bluuebunny/crossref_metadata_2025 huggingface dataset:
Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B‐cell lymphoma: Autopsy case
Authors: Yamada Sohsuke , Tanimoto Akihide , Matsuki Yasumasa , Hisada Yuji , Sasaguri Yasuyuki
Published: August 2009

A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B‐cell lymphoma (DLBCL) is reported herein. A 49‐year‐old Japanese man had undergone peritoneo‐venous shunt against refractory ascites due to hepatitis C virus‐positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon‐like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity.
Three energy‐based multiaxial HCF criteria for fatigue life determination in components under random non‐proportional stress fields
Authors: SHARIYAT M.
Published: August 2009

The prominent high cycle fatigue (HCF) criteria have been generally proposed based on definition of an equivalent stress that is mainly a modified version of a static failure criterion or a static yield function. One or more effects including the mean normal and shear stresses, different phase shifts or random frequencies of the stress components, relative instantaneous time variations of the stress components, relative time locations of the extrema of the time histories of the stress components, etc. have not been considered by many of the previously proposed criteria. In the present paper, based on the proposed instantaneous stress amplitude and mean stress concepts, three new energy‐based HCF criteria are proposed to overcome the mentioned shortcomings. A relevant fatigue life assessment algorithm is proposed and results of the prominent criteria are compared with results of the proposed criteria as well as the experimental results prepared by the author. To introduce a comprehensive study, the criteria are examined for components with complicated geometries under proportional, non‐proportional and random loadings. Results confirm the efficiency and accuracy of the proposed criteria. Furthermore, it is deduced that the Liu–Zenner type criteria which include the hydrostatic stress implicitly are more accurate than the Papadopoulos‐type criteria that consider the hydrostatic stress explicitly.
Are treelines advancing? A global meta‐analysis of treeline response to climate warming
Authors: Harsch Melanie A. , Hulme Philip E. , McGlone Matt S. , Duncan Richard P.
Published: August 2009

Treelines are temperature sensitive transition zones that are expected to respond to climate warming by advancing beyond their current position. Response to climate warming over the last century, however, has been mixed, with some treelines showing evidence of recruitment at higher altitudes and/or latitudes (advance) whereas others reveal no marked change in the upper limit of tree establishment. To explore this variation, we analysed a global dataset of 166 sites for which treeline dynamics had been recorded since 1900 AD. Advance was recorded at 52% of sites with only 1% reporting treeline recession. Treelines that experienced strong winter warming were more likely to have advanced, and treelines with a diffuse form were more likely to have advanced than those with an abrupt or krummholz form. Diffuse treelines may be more responsive to warming because they are more strongly growth limited, whereas other treeline forms may be subject to additional constraints.
Evaluation of the serum testosterone to prostate‐specific antigen ratio as a predictor of prostate cancer risk
Authors: Morote Juan , Planas Jacques , Ramirez Cristobal , Gómez Esther , Raventós Carles X. , Placer José , Catalán Roberto , De Torres Inés M.
Published: August 2009

Study Type – Diagnostic (exploratory cohort)  Level of Evidence 2b

OBJECTIVE

To analyse the ratio of serum testosterone (sT) to prostate‐specific antigen (PSA) as a predictor of prostate cancer risk, as low levels of sT have been related to a greater risk of prostate cancer, and its ratio with serum PSA level was recently proposed as a new tool to increase the specificity of PSA.

PATIENTS AND METHODS

In all, 439 consecutive men with a normal digital rectal examination and a serum PSA level of 4.1–20 ng/mL had a transrectal ultrasonography‐guided biopsy using a 10‐core scheme, with an additional 1–8 cores according to prostate volume and patient age. The sT level was determined before the procedure using a chemiluminescent assay, and the ratio of sT to PSA (sT/PSA) was calculated after transforming sT measurements from ng/dL to ng/mL. The percentage free PSA (%fPSA) and PSA density were also included in this analysis.

RESULTS

The overall cancer detection rate was 42.1%. The median sT level was 469 ng/dL in men with cancer and 499 ng/dL in those without (P = 0.521). The median sT/PSA was 0.68 and 0.74, respectively (P = 0.215). However, the median %fPSA was 14 in men with cancer and 17 in men without (P < 0.001) and the median PSA density was 0.22 and 0.16, respectively (P < 0.001). The multivariate analysis confirmed the independent predictive value only for %fPSA (odds ratio 0.94, 95% confidence interval 0.91–0.98) and PSA density (5.8, 3.42–19.8).

CONCLUSION

These results do not support the use of sT/PSA for predicting the risk of prostate cancer and to increase the specificity of PSA.
The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized disease
Authors: Porten Sima P. , Cooperberg Matthew R. , Carroll Peter R.
Published: August 2009

Study Type – Prognosis (case series)  Level of Evidence 4

OBJECTIVE

To determine if prostate tumour volume is an independent prognostic factor in a contemporary cohort of men who had a radical prostatectomy (RP) for clinically localized disease, as the effect of tumour volume on prostate cancer outcomes has not been consistently shown in the era of widespread screening with prostate‐specific antigen (PSA).

