bluuebunny/crossref_metadata_2025 huggingface dataset:
Aging alters the expression of neurotransmission‐regulating proteins in the hippocampal synaptoproteome
Authors: VanGuilder Heather D. , Yan Han , Farley Julie A. , Sonntag William E. , Freeman Willard M.
Published: March 2010

J. Neurochem. (2010) 113, 1577–1588.

Decreased cognitive performance reduces independence and quality of life for aging individuals. Healthy brain aging does not involve significant neuronal loss, but little is known about the effects of aging at synaptic terminals. Age‐related cognitive decline likely reflects the manifestation of dysregulated synaptic function and ineffective neurotransmission. In this study, hippocampal synaptosomes were enriched from young‐adult (3 months), adult (12 months), and aged (26 months) Fischer 344 × Brown Norway rats, and quantitative alterations in the synaptoproteome were examined by 2‐DIGE and MS/MS. Bioinformatic analysis of differentially expressed proteins identified a significant effect of aging on a network of neurotransmission‐regulating proteins. Specifically, altered expression of DNM1, HPCA, PSD95, SNAP25, STX1, SYN1, SYN2, SYP, and VAMP2 was confirmed by immunoblotting. 14–3–3 isoforms identified in the proteomic analysis were also confirmed as a result of their implication in the regulation of the synaptic vesicle cycle and neurotransmission modulation. The findings of this study demonstrate a coordinated down‐regulation of neurotransmission‐regulating proteins that suggests an age‐based deterioration of hippocampal neurotransmission occurring between adulthood and advanced age. Altered synaptic protein expression may decrease stimulus‐induced neurotransmission and vesicle replenishment during prolonged or intense stimulation, which are necessary for learning and the formation and perseverance of memory.
Dopamine D2receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse
Authors: Oien Derek B. , Ortiz Andrea N. , Rittel Alexander G. , Dobrowsky Rick T. , Johnson Michael A. , Levant Beth , Fowler Stephen C. , Moskovitz Jackob
Published: March 2010

J. Neurochem.(2010)114, 51–61.

Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio‐behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2‐receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D2‐receptor were higher in knockout mice compared with wild‐type. However, the binding of dopamine D2‐receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D2‐receptors to G‐proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre‐synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D2‐receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild‐type mice. Involvement of specific methionine residue oxidation in the dopamine D2‐receptor third intracellular loop is suggested byin vitrostudies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D2‐receptor physiology and may be related to symptoms associated with neurological disorders and diseases.
The exceptional properties of 9‐methyl‐β‐carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti‐inflammatory effects
Authors: Polanski Witold , Enzensperger Christoph , Reichmann Heinz , Gille Gabriele
Published: March 2010

J. Neurochem.(2010)113, 1659–1675.

β‐Carbolines (BCs) are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson’s disease. However, we recently demonstrated protective and stimulatory effects of 9‐methyl‐BC (9‐me‐BC) in primary dopaminergic culture. In the present study, treatment with 9‐me‐BC unmasked a unique tetrad of effects. First, tyrosine hydroxylase (TH) expression was stimulated in pre‐existing dopa decarboxylase immunoreactive neurons and several TH‐relevant transcription factors (Gata2, Gata3, Creb1, Crebbp) were up‐regulated. Neurite outgrowth of TH immunoreactive (THir) neurons was likewise stimulated. The interaction with tyrosine kinases (protein kinase A and C, epidermal growth factor‐receptor, fibroblast growth factor‐receptor and neural cell adhesion molecule) turned out to be decisive for these observed effects. Second, 9‐me‐BC protected in acute toxicity models THir neurons against lipopolysaccharide and 2,9‐dime‐BC+toxicity. Third, in a chronic toxicity model when cells were treated with 9‐me‐BC after chronic rotenone administration, a pronounced regeneration of THir neurons was observed. Fourth, 9‐me‐BC inhibited the proliferation of microglia induced by toxin treatment and installed an anti‐inflammatory environment by decreasing the expression of inflammatory cytokines and receptors. Finally, 9‐me‐BC lowered the content of α‐synuclein protein in the cultures. The presented results warrant the exploration of 9‐me‐BC as a novel potential anti‐parkinsonian medication, as 9‐me‐BC interferes with several known pathogenic factors in Parkinson’s disease as outlined above. Further investigations are currently under way.
HANNIBAL'S INVASION ROUTE: AN AGE‐OLD QUESTION REVISITED WITHIN A GEOARCHAEOLOGICAL AND PALAEOBOTANICAL CONTEXT
Authors: MAHANEY W. C. , TRICART P. , CARCAILLET C. , BLARQUEZ O. , ALI A. A. , ARGANT J. , BARENDREGT R. W. , KALM V.
Published: March 2010

