Polyester/Poly(meth)acrylate Block Copolymers by Combined Polycondensation/ATRP: Characterization and Properties
Authors: Chatterjee Uma , Wang Xiaojiang , Jewrajka Suresh K. , Soucek Mark D.
Published: July 2011

Polyester/poly(meth)acrylate block copolymers are synthesized using a combination of polycondensation and ATRP. All block copolymers are characterized by means of NMR and GPC. Agreement between theoretical molecular weights of the polymers with observed GPC values suggests controlled polymerization. In the case of unsaturated‐polyester‐based block copolymers the main chain double bond in the polyester backbone remains almost unaffected during ATRP. The unsaturated block copolymers are crosslinkable and can form networks upon photoirradiation in the presence of a suitable photoinitiator. These copolymers might be interesting candidates for coatings with better overall properties than those based on neat polyesters.

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