PATIENTS AND METHODS

The study included 856 men who had RP from 1998 to 2007 for localized prostate cancer. Tumour volume based on pathology was analysed as a continuous and categorized (<0.26, 0.26–0.50, 0.51–1.00, 1.01–2.00, 2.01–4.00, >4.00 mL) variable using Cox proportional hazards regression and Kaplan‐Meier analysis. A multivariable analysis was also conducted controlling for PSA level, Gleason grade, surgical margins, and pathological stage.

RESULTS

Tumour volume had a positive association with grade and stage, but did not correlate with biochemical recurrence‐free survival on univariate analysis as a continuous variable (hazard ratio 1.00, P = 0.09), and was only statistically significant for volumes of >4 mL as a categorical variable. No tumour volume was an independent predictor of prostate cancer recurrence on multivariate analysis. There was no difference between tumour volume and time to cancer recurrence for organ‐confined tumours using Kaplan‐Meier analysis. In low‐risk patients (PSA level <10 ng/mL, Gleason score ≤6, clinical stage T1c/T2a) tumour volume did not correlate with biochemical recurrence‐free survival in univariate or multivariable analysis.

CONCLUSIONS

There is no evidence that tumour volume is an independent predictor of prostate cancer outcome and it should not be considered as a marker of tumour risk, behaviour or prognosis.
Grounding as a facilitator in Anglo‐Canadian and Mainland Chinese conversations
Authors: Aguilera Laura , Li Han Z.
Published: August 2009

This study examined whether a short training in grounding strategies could improve intercultural communication. Forty intercultural dyads (Anglo‐Canadians and Mainland Chinese) were randomly assigned to experimental and control groups. Prior to their conversations the experimental groups received 10–15 min training on grounding while the control groups received no training. The trained dyads performed significantly better than the untrained dyads in grounding, speaker presentation and listener recall, thus documenting that the 10–15 min training on grounding was fruitful in improving intercultural communication. Grounding training may open a new avenue for reducing intercultural miscommunication, thus improving information transmission.
Interpersonal perceptions and metaperceptions of relationship closeness, satisfaction and popularity: A relational and directional analysis
Authors: Ho David Y. F. , Chau Albert W. L.
Published: August 2009

Relationship closeness, satisfaction in interaction, and popularity in mainland China was investigated using a methodological relational approach, which stresses the bidirectional nature of perceptions and metaperceptions. Two studies were conducted: one involving 164 dyads and the other 20 five‐member groups; participants were college students of both sexes who were well acquainted with one another. Major results are: (i) liking perceptions and metaperceptions are predominately relational in nature; (ii) assumed reciprocities are not consistently larger than actual reciprocities; and (iii) directional congruence is modest for closeness, but high for satisfaction and popularity. These results are discussed in terms of methodological relationalism, particularly the construct of directionality.
Perception of achievement attribution in individual and group contexts: Comparative analysis of Japanese, Korean, and Asian‐American results
Authors: Muramoto Yukiko , Yamaguchi Susumu , Kim Uichol
Published: August 2009

The present study focuses on the relational dynamics between individual and group attributions and examines cultural variations of people's perceptions of self‐enhancing and group‐enhancing attributions. Middle school students in Japan, Korea and the USA (Hawaii) were asked to read a vignette and to evaluate the stimulus person who makes an internal or external attribution for his personal or team's success. The results revealed that: (i) the self‐effacing attributor was perceived as likable by the participants from all three cultures, but as less self‐confident by Asian‐Americans; and (ii) although Japanese and Koreans share similar cultural backgrounds, they had different preferences for the group‐enhancing or group‐effacing attributions. The different systems of self‐enhancement across cultures are discussed.
Using the implicit association test across cultures: A case of implicit self‐esteem in Japan and Canada
Authors: Szeto Andrew C. H. , Sorrentino Richard M. , Yasunaga Satoru , Otsubo Yasunao , Kouhara Sadafusa , Sasayama Ikuo
Published: August 2009

Previous research has suggested that implicit self‐esteem might be universally positive. In the present study implicit self‐esteem, as measured by the implicit association test (IAT), was found to be positive in both Japanese and Canadian participants. However, contrary to prior research, Japanese participants were found to have significantly lower implicit self‐esteem than Canadians. Japanese participants also had lower scores on an exploratory measure of collective implicit self‐esteem. In general, the results of the present study point to the complexities in the study of implicit self‐esteem across cultures. Inconsistencies between the present and previous research might reflect divergent methodologies used in the IAT. The applicability of the IAT in a cross‐cultural setting is discussed.
Measuring subjective well‐being: A comparison of China and the USA
Authors: Zhang Jin , Yang Yu , Wang Hui
Published: August 2009

In this article the structure of subjective well‐being (SWB), the relationship between household income and SWB and mean differences in components of SWB in China and the USA are investigated. Both China and the USA were characterized in a three‐factor model of SWB (life satisfaction, positive affect and negative affect). Household income was more strongly positively correlated with the three major components of SWB in China than in the USA. Lower levels of SWB were generally reported by participants in China than in the USA; however, there were mean differences in different regions of China.
Do Differences in Financial Development Explain the Global Pattern of Current Account Imbalances?
Authors: Gruber Joseph , Kamin Steven
Published: August 2009