The point of Hannibal's departure from New Carthage in Iberia, in 218 bc, and his subsequent march along the Mediterranean coast to the Pyrénées and on to the Rhône Basin, has been reconstructed by ancient historians with considerable accuracy. The latter 400‐km phase through the Alps, however, has been the subject of some controversy as to whether the Punic Army followed a southern versus a northern invasion route, or some intermediate variant. What is certain from the ancient texts is that Hannibal was trapped by Gallic tribes in a large defile—a gorge large enough to hold the entire army—along the approach to the high col of passage on to the Po River Plains of northern Italia. The entrapment involved an enfilade attack planned by an unknown Gallic commander, a military operation that nearly decimated the Punic Army. Previous arguments as to the location of the defile have hinged on inconclusive topographic, geological and geomorphic assessments. New data from palaeobotanical reconstruction of the northern approach route show the Gorges de la Bourne and the Gorge du Bréda, astride the Isère River, to have been forest covered during the invasion, which would have made the Gallic assault impossible. The existing evidence argues for a southern route, the approach through the narrow defile of the Combe de Queyras, with passage over the Col de la Traversette, as argued by Sir Gavin de Beer nearly a half century ago. Narrowing the approach route focuses on sites worth geoarchaeological exploration.
EXTRAPOLATION OF PURCHASING POWER PARITIES USING MULTIPLE BENCHMARKS AND AUXILIARY INFORMATION: A NEW APPROACH
Authors: Rao D. S. Prasada , Rambaldi Alicia , Doran Howard
Published: March 2010

The paper presents an econometric framework for the construction of a consistent panel of purchasing power parities (PPPs) which makes it possible to combine all the PPP benchmark data from various phases of the International Comparison Program with the data on national price movements in the form of implicit deflators from national accounts. The method improves upon the current practice used in the construction of the Penn World Tables (PWT), and similar tables produced by the World Bank which tend to be anchored on a selected benchmark. The econometric formulation is based on a regression model for the national price levels where the disturbances are assumed to be heteroskedastic and spatially correlated across countries. The regression model along with data on country specific price movements are combined using a state–space formulation and optimum predictions of PPPs are obtained. As a property of the method presented in the paper, we show that the resulting PPP predictions are weighted averages of extrapolations of PPPs from different benchmarks—thus the method provides a formal approach which has a simple intuitive interpretation. The smoothed PPP predictions (and standard errors) obtained through the state–space are produced for both ICP‐participating and non‐participating countries and non‐benchmark years. A complete tableau of PPPs for 141 countries spanning the period 1970 to 2005 is compiled using the method. Results for some selected countries are presented and the new series are compared and contrasted with the currently available PWT series. Extrapolated series for the remaining countries are available from the authors upon request.
Increased Disclosure Requirements and Corporate Governance Decisions: Evidence from Chief Financial Officers in the Pre‐ and Post–Sarbanes‐Oxley Periods
Authors: WANG XUE
Published: March 2010

I study how increased internal control disclosure requirements mandated by the Sarbanes‐Oxley Act (SOX) affect annual corporate governance decisions regarding CFOs. Using non‐CEO, non‐COO executive officers as a control group, I find that CFOs of firms with weak internal controls receive lower compensation and experience higher forced turnover rates after the passage of SOX. In contrast, CFOs of firms with strong internal controls receive higher compensation and do not experience significant changes in forced turnover rates. These results are consistent with the “disclosure of type” hypothesis, which suggests that the mandatory internal control disclosures under SOX are a credible mechanism that effectively distinguishes good CFOs from bad ones by revealing the firm's internal control quality. The empirical evidence thus supports the notion that mandated increases in disclosure reduce information asymmetry in the executive labor market.
The Regulation of Public Company Auditing: Evidence from the Transition to AS5
Authors: DOOGAR RAJIB , SIVADASAN PADMAKUMAR , SOLOMON IRA
Published: March 2010