Building on the panel‐regression approach of Chinn and Prasad (2003) and Gruber and Kamin (2007), we assess whether differences in financial development can explain the large developing‐country surpluses or large US deficits. We find little evidence to support these hypotheses. We also assess whether differences in asset returns, an alternative measure of the attractiveness of financial assets, can explain the international pattern of capital flows. Lower bond yields have been generally associated with larger current account deficits in industrial countries. However, US bond yields have not been significantly lower than those in other industrial economies, suggesting that US financial assets have not been unusually attractive. We consider an alternative hypothesis that spending in the United States was uniquely responsive to lower costs of capital. However, we found this hypothesis also to be weak, as household saving rates have declined throughout the industrial economies.
Capital Flows, Capitalization, and Openness in Emerging East Asian Economies
Authors: Mandilaras Alex , Popper Helen
Published: August 2009

We examine the international capital flows of seven East Asian emerging economies over the last decade and a half. We find that domestic capital market conditions appear to be the best predictors of the changes in the total capital flows of these countries. Overall, changes in capital market openness are less helpful in explaining the behavior of the recent capital flows of these economies. Finally, we find that, while US macroeconomic conditions are strong predictors of GDP growth in the region, US conditions matter very little for the region's capital flows.
Monetary and Financial Integration in the EMU: Push or Pull?
Authors: Spiegel Mark M.
Published: August 2009

This paper examines the channels through which monetary union increased financial integration, using panel data on bilateral international commercial bank claims from 1998–2006. I decompose the increase in claims into three channels: a “borrower effect,” as a country's EMU membership may leave its borrowers more creditworthy in the eyes of foreign lenders; a “creditor effect,” as membership in a monetary union may increase the attractiveness of a nation's commercial banks as intermediaries, perhaps through increased scale economies or through an improved regulatory environment after the advent of monetary union; and a “pairwise effect,” as joint membership in a monetary union increases the quality of intermediation between borrowers and creditors when both are in the union. Isolating these three channels through a series of difference‐in‐differences specifications, I find that the pairwise effect is the primary source of increased financial integration. This result is robust to a number of sensitivity exercises.
Sterilization, Monetary Policy, and Global Financial Integration
Authors: Aizenman Joshua , Glick Reuven
Published: August 2009

This paper investigates the changing pattern and efficacy of sterilization within emerging market countries as they liberalize markets and integrate with the world economy. We estimate the marginal propensity to sterilize foreign asset accumulation associated with net balance of payments inflows, across countries, and over time. We find that the extent of sterilization of foreign reserve inflows has risen in recent years to varying degrees in Asia as well as in Latin America, consistent with greater concerns about the potential inflationary impact of reserve inflows. We also find that sterilization depends on the composition of balance of payments inflows.
Generalized Augmentation to Control the False Discovery Exceedance in Multiple Testing
Authors: FARCOMENI ALESSIO
Published: August 2009

Abstract.  A new multiple testing procedure, the generalized augmentation procedure (GAUGE), is introduced. The procedure is shown to control the false discovery exceedance and to be competitive in terms of power. It is also shown how to apply the idea of GAUGE to achieve control of other error measures. Extensions to dependence are discussed, together with a modification valid under arbitrary dependence. We present an application to an original study on prostate cancer and on a benchmark data set on colon cancer.
Empirical Likelihood Inference for the Cox Model with Time‐dependent Coefficients via Local Partial Likelihood
Authors: SUN YANQING , SUNDARAM RAJESHWARI , ZHAO YICHUAN
Published: August 2009

Abstract. The Cox model with time‐dependent coefficients has been studied by a number of authors recently. In this paper, we develop empirical likelihood (EL) pointwise confidence regions for the time‐dependent regression coefficients via local partial likelihood smoothing. The EL simultaneous confidence bands for a linear combination of the coefficients are also derived based on the strong approximation methods. The EL ratio is formulated through the local partial log‐likelihood for the regression coefficient functions. Our numerical studies indicate that the EL pointwise/simultaneous confidence regions/bands have satisfactory finite sample performances. Compared with the confidence regions derived directly based on the asymptotic normal distribution of the local constant estimator, the EL confidence regions are overall tighter and can better capture the curvature of the underlying regression coefficient functions. Two data sets, the gastric cancer data and the Mayo Clinic primary biliary cirrhosis data, are analysed using the proposed method.
Abacavir and risk of myocardial infarction in HIV‐infected patients on highly active antiretroviral therapy: a population‐based nationwide cohort study
Authors: Obel N , Farkas DK , Kronborg G , Larsen CS , Pedersen G , Riis A , Pedersen C , Gerstoft J , Sørensen HT
Published: August 2009

Objective

The aim of the study was to examine whether exposure to abacavir increases the risk for myocardial infarction (MI).

Design, setting and subjects

This was a prospective nationwide cohort study which included all Danish HIV‐infected patients on highly active antiretroviral therapy (HAART) from 1995 to 2005 (N=2952). Data on hospitalization for MI and comorbidity were obtained from Danish medical databases. Hospitalization rates for MI after HAART initiation were calculated for patients who used abacavir and those who did not. We used Cox's regression to compute incidence rate ratios (IRR) as a measure of relative risk for MI, while controlling for potential confounders (as separate variables and via propensity score) including comorbidity.

Main outcome

Relative risk of hospitalization with MI in abacavir users compared with abacavir nonusers.

Results

Hospitalization rates for MI were 2.4/1000 person‐years (PYR) [95% confidence interval (CI) 1.7–3.4] for abacavir nonusers and 5.7/1000 PYR (95% CI 4.1–7.9) for abacavir users. The risk of MI increased after initiation of abacavir [unadjusted IRR=2.22 (95% CI 1.31–3.76); IRR adjusted for confounders=2.00 (95% CI 1.10–3.64); IRR adjusted for propensity score=2.00 (95% CI 1.07–3.76)]. This effect was also observed among patients initiating abacavir within 2 years after the start of HAART and among patients who started abacavir as part of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen.

Conclusions

We confirmed the association between abacavir use and increased risk of MI. Further studies are needed to control for potential confounding not measured in research to date.
A 12‐month longitudinal study of calcium metabolism and bone turnover during valproate monotherapy
Authors: Verrotti A. , Agostinelli S. , Coppola G. , Parisi P. , Chiarelli F.
Published: August 2009

Background and purpose: Treatment with valproate (VPA) can cause changes in bone mineral metabolism, but the real influences and the underlying pathologic mechanisms are still unclear and under discussion. The aim of this study was to examine the changes on calcium metabolism and bone turnover in post‐pubertal male patients with newly diagnosed idiopathic generalized epilepsy (IGE) before (baseline evaluation) and 12 months after VPA monotherapy (second evaluation).

Methods: Participants included 20 post‐pubertal males with IGE, aged 16.5–22.1 years. Also 20 post‐pubertal sex‐ and age‐matched healthy controls were evaluated. Physical activity, calcium and vitamin D intake were determined. Laboratory samples were obtained to measure biochemical parameters of bone metabolism and bone turnover: serum calcium, phosphate, magnesium, 25‐hydroxyvitamin D, 1,25‐dihydroxyvitamin D, intact parathyroid hormone, total alkaline phosphatase, bone alkaline phosphatase (bone‐ALP), osteocalcin (OC), carboxy‐terminal propeptide of type I procollagen (PICP) and carboxy‐terminal telopeptide of type I collagen (ICTP).

Results: At baseline evaluation, there were no significant differences between controls and patients parameters. At second evaluation, patients showed both markers of bone formation and resorption significantly higher than baseline values (bone‐ALP: 51.2 ± 9.9 vs. 57.3 ± 9.3 U/l,P < 0.01; OC: 8.1 ± 1.1 vs. 10.4 ± 1.5 μg/l,P < 0.01; PICP: 138.7 ± 16.4 vs. 152.6 ± 17.1 μg/l,P < 0.01; ICTP: 3.8 ± 0.8 vs. 5.9 ± 0.6 μg/l,P < 0.01).

Conclusions: Valproate monotherapy in epileptic post‐pubertal males causes a significant increase of bone turnover.
From Intercrisis to Intracrisis Learning
Authors: Moynihan Donald P.
Published: August 2009

This article focuses on collective learning during crises, i.e., intracrisis learning. Intracrisis learning is challenging because decisionmakers must act in a short time frame under conditions of cognitive limitations and political pressure. Intracrisis learning is also complicated by the fact that it usually involves a network of responders, rather than a single organization. The article examines the role of a structural framework, the Incident Command System, in mediating this challenge. The article also describes an example of intracrisis learning, where responders learned from one another, and via virtual experiences, information systems, learning forums, and standard operating procedures.
The potential of probiotic fermented milk products in reducing risk of antibiotic‐associated diarrhoea and Clostridium difficile disease
Authors: LEWIS JONATHAN D N , THOMAS LINDA V , WEIR WILLIAM
Published: August 2009

Currently, the burden of infective antibiotic‐associated diarrhoea (AAD) and Clostridium difficile‐associated disease (CDAD) is placing considerable strain on health services. The potential of probiotics has been investigated, particularly whether they may help reduce the vulnerability of the elderly to these diseases. Probiotic mechanisms of activity include helping to maintain the normal intestinal microbiota and supporting its ability to resist colonisation by pathogens as well as immune modulation. Despite conflicting results from meta‐analyses, there is now increasing evidence that certain Lactobacillus probiotic strains may reduce the risk of AAD and CDAD. Several recent studies report positive results with probiotic‐fermented dairy products.
Cytoprotective effect of polypeptide from Chlamys farreri on neuroblastoma (SH‐SY5Y) cells following H2O2 exposure involves scavenging ROS and inhibition JNK phosphorylation
Authors: Ye Junli , Han Yantao , Wang Chunbo , Yu Wengong
Published: August 2009