The replacement of Auditing Standard No. 2 (AS2) by Auditing Standard No. 5 (AS5) creates a natural experiment that sheds light on (1) potential inefficiencies caused by regulatory responses to a political crisis and (2) audit efficiency and effectiveness improvements resulting from the risk‐based approach embodied in AS5. We study these effects by examining the impact of AS5 on audit fees. We find that AS5 audit fees are aligned with auditee fraud risk, but not AS2 audit fees. Second, relative to AS2 benchmark levels, AS5 audit fees are, on average, lower for all auditees. Third, relative to AS2 benchmarks, AS5 fees are lower for lower‐fraud‐risk auditees but greater for higher‐fraud‐risk auditees. Overall, the evidence is consistent with (1) initial overregulation (via AS2) followed by reform (via AS5) and (2) auditors deploying a risk‐based audit approach to obtain both efficiency and potential effectiveness gains in audit production.
Cannabinoid CB1receptor‐interacting proteins: novel targets for central nervous system drug discovery?
Authors: Smith Tricia H , Sim‐Selley Laura J , Selley Dana E
Published: March 2010

The main pharmacological effects of marijuana, as well as synthetic and endogenous cannabinoids, are mediated through G‐protein‐coupled receptors (GPCRs), including CB1and CB2receptors. The CB1receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain, spasticity, neurodegenerative diseases and mood and substance abuse disorders. Evidence has accumulated to suggest that CB1receptors, like other GPCRs, interact with and are regulated by several other proteins beyond the established role of heterotrimeric G‐proteins. These proteins, which include the GPCR kinases, β‐arrestins, GPCR‐associated sorting proteins, factor associated with neutral sphingomyelinase, other GPCRs (heterodimerization) and the novel cannabinoid receptor‐interacting proteins: CRIP1a/b, are thought to play important roles in the regulation of intracellular trafficking, desensitization, down‐regulation, signal transduction and constitutive activity of CB1receptors. This review examines CB1receptor‐interacting proteins, including heterotrimeric G‐proteins, but with particular emphasis on non‐G‐protein entities, that might comprise the CB1receptosomal complex. The evidence for direct interaction with CB1receptors and potential functional roles of these interacting proteins is discussed, as are future directions and challenges in this field with an emphasis on the possibility of eventually targeting these proteins for drug discovery.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Oral sildenafil increases skin hyperaemia induced by iontophoresis of sodium nitroprusside in healthy volunteers
Authors: Blaise S , Hellmann M , Roustit M , Isnard S , Cracowski JL
Published: March 2010

Background and purpose:  Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated.

Experimental approach:  Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream.

Key results:  Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP iontophoresis.

Conclusions and implications:  Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension.
9,10‐Dihydro‐2,5‐dimethoxyphenanthrene‐1,7‐diol, from Eulophia ochreata, inhibits inflammatory signalling mediated by Toll‐like receptors
Authors: Datla Praneel , Kalluri Mani Deepthi , Basha Khalander , Bellary Akshaya , Kshirsagar Rajendra , Kanekar Yogesh , Upadhyay Shakti , Singh Shiva , Rajagopal Vikram
Published: March 2010

Background and purpose:  9,10‐Dihydro‐2,5‐dimethoxyphenanthrene‐1,7‐diol (RSCL‐0520) is a phenanthrene isolated from Eulophia ochreata, one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti‐inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti‐inflammatory properties of RSCL‐0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll‐like receptors (TLRs).

Experimental approach:  The in vitro anti‐inflammatory activities of RSCL‐0520 were investigated in LPS‐stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor‐κB (NF‐κB). Tumour necrosis factor (TNF)‐α levels in serum following LPS stimulation in mice and carrageenan‐induced paw oedema in rats were used as in vivo models.

Key results:  Pretreatment with RSCL‐0520 effectively inhibited LPS‐induced, TLR4‐mediated, NF‐κB‐activated inflammatory genes in vitro, and reduced both LPS‐induced TNF‐α release and carrageenan‐induced paw oedema in rats. Treatment with RSCL‐0520 reduced LPS‐stimulated mRNA expression of TNF‐α, COX‐2, intercellular adhesion molecule‐1, interleukin (IL)‐8 and IL‐1β, all regulated through NF‐κB activation. RSCL‐0520, however, did not interfere with any cellular processes in the absence of LPS.