Oxidative stress has long been linked to cell death in many neurodegenerative conditions. Treatment with antioxidants is a promising approach for slowing disease progression. In this study, we used the neuroblastoma SH‐SY5Y cells as an in vitro model to first assess the effect of polypeptide from Chlamys farreri (PCF), a natural marine antioxidant, on H2O2‐induced neuronal cell death. Pre‐treatment of SH‐SY5Y cells with PCF inhibited H2O2‐induced cell death in a concentration‐dependent manner. In parallel, intracellular reactive oxygen species generation and lipid peroxidation were inhibited by PCF. Under severe H2O2 insult, PCF promoted endogenous antioxidant defense components including glutathione peroxidase, catalase, superoxide dismutase, and glutathione. PCF also protected DNA from oxidative damage and enhanced the removal of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine from DNA. Further, we found that PCF potentially prevented H2O2–induced cell apoptosis. When investigated mitogen‐activated protein kinase signaling pathway, we found that pre‐treatment of cells with PCF significantly blocked H2O2–induced phosphorylation of c‐Jun N‐terminal kinase of the mitogen‐activated protein kinase family. However, PCF had little inhibitory effect on the H2O2–induced activation of extracellular signal‐regulated kinase. Taken together, these data demonstrate that PCF prevents oxidative stress‐induced reactive oxygen species production and c‐Jun N‐terminal kinase activation and may be useful in the treatment of neurodegenerative diseases.
Penelope’s web: using α‐latrotoxin to untangle the mysteries of exocytosis
Authors: Silva John‐Paul , Suckling Jason , Ushkaryov Yuri
Published: August 2009

For more than three decades, the venom of the black widow spider and its principal active components, latrotoxins, have been used to induce release of neurotransmitters and hormones and to study the mechanisms of exocytosis. Given the complex nature of α‐latrotoxin (α‐LTX) actions, this research has been continuously overshadowed by many enigmas, misconceptions and perpetual changes of the underlying hypotheses. Some of the toxin’s mechanisms of action are still not completely understood. Despite all these difficulties, the extensive work of several generations of neurobiologists has brought about a great deal of fascinating insights into pre‐synaptic processes and has led to the discovery of several novel proteins and synaptic systems. For example, α‐LTX studies have contributed to the widespread acceptance of the vesicular theory of transmitter release. Pre‐synaptic receptors for α‐LTX – neurexins, latrophilins and protein tyrosine phosphatase σ– and their endogenous ligands have now become centrepieces of their own areas of research, with a potential of uncovering new mechanisms of synapse formation and regulation that may have medical implications. However, any future success of α‐LTX research will require a better understanding of this unusual natural tool and a more precise dissection of its multiple mechanisms.
The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice
Authors: Zhu Judy , Xu Wenjing , Wang Jing , Ali Syed F. , Angulo Jesus A.
Published: August 2009

In a previous study we showed that pharmacological blockade of the neurokinin‐1 receptors attenuated the methamphetamine (METH)‐induced toxicity of the striatal dopamine terminals. In the present study we examined the role of the neurokinin‐1 receptors on the METH‐induced apoptosis of some striatal neurons. To that end, we administered a single injection of METH (30 mg/kg, i.p.) to male mice. METH induced the apoptosis (terminal deoxyncleotidyl transferase‐mediated dUTP nick end labeling) of approximately 20% of striatal neurons. This percentage of METH‐induced apoptosis was significantly attenuated by either a single injection of the neurokinin‐1 receptor antagonist, 17‐β‐hydroxy‐17‐a‐ethynyl‐5‐a‐androstano[3,2‐β]pyrimido[1,2‐a]benzimidazole (WIN‐51,708) (5 mg/kg, i.p.), or the ablation of the striatal interneurons expressing the neurokinin‐1 receptors (cholinergic and somatostatin) with the selective neurotoxin [Sar9,Met(O2)11] substance P–saporin. Next we assessed the levels of striatal 3‐nitrotyrosine (3‐NT) by HPLC and immunohistochemistry. METH increased the levels of striatal 3‐NT and this increase was attenuated by pre‐treatment with WIN‐51,708. Our data support the hypothesis that METH‐induced striatal apoptosis occurs via a mechanism involving the neurokinin‐1 receptors and the activation of nitric oxide synthesis. Our findings are relevant for the treatment of METH abuse and may be relevant to certain neurological disorders involving the dopaminergic circuitry of the basal ganglia.
The blood–brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters
Authors: Tachikawa Masanori , Kasai Yasuyuki , Yokoyama Reiji , Fujinawa Jun , Ganapathy Vadivel , Terasaki Tetsuya , Hosoya Ken‐ichi
Published: August 2009

Although the cerebral accumulation of guanidinoacetate (GAA) contributes to neurological complications inS‐adenosylmethionine:guanidinoacetateN‐methyltransferase (GAMT) deficiency, how GAA is abnormally distributed in the brain remains unknown. The purpose of this study was to investigate the transport of GAA across the blood–brain barrier (BBB) and in brain parenchymal cells in rats. [14C]GAA microinjected into the rat cerebrum was not eliminated from the brain, implying the negligible contribution of GAA efflux transport across the BBB. In contrast,in vivoanalysis and an uptake study by TR‐BBB cells, a ratin vitroBBB model, revealed that GAA was transported from the circulating blood across the BBB most likely via a creatine transporter (CRT). Although CRT at the BBB is almost saturated by endogenous creatine under physiological conditions, the creatine level in the blood significantly decreases in GAMT deficiency. This might lead to the increase of CRT‐mediated blood‐to‐brain transport of GAA at the BBB. Furthermore, [14C]GAA was taken up by brain parenchymal cells in a concentrative manner most likely via taurine transporter and CRT. These characteristics of GAA transport across the BBB and in the brain parenchymal cells could be the key factors that facilitate GAA accumulation in the brains of patients with GAMT deficiency.
Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons
Authors: Gandhi Gautam K. , Cruz Nancy F. , Ball Kelly K. , Dienel Gerald A.
Published: August 2009