Conclusions and implications:  RSCL‐0520 blocked signals generated by TLR4 activation, as shown by down‐regulation of NF‐κB‐regulated inflammatory cytokines. The inhibitory effect involved both MyD88‐dependent and ‐independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant‐derived TLR antagonists, as potential anti inflammatory agents.
Transplacental transfer of remifentanil in the pregnant ewe
Authors: Coonen JB , Marcus MAE , Joosten EAJ , van Kleef M , Neef C , van Aken H , Gogarten W
Published: March 2010

Background and purpose:  While remifentanil can be used either during labour or fetal surgery, more should be known about the transplacental transfer of this opioid. The aim of this study was to investigate the placental transfer and haemodynamic effects of remifentanil after i.v. administration to pregnant ewes.

Experimental approach:  Seven pregnant ewes received a continuous infusion of remifentanil (0.33 µg·kg−1·min−1) for 1 h, and maternal and fetal arterial blood samples were drawn at regular intervals during and up to 1 h after the discontinuation of the infusion. Haemodynamic parameters were monitored continuously. Blood gas samples were drawn at baseline and once during the infusion.

Key results:  Peak maternal remifentanil plasma levels of 4.0 ± 0.9 ng·mL−1 (mean ± SD) and peak fetal plasma levels of 0.4 ± 0.3 ng·mL−1 were obtained. Remifentanil plasma levels dropped rapidly after the discontinuation of the infusion. The continuous infusion of remifentanil did not result in significant maternal or fetal haemodynamic changes.

Conclusions and implications:  Remifentanil rapidly passes through the placenta of pregnant ewes and although remifentanil concentrations stay significantly lower in the fetus compared with those in the mother, remifentanil can be detected in significant amounts in the fetus.
2,3′,4,4′,5′‐Pentamethoxy‐trans‐stilbene, a resveratrol derivative, inhibits colitis‐associated colorectal carcinogenesis in mice
Authors: Li Haitao , Wu William Ka Kei , Li Zhi Jie , Chan Kam Ming , Wong Clover Ching Man , Ye Cai Guo , Yu Le , Sung Joseph Jao Yiu , Cho Chi Hin , Wang Mingfu
Published: March 2010

Background and purpose:  Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3′,4,4′,5′‐pentamethoxy‐trans‐stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti‐proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis‐associated colon carcinogenesis.

Experimental approach:  Seven‐week‐old Balb/c mice were injected i.p. with 10 mg·kg−1 azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice.

Key results:  Intragastric administration of PMS (25, 50 mg·kg−1 body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg·kg−1 inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of β‐catenin and down‐regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of β‐catenin.

Conclusions and implications:  PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis‐associated colon cancer in humans.
Quantification of brain endocannabinoid levels: methods, interpretations and pitfalls
Authors: Buczynski Matthew W , Parsons Loren H
Published: March 2010

Endocannabinoids play an important role in a diverse range of neurophysiological processes including neural development, neuroimmune function, synaptic plasticity, pain, reward and affective state. This breadth of influence and evidence for altered endocannabinoid signalling in a variety of neuropathologies has fuelled interest in the accurate quantification of these lipids in brain tissue. Established methods for endocannabinoid quantification primarily employ solvent‐based lipid extraction with further sample purification by solid phase extraction. In recent years in vivo microdialysis methods have also been developed for endocannabinoid sampling from the brain interstitial space. However, considerable variability in estimates of endocannabinoid content has led to debate regarding the physiological range of concentrations present in various brain regions. This paper provides a critical review of factors that influence the quantification of brain endocannabinoid content as determined by lipid extraction from bulk tissue and by in vivo microdialysis. A variety of methodological issues are discussed including analytical approaches, endocannabinoid extraction and purification, post‐mortem changes in brain endocannabinoid content, cellular reactions to microdialysis probe implantation and caveats related to lipid sampling from the extracellular space. The application of these methods for estimating brain endocannabinoid content and the effects of endocannabinoid clearance inhibition are discussed. The benefits, limitations and pitfalls associated with each approach are emphasized, with an eye toward the appropriate interpretation of data gathered by each method.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Endocannabinoid signalling: has it got rhythm?
Authors: Vaughn Linda K , Denning Gerene , Stuhr Kara L , de Wit Harriet , Hill Matthew N , Hillard Cecilia J
Published: March 2010

Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. The daily and seasonal cycles of the relationship of the earth and sun profoundly affect the terrestrial environment. Terrestrial species have adapted to these cycles in many ways, most well studied are circadian rhythms and hibernation. The purpose of this review was to examine literature support for three hypotheses: (i) endocannabinoid signalling exhibits brain region‐specific circadian rhythms; (ii) endocannabinoid signalling modulates the rhythm of circadian processes in mammals; and (iii) changes in endocannabinoid signalling contribute to the state of hibernation. The results of two novel studies are presented. First, we report the results of a study of healthy humans demonstrating that plasma concentrations of the endocannabinoid,N‐arachidonylethanolamine (anandamide), exhibit a circadian rhythm. Concentrations of anandamide are threefold higher at wakening than immediately before sleep, a relationship that is dysregulated by sleep deprivation. Second, we investigated differences in endocannabinoids and congeners in plasma fromMarmota monaxobtained in the summer and during the torpor state of hibernation. We report that 2‐arachidonoylglycerol is below detection inM. monaxplasma and that concentrations of anandamide are not different. However, plasma concentrations of the anorexigenic lipid oleoylethanolamide were significantly lower in hibernation, while the concentrations of palmitoylethanolamide and 2‐oleoylglycerol were significantly greater in hibernation. We conclude that available data support a bidirectional relationship between endocannabinoid signalling and circadian processes, and investigation of the contribution of endocannabinoid signalling to the dramatic physiological changes that occur during hibernation is warranted.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Defining “adequate” pathogen reduction performance for transfused blood components
Authors: Goodrich Raymond P. , Custer Brian , Keil Shawn , Busch Michael
Published: March 2010

Pathogen reduction of labile blood products offers the opportunity to introduce to the blood banking community the same mechanism of protection that is employed for fractionated or pooled plasma products today—blood components that have been treated with methods to inactivate or reduce the infectivity of a variety of organisms that may contaminate donated blood and thus potentially transmit infection via transfusion. Due to the mechanisms of action, the methods employed in the plasma fractionation environment are not directly applicable to labile blood products. This article examines whether the same criteria of performance required for plasma derivatives (i.e., 6 log/mL reduction by multiple orthogonal methods) should be applied to the treatment of labile components and if not what criteria for performance might be sufficient. In conducting this analysis, we have considered what has been learned in the past several decades regarding the dynamics and infectivity of various pathogens and disease transmission by blood products, the introduction and progressive enhancement of testing methods based on serology and nucleic acid testing, and the performance characteristics for pathogen reduction technologies that are available today.
Incremental Value of Contrast Echocardiography in the Diagnosis of Atrial Myxoma
Authors: Hari Pawan , Mohamad Tamam , Kondur Ashok , Jahania Salik M. , Afonso Luis
Published: March 2010

Intracardiac myxomas have traditionally been divided into solid ovoid and soft papillary types based on a morphological appearance. Papillary myxomas given their friable nature are far more likely to cause embolic phenomenon and present with neurological symptoms, making it necessary to discriminate between these tumor subtypes. Papillary myxomas have also been demonstrated to be significantly less vascular than their ovoid counterparts in previous angiographic studies. We describe here for the first time, the application of transesophageal real time myocardial contrast echocardiography in a case of atrial papillary myxoma to assess tumor vascularity. (Echocardiography 2010;27:E46‐E49)
Microstructural Origin of Magnetic and Giant Dielectric Behavior of Sr2MnTiO6−δ Perovskite Nanocrystals
Authors: Álvarez‐Serrano Inmaculada , Arillo M. Ángeles , García‐Hernández Mar , López M. Luisa , Pico Carlos , Veiga M. Luisa
Published: March 2010

Polycrystalline Sr2MnTiO6−δ (SMTO) nanosized powders have been prepared by the liquid mix technique. Thermogravimetric experiments show the presence of small amounts (4%) of Mn3+ in the sample. A systematic structural study shows the stabilization of nanocrystals of about 50 nm, which crystallize in an space group Pm3m, i.e. the arystotype perovskite. Microstructural analysis permits us to interpret the electrical and magnetic properties in terms of a high degree of structural disorder including intergrowths. Although the existence of polytypes in small regions is observed, the title sample can be globally (macroscopically) considered as cubic. A spin‐glass type magnetic frustration behavior has been detected using different techniques: DC and AC magnetization variation with temperature and magnetic field. SMTO shows a very high dielectric constant, approaching 105 at 580 K, and being practically temperature independent above 680 K. Also, the dependence with frequency is negligible below 580 K. Electrical behavior has been interpreted considering the nanoscaled size of particles. The high semiconductive character of the sample perovskite is the key feature of the giant dielectric constant observed.
Nickel, cobalt and chromate sensitization and occupation*
Authors: Rui Francesca , Bovenzi Massimo , Prodi Andrea , Belloni Fortina Anna , Romano Ilaria , Peserico Andrea , Corradin Maria Teresa , Carrabba Enrico , Larese Filon Francesca
Published: March 2010

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis.