Brain is a highly‐oxidative organ, but during activation, glycolytic flux is preferentially up‐regulated even though oxygen supply is adequate. The biochemical and cellular basis of metabolic changes during brain activation and the fate of lactate produced within brain are important, unresolved issues central to understanding brain function, brain images, and spectroscopic data. Because in vivo brain imaging studies reveal rapid efflux of labeled glucose metabolites during activation, lactate trafficking among astrocytes and between astrocytes and neurons was examined after devising specific, real‐time, sensitive enzymatic fluorescent assays to measure lactate and glucose levels in single cells in adult rat brain slices. Astrocytes have a 2‐ to 4‐fold faster and higher capacity for lactate uptake from extracellular fluid and for lactate dispersal via the astrocytic syncytium compared to neuronal lactate uptake from extracellular fluid or shuttling of lactate to neurons from neighboring astrocytes. Astrocytes can also supply glucose to neurons as well as glucose can be taken up by neurons from extracellular fluid. Astrocytic networks can provide neuronal fuel and quickly remove lactate from activated glycolytic domains, and the lactate can be dispersed widely throughout the syncytium to endfeet along the vasculature for release to blood or other brain regions via perivascular fluid flow.
Effect of soybean administration on the pharmacokinetics of carbamazepine and omeprazole in rats
Authors: Singh Dharmender , Asad Mohammed
Published: August 2009

Influence of soybean administration on the bioavailability of carbamazepine and omeprazole was studied after single dose administration of soybean (10 g/kg p.o.) or after chronic administration of soybean (50% w/w mixed with normal feed) for 15 days in rats. Carbamazepine was administered orally at a dose of 10 mg/kg and omeprazole at a dose of 20 mg/kg. Soybean decreased the bioavailability of carbamazepine after both single dose and chronic administration. It produced a significant decrease in Cmax, Tmax, AUC0–t of carbamazepine after single dose administration and increased the plasma clearance and Vd along with decrease in Cmax, Tmax, AUC0–t and AUC0–∞ after chronic administration. On the contrary, soybean administration increased the bioavailability of omeprazole by producing an increase in Cmax, AUC0–t and AUC0–∞ and a decrease in Vd after single dose administration and a decrease in plasma clearance along with increase in Cmax, AUC0–t and AUC0–∞ after chronic administration. The half‐life of omeprazole was also increased after both acute and chronic administration of soybean. It was concluded that soybean decreases the bioavailability of carbamazepine and increases the bioavailability of omeprazole after both single dose and chronic administration.
Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta
Authors: Peixoto‐Neves D. , Silva‐Alves K.S. , Gomes M.D.M. , Lima F.C. , Lahlou S. , Magalhães P.J.C. , Ceccatto V.M. , Coelho‐de‐Souza A.N. , Leal‐Cardoso J.H.
Published: August 2009

Various essential oils are rich in carvacrol, a monoterpenic phenol isomeric with thymol. This study was undertaken to assess the vasorelaxant effects of thymol and carvacrol in rat isolated aorta and the putative mechanisms underlying these effects. Thymol and carvacrol produced a concentration‐dependent relaxation on the aortic ring preparations pre‐contracted using KCl (IC50value of 64.40 ± 4.41 and 78.80 ± 11.91 μm, respectively) or using phenylephrine (PHE, 0.1 μm) (IC50value of 106.40 ± 11.37 and 145.40 ± 6.07 μm, respectively) and inhibited the concentration‐response curves of aortic rings to PHE or KCl. In Ca2+‐free medium with ethylene glycol‐bis(2‐aminoethylether)‐N,N,N′,N′‐tetraacetic acid (2 mm), thymol and carvacrol both at 1000 μmcompletely abolished the phasic component of PHE‐induced endothelium‐containing ring contractions. At 400 μm, thymol and carvacrol significantly reduced the CaCl2‐induced contractions in Ca2+‐free medium. Furthermore, both thymol and carvacrol (300 and 1000 μm) significantly reduced the contraction evoked by phorbol dibutyrate (1 μm), an activator of protein kinase C. Magnitude of this inhibitory effect was enhanced in the presence of the Ca2+pump inhibitor, thapsigargin (1 μm). At 1000 μm, neither thymol nor carvacrol altered the resting potential of vascular smooth muscle cells. In conclusion, thymol and carvacrol induced an endothelium‐independent relaxation in rat isolated aorta, an effect that seems mediated through some mechanisms probably involving a transduction pathway between Ca2+release from sarcoplasmic reticulum and/or regulation of the Ca2+sensitivity of the contractile system. Moreover, it’s conceivable that thymol and carvacrol, at low concentrations, block the Ca2+influx through the membrane.
Robert F. Furchgott, Nobel laureate (1916–2009) – a personal reflection
Authors: Martin William
Published: August 2009

Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physiology and stimulated new and exciting opportunities for drug development in a wide range of pathological conditions. In this article, William Martin, who worked with Furchgott for 2 years (1983–1985), following the exciting discovery of endothelium‐derived relaxing factor/nitric oxide, pays tribute to his close friend and colleague.
Inhibition of the JNK signalling pathway enhances proteasome inhibitor‐induced apoptosis of kidney cancer cells by suppression of BAG3 expression
Authors: Wang Hua‐Qin , Liu Bao‐Qin , Gao Yan‐Yan , Meng Xin , Guan Yifu , Zhang Hai‐Yan , Du Zhen‐Xian
Published: August 2009

Background and purpose:  Proteasome inhibitors represent a novel class of anti‐tumour agents that have clinical efficacy against haematological and solid cancers. The anti‐apoptotic protein BAG3 is a member of the Bcl‐2‐associated athanogene family. We have previously shown that BAG3 is up‐regulated after exposure to proteasome inhibitors and that inhibition of BAG3 sensitized cells to apoptosis induced by proteasome inhibition. However, the mechanisms by which proteasome inhibition induced BAG3 expression remained unclear and the present experiments were designed to elucidate these mechanisms.

Experimental approach:  Effects of the proteasome inhibitor MG132 on activation of mitogenic signalling pathways were evaluated in kidney cancer cells (A498, Caki1, Caki2), with Western blotting. Specific inhibitors against individual mitogenic signalling pathways, real‐time reverse transcription‐polymerase chain reaction and luciferase reporter assays were used to investigate the roles of mitogenic signalling pathways in BAG3 induction after proteasome inhibition. Cell death was evaluated using Annexin V/propidium iodide staining and subsequent FACS.

Key results:  MG132 activated several key mitogenic signalling pathways including extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (MAPK) activities. Induction of BAG3 by MG132 was inhibited by blocking JNK, but not ERK1/2 and p38 MAPK signalling pathways. In addition, SP600125 and dominant‐negative JNK1 suppressed BAG3 promoter‐driven reporter gene expression. Furthermore, activation of the JNK pathway induced BAG in kidney cancer cells after treatment with MG132.

Conclusions and implications:  Our results suggested that the JNK pathway was associated with the protective response against proteasome inhibition, by mediating induction of BAG3.
The Epidemiology of Dependence in Older People in Nigeria: Prevalence, Determinants, Informal Care, and Health Service Utilization. A 10/66 Dementia Research Group Cross‐Sectional Survey
Authors: Uwakwe Richard , Ibeh Christian C. , Modebe Anne Ifeoma , Bo Emeka , Ezeama Nkiru , Njelita Ifeoma , Ferri Cleusa P. , Prince Martin J.
Published: August 2009

OBJECTIVES: To describe the prevalence and determinants of dependence in older Nigerians and associations with informal care and health service utilization.

DESIGN: A single‐phase cross‐sectional catchment area survey.

SETTING: Dunukofia, a rural community in southeastern Nigeria.

PARTICIPANTS: One thousand two hundred thirty‐eight adults aged 65 and older, for whom full data were available on 914.

MEASUREMENTS: The full 10/66 Dementia Research Group survey protocol was applied, including ascertainment of depression, cognitive impairment, physical impairments, and self‐reported diagnoses. The interviewer rated dependence as not needing care, needing some care, or needing much care. The prevalence of dependence and the independent contribution of underlying health conditions were estimated. Sources of income, care arrangements, caregiver strain, and health service use are described according to level of dependence.

RESULTS: The prevalence of dependence was 24.3% (95% confidence interval=22.1–26.5%), with a concentration in participants aged 80 and older. Only 1% of participants received a pension, and fewer than 7% had paid work. Those who were dependent were less likely than others to receive income from their family. Cognitive impairment, physical impairments, stroke, and depression were each independently associated with dependence. Depression made the largest contribution. Dependence was strongly associated with health service use (particularly private doctor and traditional healer services) and with high levels of out‐of‐pocket expenditure.

CONCLUSION: In Nigeria, dependence is an important outcome given rapid demographic aging and increases in chronic disease prevalence in all developing regions. Enhancing the social protection of dependent older adults should be a policy priority. Cognitive and mental disorders are important contributors to disability and dependence; more attention should be given to their prevention, detection, and treatment.
Anemia and 9‐Year Domain‐Specific Cognitive Decline in Community‐Dwelling Older Women: The Women's Health and Aging Study II
Authors: Deal Jennifer A. , Carlson Michelle C. , Xue Qian‐Li , Fried Linda P. , Chaves Paulo H. M.
Published: August 2009

OBJECTIVES: To test the hypothesis that anemia (hemoglobin <12 g/dL) is associated with a faster rate of cognitive decline over 9 years in a community‐dwelling sample of women aged 70 to 80 at baseline.

DESIGN: A population‐based, prospective cohort study.

SETTING: East Baltimore, Maryland.

PARTICIPANTS: Four hundred thirty‐six women sampled to be representative of the two‐thirds least‐disabled women aged 70 to 80 at baseline (1994–1996).

MEASUREMENTS: Nine‐year trajectories of cognitive decline, analyzed using linear random effects models, in the domains of immediate verbal recall, delayed verbal recall, psychomotor speed, and executive function.

RESULTS: At baseline and after adjustment for demographic and disease covariates, women with anemia were slower to complete a test of executive function; the difference in baseline function between women with anemia and those without was −0.43 standard deviations (SDs) (95% confidence interval (CI)=−0.74 to −0.13) on the Trail Making Test Part B. During follow‐up, anemia was associated with a faster rate of decline in memory. Between baseline and Year 3, the difference in the rates of decline between women with anemia and those without was −0.18 SDs per year (95% CI=−0.29 to −0.06) on the Hopkins Verbal Learning Test (HVLT) and −0.15 SDs per year (95% CI=−0.26 to −0.04) on the HVLT‐Delayed.

CONCLUSION: Anemia was associated with poorer baseline performance on a test of executive function and with faster rates of decline on tests of immediate and delayed verbal recall. If this relationship is causal, it is possible that treatment of anemia could prevent or postpone cognitive decline.
Association Between Cognitive Function and Social Support with Glycemic Control in Adults with Diabetes Mellitus
Authors: Okura Toru , Heisler Michele , Langa Kenneth M.
Published: August 2009

OBJECTIVES: To examine whether cognitive impairment in adults with diabetes mellitus is associated with worse glycemic control and to assess whether level of social support for diabetes mellitus care modifies this relationship.

DESIGN: Cross‐sectional analysis.

SETTING: The 2003 Health and Retirement Study (HRS) Mail Survey on Diabetes and the 2004 wave of the HRS.

PARTICIPANTS: Adults aged 50 and older with diabetes mellitus in the United States (N=1,097, mean age 69.2).

MEASUREMENTS: Glycosylated hemoglobin (HbA1c) level; cognitive function, measured with the 35‐point HRS cognitive scale (HRS‐cog); sociodemographic variables; duration of diabetes mellitus; depressed mood; social support for diabetes mellitus care; self‐reported knowledge of diabetes mellitus; treatments for diabetes mellitus; components of the Total Illness Burden Index related to diabetes mellitus; and functional limitations.

RESULTS: In an ordered logistic regression model for the three ordinal levels of HbA1c (<7.0, 7.0–7.9, ≥8.0 mg/dL), respondents with HRS‐cog scores in the lowest quartile had significantly higher HbA1c levels than those in the highest cognitive quartile (adjusted odds ratio=1.80, 95% confidence interval=1.11–2.92). A high level of social support for diabetes mellitus care modified this association; for respondents in the lowest cognitive quartile, those with high levels of support had significantly lower odds of having higher HbA1c than those with low levels of support (1.11 vs 2.87, P=.02).

CONCLUSION: Although cognitive impairment was associated with worse glycemic control, higher levels of social support for diabetes mellitus care ameliorated this negative relationship. Identifying the level of social support available to cognitively impaired adults with diabetes mellitus may help to target interventions for better glycemic control.
Baseline and Follow‐Up Characteristics of Participants and Nonparticipants in a Randomized Clinical Trial of Multifactorial Fall Prevention in Denmark
Authors: Vind Ane B. , Andersen Hanne E. , Pedersen Kirsten D. , Jørgensen Torben , Schwarz Peter
Published: August 2009

OBJECTIVES: To address the external validity of a trial of multifactorial fall prevention through an analysis of differences between participants and nonparticipants regarding socioeconomic and morbidity variables.

DESIGN: Analysis of nonresponse in a randomized clinical trial.

SETTING: Geriatric outpatient department.

PARTICIPANTS: One thousand one hundred five community‐dwelling adults aged 65 and older who had sustained at least one injurious fall.

MEASUREMENTS: Marital status, housing tenure, income, comorbidity, hospitalization, fractures, and drug use before invitation to participate in the trial. Fractures, hospitalization and death were measured for 6 months of follow‐up.

RESULTS: Four hundred forty‐seven responding nonparticipants and 266 nonresponding nonparticipants were compared with 392 participants in the trial. Lower income (odds ratio (OR)=2.38, 95% confidence interval (CI)=1.28–4.28) and more days of hospitalization during the previous 5 years (OR=1.96, 95% CI=1.15–3.33) predicted responding nonparticipation; independent predictors of being a nonresponding nonparticipant were unmarried status (OR=2.0, 95% CI=1.36–2.94), lower income (OR=4.74, 95% CI=2.30–9.78), more days of hospitalization (OR=3.49, 95% CI=1.99–6.11), and prior fractures (OR=1.56, 95% CI=1.02–2.38). Nonresponding nonparticipants were significantly more likely to die (OR=12.99, 95% CI=1.6–105.6) or be hospitalized (OR=2.66, 95% CI=1.7–4.1) than participants during 6 months of follow‐up.

CONCLUSION: Nonresponding nonparticipants of a trial of multifactorial fall prevention differed significantly from participants in terms of socioeconomic and morbidity variables and were more likely to be hospitalized or die during 6 months of follow‐up. Because of the differences between the two populations, it is questionable whether results from this randomized trial can be generalized to people potentially eligible for participation.