Objectives: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors.

Patients/Methods: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis.

Results: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26–35 years in comparison with the youngest group (15–25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16–2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00–2.49) and men (OR 2.24; 95% CI 1.55–3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09–2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18–2.93).

Conclusions: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.
Contact allergy to gold as a model for clinical‐experimental research
Authors: Möller Halvor
Published: March 2010

The high frequency of contact allergy to gold in patients with dermatitis was established after exhaustive skin testing, determining the right test agent, the best concentration, and repeated test readings. Metallic gold in contact with skin is slowly ionized, permitting absorption and haptenisation. Contact allergy to gold is statistically correlated to the presence of dental gold. But in many case reports it has also been attributed to wearing gold jewellery, albeit not statistically demonstrated. Epicutaneous testing with gold salts increases the blood gold level, and by intramuscular injection systemic contact dermatitis is provoked in an allergic individual. In coronary heart disease, gold‐coated intravascular stents have been shown to be correlated to contact allergy and even to an increased risk of restenosis. Gold is far from inert.
Melatonin: a novel neuroprotectant for the treatment of glaucoma
Authors: Belforte Nicolás A. , Moreno María C. , De Zavalía Nuria , Sande Pablo H. , Chianelli Mónica S. , Keller Sarmiento María I. , Rosenstein Ruth E.
Published: March 2010

Abstract: Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma‐aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L‐arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.
Spectroscopic Imaging of Breast Cancer
Authors: Sijens P. E. , Dorrius M. D.
Published: March 2010

Single voxel magnetic resonance spectroscopy (MRS) has been the standard in human breast tumour studies published to date. This method is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, frequently referred to as spectroscopic imaging, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal‐to‐noise ratio of the choline (Cho) signal serving as a measure of tumour activity. Demonstrated in this study is that in a standard clinical setting with a regular 1.5 T MR scanner, it is possible to perform quantitative multivoxel MRS. Using a pre‐measurement to map the distributions of water and fat, and literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumours, one can determine the concentrations of Cho in different tumour compartments and surrounding tissues in two brief multivoxel MRS measurements. Quantitative diagnostic and follow‐up studies of focal breast pathology are now possible.
Breast Magnetic Resonance Imaging as a Problem‐Solving Modality?
Authors: Dorrius M. D. , Pijnappel R. M. , Oudkerk M.
Published: March 2010

Mammography is the primary imaging modality for the early detection of breast cancer. Because of the low predictive value of mammography, a large majority of patient referred for biopsy have benign disease. The question is whether magnetic resonance imaging (MRI) is a diagnostic alternative to biopsy for women with inconclusive findings at mammography or mammographic (Breast Imaging Reporting And Data System (BIRADS) 3 lesions. In this article the breast MRI and indications will be described. An overview will be given of MRI as a problem‐solving modality in mammographic BIRADS 3 lesions and inconclusive mammographic findings with and without microcalcifications. The negative predictive value of breast MRI must be sufficiently high to definitively indicate a lack of need for biopsy and thus to be an effective addition to the work‐up of mammographic BIRADS 3 lesions or inconclusive findings on mammography. Therefore, breast MRI should only be used for cases with proven diagnostic value.
Conventional Tc‐99m‐based Bone Scan Versus Fluoride Positron Emission Tomography Combined with Computed Tomography in the Assessment of Bone Metastases in Prostate Cancer Patients
Authors: Beheshti M. , Pirich C. , Langsteger W.
Published: March 2010

In prostate cancer, bone metastasis is related to a poor prognosis and is one of the major causes of morbidity and mortality. Detection of metastatic bone disease is particularly important in prostate cancer patients with high probability for distant metastases before embarking on radical prostatectomy or radiation therapy. The choice of imaging modalities that best depict the metastatic bony lesions may vary depending on different patterns of bone metastases. Bone scintigraphy has been used routinely in the evaluation of prostate cancer patients in the last decades. However, it suffers from adequate specificity. Single photon emission tomography (SPECT) increases the sensitivity and specificity of planar bone scanning especially for the evaluation of the spine. Recently, positron emission tomography (PET) using F‐18 Fluoride shows promising results in the detection of bone metastases especially in cancers with prominent osteoblasic pattern of bone metastases such as prostate cancer. This article reviews the value of conventional planar bone scanning, SPECT, SPECT/CT as well as F‐18 Fluoride PET/CT in the assessment of bone metastases in prostate cancer patients.
The Role of F‐18 Choline PET and PET/CT in Prostate Cancer
Authors: Kohlfürst S. , Malle P. , Igerc I. , Gallowitsch H. J. , Lind P.
Published: March 2010

F‐18 fluorocholine [fluoromethyl‐dimethyl‐2‐hydroxyethyl‐ammonium (FCH)] is a choline analogue that shows great structural similarity to natural choline. The pathophysiological basis for the use of choline and its derivates for prostate cancer (PC) imaging are the elevation of choline levels and the up‐regulation of choline kinase activity in malignant cells. In order to allow rapid tumour growth, malignant cells are able to trap choline to produce phosphatidylcholine, part of the cellular membrane. As shown in recent studies, F‐18 choline PET and PET/CT might be a valuable tool in detecting the primary tumour in case of elevated prostate‐specific antigen (PSA) serum levels. However, data are not consistent, and further research is necessary before general recommendations concerning F‐18 choline PET and PET/CT can be given in this setting. Furthermore, some studies investigated the accuracy of F‐18 choline PET and PET/CT in detecting lymph node or bone metastases and local recurrences in case of PSA relapse in patients with a history of PC.
Proteomics Study of COI1‐regulated Proteins in Arabidopsis Flower
Authors: Chua Lingling , Shan Xiaoyi , Wang Junxia , Peng Wen , Zhang Guiyou , Xie Daoxin
Published: March 2010

Jasmonates (JAs) are a new class of plant hormone that regulate expression of diverse genes to mediate various plant responses. The Arabidopsis F‐box protein COI1 is required for plant defense and male fertility in JA signal pathway. To further investigate the regulatory role of COI1 in male fertility, we compared the proteomics profiles of Arabidopsis wild type (WT) flowers with coi1‐1 mutant male‐sterile flowers using two‐dimensional difference gel electrophoresis coupled with matrix‐assisted laser desoption/ionization‐time‐of‐flight mass spectrometry. Sixteen proteins with potential function in specific biological processes such as metabolism processes and defense/stress responses were differentially expressed in WT and coi1‐1 mutant flowers. Verification on a phi class glutathione transferase AtGSTF9, one out of these 16 identified proteins, revealed that the expression of AtGSTF9 was severely downregulated in flowers of coi1‐1 mutant compared with that of WT. Further function analyses of these genes would provide new insights into the molecular basis of COI1‐regulated male fertility.
Pharmacotherapy of cholestatic liver diseases
Authors: PAUMGARTNER Gustav
Published: March 2010

New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid‐induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6‐ethyl‐chenodeoxycholic acid and 24‐nor‐ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases.
Th17 cells: The emerging reciprocal partner of regulatory T cells in the liver
Authors: ZHAO Li , QIU De Kai , MA Xiong
Published: March 2010

T helper cells that produce interleukin‐17 (IL‐17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid‐related orphan nuclear receptor‐γt. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)‐β induces Treg‐specific transcription factor Forkhead box P3(FOXP3), while the addition of IL‐6 to TGF‐β inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL‐6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL‐2 and IL‐27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune‐related liver diseases.
Differential gene and protein expression in primary gastric carcinomas and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis
Authors: XIE Hai Long , LI Zhi Yu , GAN Run Liang , LI Xiao Jie , ZHANG Qing Li , HUI Mei , ZHOU Xiu Tian
Published: March 2010

OBJECTIVE:  To gain insight into the molecular events of lymph node metastasis of human gastric carcinoma.

METHODS:  The gene expression profile of five matched primary gastric carcinomas and their lymph node metastases was analyzed by complementary DNA (cDNA) microarray. Differential genes were identified in the metastatic and corresponding primary tumor pairs. Among the differentially expressed genes, carbonic anhydrase II (CAII) and insulin‐like growth factor binding protein 4 (IGFBP 4) genes were detected by RT‐PCR. CTTN protein expression was examined by tissue microarray.

RESULTS:  There was a high expression (over twofold) of 44 genes and a low expression (under twofold) of 32 genes in lymph node metastasis compared with primary gastric carcinoma, respectively. CAII mRNA was downregulated and IGFBP 4 mRNA was upregulated in paired lymph node metastases of gastric carcinomas. The overexpression of CTTN protein was related to the lymph node metastasis and the clinical stage of gastric carcinomas.

CONCLUSION:  This study showed that there is a low expression of genes relative to growth signal and immune response in lymph node metastases, and a high expression of genes relative to growth factor, cell cycle, cell motility and adhesion in lymph node metastases compared with primary gastric carcinomas. The expression of CTTN was related to the invasion and metastasis of gastric cancer.
Protecting Minority Shareholders: Listed versus Unlisted Firms
Authors: Loderer Claudio , Waelchli Urs
Published: March 2010

Listed firms have an incentive to render themselves attractive to investors at large. This paper examines whether listed and unlisted firms differ in their care for minority shareholders and finds supporting evidence. We examine control structure, disclosure, board architecture and processes, and director compensation. The corporate governance package in listed firms differs from that in unlisted firms in terms of levels and mix of the different provisions. The data also suggest that listed firms perform better.
Are Member Firms of Corporate Groups Less Risky?
Authors: Chen Carl R. , Guo Weiyu , Tay Nicholas S.P.
Published: March 2010

The evidence we uncover suggests that the practice of profit and risk sharing among keiretsu firms reduces the firm level idiosyncratic risk. However, rather than eliminating firm‐level risk, it is being transformed into market‐level risk. Since market‐level risk is priced, this actually destroys shareholders’ wealth. Additionally, the heightened correlation among keiretsu firms essentially diminishes the diversification efficacy of a portfolio of keiretsu firms. In summary, our results suggest that the practice of profit and risk sharing, which on the surface seems to be a blessing, may actually have a detrimental effect on the value of keiretsu firms.
Do Corporate Venture Capitalists Add Value to Start‐Up Firms? Evidence from IPOs and Acquisitions of VC‐Backed Companies
Authors: Ivanov Vladimir I. , Xie Fei
Published: March 2010

We present evidence that corporate venture capitalists (CVCs) add value to start‐up companies only when the start‐ups have a strategic fit with the parent corporations of CVCs. We find that CVCs provide a variety of services and support that suit the specific needs of start‐ups operating in different industries. CVC‐backed start‐ups are able to obtain higher valuations at the IPO than non‐CVC‐backed ones, and the value added by CVCs concentrates in start‐ups with a strategic overlap with CVC parents. Entrepreneurial companies with strategic CVC backing also receive higher takeover premiums when they become acquisition targets.
Intraday Behavior of Stock Prices and Trades around Insider Trading
Authors: Inci A. Can , Lu Biao , Seyhun H. Nejat
Published: March 2010

Our evidence indicates that insiders’ trades provide significant new information to market participants and they are incorporated more fully in stock prices as compared to noninsiders’ trades. We find that market professionals do not front‐run insiders’ trades. Both insiders’ purchases and sales result in significant contemporaneous and subsequent price impact, while sales by large shareholders result in a contemporaneous stock price decline that is subsequently reversed. The arrival of insider purchases reverse the prevailing negative order imbalances from third party trades and lead to piggy‐backing by market professionals resulting in subsequent market purchase orders as well as stock price increases.
Do Lead Banks Exploit Syndicate Participants? Evidence from Ex Post Risk
Authors: Panyagometh Kamphol , Roberts Gordon S.
Published: March 2010

Loan syndication involves a repeated game between lead banks and syndicate members. Lead banks do not use their private information to exploit syndicate participants but rather focus on accurately certifying loan quality. Using borrowers' financial ratios (shifts in Altman's Z scores) after origination to proxy for bank private information, we find that lead banks syndicate larger proportions of loans that subsequently do not experience lower Z scores. Performance pricing covenants under which borrowers commence to pay higher spreads if ratios (or credit ratings) deteriorate constitute a positive signal reducing agency costs and are associated with higher proportions of syndication.